bmj open€¦ · place lucie et raymond aubrac, 63003 clermont-ferrand, france (4) digestive and...

of 112/112
For peer review only Effect of prehabilitation in gastroesophageal adenocarcinoma: study protocol of a multicentric, randomised control trial - PREHAB study Journal: BMJ Open Manuscript ID bmjopen-2016-012876 Article Type: Protocol Date Submitted by the Author: 01-Jun-2016 Complete List of Authors: Le Roy, Bertrand; CHU Estaing, Digestive surgery Pereira, Bruno; University Hospital CHU Clermont-Ferrand, Biostatistic unit Bouteloup, Corinne; CHU Estaing, Digestive and Liver Disease Costes, Frederic; CHU Gabriel Montpied, Department of physiology and medical sport Richard, Ruddy; CHU Gabriel Montpied, Department of physiology and medical sport Selvy, Marie; CHU Estaing, Digestive surgery and oncological department Petorin, Caroline; Oncology Gagniere, Johan; University Hospital of Clermont-Ferrand, Digestive and Hepatobiliary Surgery Futier, Emmanuel; CHU Estaing, Department of Anesthesia Slim, Karem; CHU Estaing, Digestive surgery and oncological department Meunier, Bernard; Centre Hospitalier Universitaire de Rennes Mabrut, Jean-Yves; Hopital de la Croix-Rousse Mariette, C.; CHU Claude Huriez, Digestive and oncological surgery Pezet, Denis; Digestive surgery <b>Primary Subject Heading</b>: Surgery Secondary Subject Heading: Rehabilitation medicine, Oncology Keywords: Prehabilitation, Gastric cancer, Oesophageal disease < GASTROENTEROLOGY, Fitness, Gastrointestinal tumours < ONCOLOGY For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open on July 12, 2020 by guest. Protected by copyright. http://bmjopen.bmj.com/ BMJ Open: first published as 10.1136/bmjopen-2016-012876 on 7 December 2016. Downloaded from

Post on 27-Jun-2020

0 views

Category:

Documents

0 download

Embed Size (px)

TRANSCRIPT

  • For peer review only

    Effect of prehabilitation in gastroesophageal adenocarcinoma: study protocol of a multicentric,

    randomised control trial - PREHAB study

    Journal: BMJ Open

    Manuscript ID bmjopen-2016-012876

    Article Type: Protocol

    Date Submitted by the Author: 01-Jun-2016

    Complete List of Authors: Le Roy, Bertrand; CHU Estaing, Digestive surgery Pereira, Bruno; University Hospital CHU Clermont-Ferrand, Biostatistic unit Bouteloup, Corinne; CHU Estaing, Digestive and Liver Disease

    Costes, Frederic; CHU Gabriel Montpied, Department of physiology and medical sport Richard, Ruddy; CHU Gabriel Montpied, Department of physiology and medical sport Selvy, Marie; CHU Estaing, Digestive surgery and oncological department Petorin, Caroline; Oncology Gagniere, Johan; University Hospital of Clermont-Ferrand, Digestive and Hepatobiliary Surgery Futier, Emmanuel; CHU Estaing, Department of Anesthesia Slim, Karem; CHU Estaing, Digestive surgery and oncological department Meunier, Bernard; Centre Hospitalier Universitaire de Rennes Mabrut, Jean-Yves; Hopital de la Croix-Rousse

    Mariette, C.; CHU Claude Huriez, Digestive and oncological surgery Pezet, Denis; Digestive surgery

    Primary Subject Heading:

    Surgery

    Secondary Subject Heading: Rehabilitation medicine, Oncology

    Keywords: Prehabilitation, Gastric cancer, Oesophageal disease < GASTROENTEROLOGY, Fitness, Gastrointestinal tumours < ONCOLOGY

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open on July 12, 2020 by guest. P

    rotected by copyright.http://bm

    jopen.bmj.com

    /B

    MJ O

    pen: first published as 10.1136/bmjopen-2016-012876 on 7 D

    ecember 2016. D

    ownloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    1

    Effect of prehabilitation in gastroesophageal adenocarcinoma: study protocol of a

    multicentric, randomised control trial - PREHAB study

    Bertrand Le Roy, MD1, Bruno Pereira, PhD

    2, Corinne Bouteloup, MD

    6,9,10, Frederic Costes,

    MD, PhD5, Ruddy Richard, MD, PhD

    5, Marie Selvy, MD

    1, Caroline Pétorin, MD

    1, Johan

    Gagnière, MD1, Emmanuel Futier, MD, PhD

    3, Karem Slim, MD

    1, Bernard Meunier, MD,

    PhD7, Jean-Yves Mabrut, MD, PhD

    8, Christophe Mariette, MD, PhD

    4, Denis Pezet, MD,

    PhD1.

    (1) Digestive surgery and oncological department, Hospital Estaing, 1, place Lucie-Aubrac,

    63003 Clermont-Ferrand, France

    (2) Biostatistics unit (DRCI), Clermont-Ferrand University Hospital, 63003 Clermont-

    Ferrand, France

    (3) Department of Anesthesia, Hospital Estaing, Clermont-Ferrand University Hospital, 1

    Place Lucie et Raymond Aubrac, 63003 Clermont-Ferrand, France

    (4) Digestive and oncological surgery, Hospital Claude Huriez, place de Verdun, 59037 Lille,

    France

    (5) Department of physiology and medical sport, Hospital, Gabriel Montpied, Clermont-

    Ferrand, France

    (6) University Hospital of Clermont-Ferrand, Digestive and Liver Disease Unit F-63003

    Clermont-Ferrand, France

    (7) Digestive surgery department, Hospital Pontchaillou, 2 rue Henri Le Guilloux, 35033

    Rennes, France

    (8) Digestive surgery department, Hospital Croix Rousse, 103 Grande rue de la Croix

    Rousse, 69004 Lyon, France

    (9) Clermont Auvergne University, University of Auvergne, Human Nutrition Unit, ECREIN,

    BP 10448, F-63000 Clermont-Ferrand, France

    (10) INRA, UMR 1019, UNH, CRNH Auvergne, F-63009 Clermont-Ferrand, France

    Corresponding author

    Bertrand Le Roy

    Service de chirurgie et oncologie digestive

    1 place Lucie Aubrac

    Page 1 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    2

    63000 Clermont-Ferrand

    Tel: + 33 4 73 75 04 96

    Email: [email protected]

    Word count: 2840

    Page 2 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    3

    Administrative information

    Title: Effect of prehabilitation in gastroesophageal adenocarcinoma: study protocol of a

    multicentric, randomised control trial - PREHAB study

    Trial registration: NCT02780921

    Protocol version: Version 4, 20 apr 2016

    Funding: This study has received a grant from PHRC (Protocole Hospitalier en Recherche

    Clinique) 2015 (PHRC IR 2015 LE ROY), a national public funding of research.

    In accordance with the Declaration of Helsinki and French regulations on clinical trials, the

    study was presented to an independent ethics committee, the “Comité de Protection des

    Personnes Sud Est 6” (reference: AU1228, IRB00008526, Clermont-Ferrand, France). The

    approval of the committee was obtained on March 7th

    , 2016. The protocol was declared to the

    competent French authority (“Agence Nationale de Sécurité du Médicament et des produits de

    santé”, Saint Denis, France) and registered under number 2015 A01733-46. Authorisation was

    obtained on December, 21st 2015.

    A clinical research assistant will be commissioned by the sponsor (University Hospital of

    Clermont-Ferrand) in order to monitor the progress of the study in accordance with the

    Standard Operating Procedures implemented at the University Hospital of Clermont-Ferrand,

    in accordance with the Good Clinical Practice and current French laws.

    The data set will be the property of the sponsor (CHU Clermont-Ferrand). However, the

    principal investigator and the project manager will have full access to the final data set. The

    results will be communicated in a peer-reviewed journal, presented at international congresses

    and summarized on ClinicalTrials.gov.

    Protocol contributor

    Bertrand Le Roy

    Service de chirurgie et oncologie digestive

    1 place Lucie Aubrac

    63000 Clermont-Ferrand

    Tel: + 33 4 73 75 04 96

    Email: [email protected]

    Study sponsor:

    C.H.U. de Clermont-Ferrand

    58 Rue de Montalembert

    Page 3 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    4

    63003 Clermont-Ferrand Cedex 1

    Protocol contributors

    Pr Christophe Mariette, principal investigator from Lille

    Service de Chirurgie Digestive et Générale

    Hôpital HURIEZ, CHRU Lille

    Place de Verdun, 59037 Lille

    Pr Meunier Bernard, principal investigator from Rennes

    Service de Chirurgie Digestive et Générale

    Hôpital Pontchaillou, CHRU Rennes

    Rue Henri Le Guilloux, 35000 Rennes

    Pr Jean Yves Mabrut, principal investigator from Lyon

    Service de Chirurgie Digestive et Générale

    Hôpital de la Croix Rousse, Hospice civils de Lyon

    Grande rue de la croix rousse, 69317 Lyon

    Contributors: BL, CB, FC, RR, BM, JYM, MS, CP, JG, EF, KS, CM and DP led the

    conceptualisation, design and implementation of this research protocol with the collaboration

    of the FRENCH (Fédération de recherche en chirurgie digestive). BP led the development of

    the statistical analysis plan. BL participated in the design of the protocol for interventions and

    assessments. All the authors have read and approved the final manuscript.

    Page 4 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    5

    ABSTRACT

    Introduction: Perioperative chemotherapy is the gold standard treatment of the resectable

    gastroesophageal adenocarcinoma. However, 70% of patients can’t receive the complete

    sequence because of a postoperative complication or a decrease of functional and nutritional

    reserves. Recently, a new concept appeared in digestive surgery: the prehabilitation. This

    interventional process consists of a patient preparation, between the surgical consultation and

    the surgery, and is based on 3 components: 1) physical management 2) nutritional care and 3)

    psychological care. Prehabilitation should decrease postoperative complications and improve

    nutritional and physical status during the pre- and postoperative period. Therefore, it is

    becoming essential to evaluate the effect of prehabilitation, compared to conventional care, on

    the percentage of patients reaching the complete oncological treatment.

    Methods and analysis: The PREHAB trial aimed to evaluate the efficacy of prehabilitation

    compared to conventional care, in patients with gastroesophageal cancer with perioperative

    chemotherapy. This trial is a prospective, randomised, controlled, open-blind, and

    interventional study, in 4 centers. Patients (n=60 per group) will be randomly assigned for

    management with either prehabilitation or conventional care. The primary outcome is the

    percentage of patients reaching the complete oncological treatment decided in a

    multidisciplinary tumour board. The secondary outcomes are the postoperative morbidity,

    disease free survival, overall survival, feasibility of the protocol, length of stay, variation of

    the functional reserve after the preoperative chemotherapy (defined by VO2peak, ventilatory

    threshold and 6 min walk test), pre- and postoperative nutritional status, preoperative anxiety,

    quality of life, 30- and 90 days mortality and cumulative dose of cytotoxic treatment received.

    Ethics and dissemination: The study was approved by an independent medical ethics

    committee (IRB00008526, CPP Sud-Est VI, Clermont-Ferrand, France) and by the competent

    Page 5 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    6

    French authority (ANSM, Saint Denis, France) and registered on Clinicaltrial.gov. The results

    will be disseminated in a peer-reviewed journal.

    Trial registration number: NCT02780921; pre-result.

    Strengths and limitations of this study: The main strength of this multicentric, prospective

    and randomized study is that this concept of prehabilitation has never been done on this high

    postoperative morbidity surgery. The main limit is this study includes both oesophageal and

    stomach cancer.

    Page 6 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    7

    INTRODUCTION

    Perioperative chemotherapy is the gold standard treatment of the resectable and advanced

    gastroesophageal adenocarcinoma. The efficacy of this strategy has been demonstrated in two

    randomized studies.1 2

    It reduces tumour size before surgery, treats micrometastases and

    evaluates chemosensitivity. Disease free and overall survival rates were significantly

    improved with perioperative chemotherapy compared to surgery alone. However, the

    limitation of these studies is that among all patients requiring chemotherapy, almost 70% of

    patients did not receive the complete sequence. This sequence is defined by the administration

    of two to four cycles before and two to four cycles after the surgery, according to the

    protocol. The major cause of absence or impossibility of realization of postoperative

    chemotherapy was the presence of postoperative complication, postoperative serious asthenia

    and impaired nutritional and physical status. 1 2

    Poor physical condition assessed by

    cardiopulmonary exercise testing, reflecting a reduced physiological reserve, is predictive of

    postoperative complications. 3 4

    A physical training, even during a short period and on a

    various population, is beneficial in improving physical condition, cardiopulmonary function

    and muscular mass of the patient.5-8

    A prehabilitation over a six week period between pre-

    surgical clinic appointment and surgery decreases postoperative morbidity and the hospital

    stay in cardiovascular surgery, but no study has ever been performed in patients presented

    with gastric or oesophageal cancer. 7 9

    Prehabilitation revolves around three axes: 1) a physical training based on initial

    cardiopulmonary exercise testing (VO2peak, ventilatory threshold (VT) and 6-min walk test

    (6MWT)), 3 times by week, supervised by a physical therapist 2) a nutritional care to ensure

    the compliance of the nutrition program and adapt the nutritional management based on

    protein and energy needs and on the level of spontaneous oral intake and 2) a psychological

    treatment by a psychologist to reduce preoperative anxiety. To our knowledge, no study ever

    Page 7 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    8

    focused on the gastroesophageal cancer. The benefit of prehabilitation in this cancer may be

    particularly important because 1) this surgery is associated with a high postoperative

    morbidity (40%, especially respiratory) and mortality (5%) 2) the physical and nutritional

    status of these patients is often precarious (cancer cachexia, gastroesophageal obstruction),

    and 3) the need to preoperative chemotherapy declines physical reserves and is associated

    with a lengthening of the time between pre-surgery clinic appointment and surgery of more

    than 3 months.10

    Also, we hypothesize, in this parallel, of noninferiority study that with a

    physical training, a personalized nutritional support and a psychologist global management

    may decrease postoperative complications, increase postoperative nutritional status and so,

    would results in an increase in the numbers of patients receiving their full cancer treatment.

    The aim of this randomized, with parallel group, of superiority study, was to evaluate, in

    patients presenting with gastroesophageal adenocarcinoma, the effect of prehabilitation

    compared to conventional care, the percentage of patients reaching the complete oncological

    treatment previously decided in a multidisciplinary tumour board.

    METHODS AND ANALYSIS

    Study setting

    The present study is a prospective, randomised, controlled, open and multicentric, phase III

    trial that compares prehabilitation (Prehab group) versus conventional care (control group) in

    patients presenting with gastric and low oesophageal adenocarcinoma, treated by

    perioperative chemotherapy. Inclusions will be perform in four French tertiary centers.

    Study objectives

    In the experimental group (Prehab group), the main objective is to demonstrate an

    improvement of the percentage of patients reaching the complete oncological treatment fixed

    in a multidisciplinary tumour board. The secondary objectives is to evaluate the effect of the

    prehabilitation on the postoperative morbidity according Dindo-Clavien classification, severe

    Page 8 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    9

    morbidity (Clavien >2), disease free survival (DFS), overall survival (OS), feasibility of the

    protocol (number of physical sessions realized on the eighteen proposed), length of stay,

    variation of the functional reserve after the chemotherapy (defined by VO2peak, VT and

    6MWT), pre- and postoperative nutritional status, preoperative anxiety, quality of life (EQ-5D

    survey) at the end of the treatment, 30- and 90 days mortality and cumulative dose of

    cytotoxic treatment received.11

    Inclusion and exclusion criteria

    To be included in the study, the patient must have been operated for a gastric or oesophageal

    adenocarcinoma and received perioperative chemotherapy, subscribe to the French national

    health insurance system and give their written consent. Patients cannot be included in the

    study for one of the following criteria:

  • For peer review only

    10

    Interventions

    After the first visit with his surgeon, the patient will be presented at the multidisciplinary

    tumour board to validate the inclusion criteria and to schedule the number of cycles of pre-

    and postoperative chemotherapy. After this step, a second consultation with the surgeon will

    take place to verify all inclusion and exclusion criteria and perform the randomization. For the

    two groups, an initial (before chemotherapy) and final (one week before the surgery)

    evaluation will be performed. The evaluation includes cardiopulmonary exercise testing

    (VO2peak, VT and 6MWT), nutritional evaluation (albumin), bioelectric impedance analysis,

    evaluation of physical activity and ingesta, evaluation of the level of depressive symptoms

    and anxiety with the HADS survey and the quality of life (5Q-FD survey).

    Study group

    “Prehab” group

    Exercise intervention: The total-body exercise will consist of up to one hour of supervised

    exercise for at least three days per week, for a total of 18 cycles, alternating between aerobic

    and resistance training. Exercise intensity will be prescribed based on the rate of the 6MWT,

    VT and VO2peak. The participant will exercise in the presence of the physical therapist who

    will provide corrective feedback, if necessary.

    Nutrition intervention: Initially, a nutritionist will perform a medical examination run

    appropriate biological tests to evaluate the nutritional status and to provide individualized care

    to each patient. Individual protein requirements will be calculated as 1.2g of protein per

    kilogram of body weight (adjusted body weight was used for obese patients), as per European

    Society for Clinical Nutrition and Metabolism (ESPEN) guidelines regarding surgical

    patients.12

    Patients will be asked to consume the protein supplement within one hour of their

    exercise regimen to capitalize on postexercise muscle protein synthesis.13

    Then, a dietician

    will assess the compliance of the nutritional support at each cycle of chemotherapy and will

    Page 10 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    11

    adjust it, if necessary. After the preoperative chemotherapy, a second evaluation by a

    nutritionist will be performed.

    Psychologist intervention: Patients will receive up to a one hour visit with a trained

    psychologist who will provide techniques aiming to reducing anxiety, such as relaxation

    exercises based on imagery and visualization, together with breathing exercises. Each patient

    will practice these exercises with the psychologist initially and at each cycle of chemotherapy

    and at home two to three times per week. The psychologist also provides suggestions on how

    to enhance and reinforce patients’ motivation to comply with the exercise and nutritional

    aspects of the intervention.

    Control group:

    The control group will be treated according to conventional care; will not receive any specific

    intervention before surgery except nutritional support and physiotherapy at the surgeon’s

    discretion.

    Study outcomes

    The primary outcome is, in patients presenting with gastric or oesophageal adenocarcinoma,

    the percentage of patients in each group, receiving the full perioperative oncological

    treatment, previously defined by a multidisciplinary tumour board. If a patient does not

    complete a chemotherapy course (=event), he will be considered as a subject who did not

    receive the full protocol (chemotherapy-surgery-chemotherapy). However, a decrease in dose

    of chemotherapy or a stop of a component of chemotherapy will not be considered as an

    event.

    The secondary outcomes are: postoperative morbidity at 3 months according Dindo-Clavien

    classification; severe morbidity at 3 months (Clavien >2); disease free survival (DFS),

    survival defined by the time, in months, before recurrence at 3- and 5-years after the end of

    the postoperative chemotherapy; overall survival (OS), defined by the time, in months, of the

    Page 11 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    12

    overall survival at 3- and 5 years after the end of the postoperative chemotherapy; feasibility

    of the protocol defined by the percentage of physical sessions realized on the eighteen

    proposed in the preoperative period; length (in days) of postoperative stay; difference between

    the initial (before preoperative chemotherapy) and final (after preoperative chemotherapy)

    VO2 at the VT (ml.min-1

    .kg-1

    ); difference between the initial (before preoperative

    chemotherapy) and final (after preoperative chemotherapy) value of VO2peak (ml.min-1

    .kg-1

    .);

    difference between the initial (before preoperative chemotherapy) and final (after preoperative

    chemotherapy) 6MWT (meters); difference between the initial (before preoperative

    chemotherapy) and final (after preoperative chemotherapy) weight (Kg); difference between

    the initial (before preoperative chemotherapy) and final (after preoperative chemotherapy)

    albuminemia (g/l); difference between the initial (before preoperative chemotherapy) and

    final (after preoperative chemotherapy) evaluation on the score of HADS survey (Hospital

    anxiety and depression scale) to assess the anxiety and depression from a survey with 14

    questions; difference of the score between the initial evaluation (before preoperative

    chemotherapy) and at 3-months after the surgery of the quality of life defined by the EQ-5D

    survey; 30- and 90 days mortality.

    Methodology and study design

    The trial will be performed in four centres. Patients will be recruited, treated and followed-up

    at the digestive surgery department of the University Hospital of Clermont-Ferrand (France),

    Lille (France), Lyon (France) and Rennes (France). After the multidisciplinary tumour board

    will check all the inclusion and exclusion criteria, the PREHAB trial will be proposed by

    surgeons to patients with gastric or oesophageal adenocarcinoma and concomitant

    perioperative chemotherapy. Patients will be informed of the trial protocol and, on

    acceptance, will be randomised in the “Prehab” group or the control group. Randomisation

    Page 12 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    13

    will be carried out using a dedicated centralised telephone system and accessible round the

    clock. The randomisation sequence will be generated by a biostatistician using random blocks

    and stratification as a function of the centers and type of cancer (œsophagus or stomach). The

    trial will be open blinded because of the procedures employed and with an objective primary

    endpoint. The patient will be informed of the randomisation arm throughout the trial.

    Statistical considerations

    Estimation sample size

    According to previous works, we estimated the percentage of patients in each group, realizing

    the full perioperative oncological treatment around 30% (1,2). A sample size of n=56

    patients by randomized group would provide 90% statistical power to detect an absolute

    difference of 30% (30% vs. 60%) for a two-sided α level of 0.05. Finally, a total of 60

    patients by group will be considered. An interim analysis is planned after enrolment of the

    first 60 patients using the Lan and DeMets, O’Brien-Fleming method (East software, Cytel

    Inc, Cambridge, Massachusetts, USA). The type I error is fixed at 0.003 for this interim

    analysis. The time schedule of enrolment has been estimated at 18 months.

    Statistical analysis

    Statistical analysis will be conducted on intention to treat (ITT) using Stata software, V.13

    (StataCorp, College Station, Texas, USA). A two-sided p value of less than 0.05 will be

    considered to indicate statistical significance (except interim analysis). Baseline

    characteristics will be presented for each randomized group as the mean ± SD or the median

    [interquartile range] according to the statistical distribution for continuous data, and as the

    number of patients and associated percentages for categorical parameters.

    Comparisons between independent groups will be analysed using the χ2 or Fisher's exact test

    for categorical variables (notably unplanned readmission and primary outcome: percentage of

    patients realizing the full perioperative oncological treatment) and Student t-test or Mann-

    Page 13 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    14

    Whitney's test for quantitative parameters (notably weight loss, BMI body mass index,

    albumin, body impedance, length of stay, VO2peak, VT, 6MWT, depressive and anxious

    symptoms evaluated using HADS, quality of Life according EQ-5D). The normality will be

    studied by the Shapiro-Wilk test and the homoscedasticity using the Fisher-Snedecor test. The

    analysis of the primary outcome will be complemented by multivariate analysis using

    generalized linear mixed model (logistic for dichotomous dependent variable) to take into

    account (1) fixed effects covariates retained according to univariate analysis results and

    clinical relevance, and (2) random-effects (between and within centre and surgeon

    variabilities). Censored data such as overall survival or event-free survival will be estimated

    using Kaplan-Meier method and compared (i) by log-rank test in univariate situation and (ii)

    using Cox proportional hazard model in the multivariate context. Regarding the analysis of

    repeated measures, random-effect models (linear or generalised linear) will be considered to

    study the fixed effects group, time-points evaluation and interaction ‘group x time’, taking

    into account between and within subject variability.

    In prehab group, a dose-response study will be proposed to assess (i) the impact of the

    number of prehabilitation sessions really realized and (ii) the compliance prehabilitation care

    (dietary and nutritional management). A particular focus will be done on lost to follow-up. A

    study with the abandonment considered as a censored data will be proposed using Kaplan-

    Meier estimation. If the frequency of missing data is greater than 5%, we will perform

    additional analyses using imputation methods.

    ETHICS AND DISSEMINATION

    Approval

    In accordance with the Declaration of Helsinki and French regulations on clinical trials, the

    study was presented to an independent ethics committee, the “Comité de Protection des

    Page 14 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    15

    Personnes Sud Est 6” (reference: AU1228, IRB00008526, Clermont-Ferrand, France). The

    approval of the committee was obtained on March 7th

    , 2016. The protocol was declared to the

    competent French authority (“Agence Nationale de Sécurité du Médicament et des produits de

    santé”, Saint Denis, France) and registered under number 2015 A01733-46. Authorisation was

    obtained on December, 21st 2015. Any substantial change in the protocol or in the informed

    consent form will be presented to both authorities as well as first inclusion and end of study.

    Data monitoring will be performed per French regulations requirements. As required by the

    IRB, a safety committee has been set up. The study is currently registered on the clinical trials

    website under the following number: NCT02780921. The current protocol version is the firth,

    since April 20th

    , 2016.

    Patient informed consent

    According to international regulations on clinical trials, written informed consent will be

    obtained from patients prior to their participation in the study (Appendices 1 and 2). Patients

    will voluntarily confirm their understanding and willingness to participate in the study after

    having been informed (in writing and verbally) by oncologists on all the aspects of the study.

    They also will be informed about requirements regarding data protection and direct access to

    their individual data. The patients will be informed that they are free to withdraw from the

    study at any time at their own discretion, without necessarily giving reasons.

    Data collection and quality management

    Experienced and trained study coordinators will be dedicated to data acquisition, coding,

    security and storage, under the responsibility of investigators. Each study data will be

    anonymised. Data will be collected and managed using REDCap electronic data capture tools

    hosted at the University Hospital of Clermont-Ferrand.14

    Research Electronic Data Capture

    (REDCap) is a secure, web-based application designed to support data capture for research

    studies, providing: 1) an intuitive interface for validated data entry; 2) audit trails for tracking

    Page 15 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    16

    data handling and export procedures; 3) automated export procedures for seamless data

    downloads to common statistical packages; and 4) procedures for importing data from

    external sources. A clinical research assistant will be commissioned by the sponsor

    (University Hospital of Clermont-Ferrand) in order to monitor the progress of the study in

    accordance with the Standard Operating Procedures implemented at the University Hospital

    of Clermont-Ferrand, in accordance with the Good Clinical Practice and current French laws.

    Access to data and dissemination of results

    The data set will be the property of the sponsor (CHU Clermont-Ferrand). However, the

    principal investigator and the project manager will have full access to the final data set. The

    results will be communicated in a peer-reviewed journal, presented at international congresses

    and summarized on ClinicalTrials.gov.

    DISCUSSION

    The perioperative chemotherapy became the gold standard treatment in advanced gastric and

    low œsophageal adenocarcinoma, with an improvement of DFS and OS.1 2

    However, the

    limitation of these studies is that, among all patients requiring chemotherapy, 70% of patients

    will not receive the complete treatment sequence. In these studies, only patients in good

    nutritional and physical status without postoperative complications can receive postoperative

    treatment. 1 2

    A meta-analysis reported that prehabilitation improved postoperative morbidity,

    length of stay, nutritional and physical status.7 The PREHAB study presented here should

    demonstrate if the prehabilitation increases the percentage of patients reaching the complete

    oncological treatment defined in a multidisciplinary tumour board, to increase DFS and OS.

    Page 16 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    17

    BIBLIOGRAPHY

    1. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJH, Nicolson

    M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal

    cancer. N Engl J Med. 2006 Jul 6;355(1):11–20.

    2. Ychou M, Boige V, Pignon J-P, Conroy T, Bouché O, Lebreton G, et al. Perioperative

    chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma:

    an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol Off J Am Soc Clin Oncol.

    2011 May 1;29(13):1715–21.

    3. Hennis PJ, Meale PM, Grocott MPW. Cardiopulmonary exercise testing for the

    evaluation of perioperative risk in non-cardiopulmonary surgery. Postgrad Med J. 2011

    Aug;87(1030):550–7.

    4. Carlisle J, Swart M. Mid-term survival after abdominal aortic aneurysm surgery

    predicted by cardiopulmonary exercise testing. Br J Surg. 2007 Aug;94(8):966–9.

    5. Fong DYT, Ho JWC, Hui BPH, Lee AM, Macfarlane DJ, Leung SSK, et al. Physical

    activity for cancer survivors: meta-analysis of randomised controlled trials. BMJ.

    2012;344:e70.

    6. Kemi OJ, Wisloff U. High-intensity aerobic exercise training improves the heart in

    health and disease. J Cardiopulm Rehabil Prev. 2010 Feb;30(1):2–11.

    7. Valkenet K, van de Port IGL, Dronkers JJ, de Vries WR, Lindeman E, Backx FJG.

    The effects of preoperative exercise therapy on postoperative outcome: a systematic review.

    Clin Rehabil. 2011 Feb;25(2):99–111.

    8. Jaggers JR, Simpson CD, Frost KL, Quesada PM, Topp RV, Swank AM, et al.

    Prehabilitation before knee arthroplasty increases postsurgical function: a case study. J

    Strength Cond Res Natl Strength Cond Assoc. 2007 May;21(2):632–4.

    9. Van Adrichem EJ, Meulenbroek RL, Plukker JTM, Groen H, van Weert E.

    Page 17 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    18

    Comparison of two preoperative inspiratory muscle training programs to prevent pulmonary

    complications in patients undergoing esophagectomy: a randomized controlled pilot study.

    Ann Surg Oncol. 2014 Jul;21(7):2353–60.

    10. West J, Wood H, Logan RFA, Quinn M, Aithal GP. Trends in the incidence of

    primary liver and biliary tract cancers in England and Wales 1971-2001. Br J Cancer. 2006

    Jun 5;94(11):1751–8.

    11. Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new

    proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004

    Aug;240(2):205–13.

    12. Weimann A, Braga M, Harsanyi L, Laviano A, Ljungqvist O, Soeters P, et al. ESPEN

    Guidelines on Enteral Nutrition: Surgery including organ transplantation. Clin Nutr Edinb

    Scotl. 2006 Apr;25(2):224–44.

    13. Campbell WW, Leidy HJ. Dietary protein and resistance training effects on muscle

    and body composition in older persons. J Am Coll Nutr. 2007 Dec;26(6):696S–703S.

    14. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic

    data capture (REDCap)--a metadata-driven methodology and workflow process for providing

    translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377–81.

    Page 18 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    19

    Contributors: BL, CB, FC, RR, BM, JYM, MS, CP, JG, EF, KS, CM and DP led the

    conceptualisation, design and implementation of this research protocol with the collaboration

    of the FRENCH (Fédération de recherche en chirurgie digestive). BP led the development of

    the statistical analysis plan. BL participated in the design of the protocol for interventions and

    assessments. All the authors have read and approved the final manuscript.

    Funding: This study has received a grant from PHRC (Protocole Hospitalier en Recherche

    Clinique) 2015 (PHRC IR 2015 LE ROY).

    Ethics approval IRB00008526 and ANSM (2015-A01733-46).

    Provenance and peer review Not commissioned; externally peer reviewed.

    Page 19 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    20

    Appendices:

    1. Informed form

    2. Consent form

    Page 20 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    1

    Appendice 1

    FORMULAIRE D’INFORMATION

    Etude pilote, randomisée, multicentrique sur l’effet de la préhabilitation dans le cancer de l’estomac et de

    l’œsophage

    Promoteur de l’essai :

    CHU de Clermont Ferrand,

    58 rue Montalembert,

    63003 Clermont Ferrand Cedex 1, France

    Code promoteur : PHRC IR 2015 LE ROY

    Investigateur coordonnateur :

    Docteur Bertrand Le Roy

    Service de chirurgie digestive et hépato-biliaire

    1 Place Lucie Aubrac

    63003 Clermont-Ferrand

    Madame, Monsieur, il vous est proposé de participer à un protocole de recherche clinique, dont le but

    est de montrer qu’on peut améliorer votre récupération post opératoire et optimiser la poursuite de votre

    traitement de chimiothérapie en vous préparant physiquement, psychologiquement et le plan nutritionnel avant

    l’intervention. Cette prise en charge est appelée « préhabilitation » et va vous être expliquée ci-après plus en

    détails.

    Cependant avant de décider de prendre part à cette étude biomédicale, il est important que vous preniez

    le temps de lire et de comprendre les informations suivantes concernant le déroulement de ce protocole. Cette

    note d’information décrit l’objectif, les procédures, les bénéfices et les risques de l’étude. Elle explique entre

    autre votre droit à vous retirer de l’étude à tout moment sans avoir à vous justifier. S’il y a quoi que ce soit dans

    ce document que vous ne comprenez pas, veuillez demander à votre médecin ("investigateur") ou au personnel

    de l’étude de vous l’expliquer. Prenez votre temps pour décider si vous souhaitez ou non participer à cette étude ;

    parlez-en avec vos amis ou vos proches. Si vous choisissez de participer, il vous sera demandé de signer un

    document intitulé « Formulaire de consentement » et ce en 2 exemplaires, dont un vous sera remis. Si vous

    refusez de prendre part à l’étude, ceci n’aura aucune conséquence sur votre prise en charge médicale.

    Pour pouvoir participer à cette étude vous devez être couvert par un régime de Sécurité Sociale.

    Rationnel de l’étude

    Vous allez être opéré de votre cancer œsogastrique dans le service de chirurgie de votre CHU.

    Comme toute intervention chirurgicale, elle comporte des risques propres à chaque type d’intervention.

    Ces risques peuvent induire une augmentation de votre durée d’hospitalisation, une diminution plus ou moins

    longue de votre qualité de vie voire une impossibilité à poursuivre votre traitement de chimiothérapie.

    Récemment des chirurgiens ont montré qu’une préparation durant 6 semaines avant l’opération, pouvait

    améliorer les résultats post-opératoires sur la morbidité globale, le statut nutritionnel, le retour plus rapide aux

    activités quotidiennes permettant, en autre, de réaliser tout le protocole de chimiothérapie prévu initialement.

    Cette prise en charge est appelée « préhabilitation ». Elle repose sur 3 volets.

    - une prise en charge physique qui consiste à réaliser des exercices cardiovasculaires 3 fois par

    semaine sous surveillance médicale dans le service de médecine du sport et de réadaptation de

    votre l’hôpital

    Paraphe du patient

    Page 21 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    2

    - une prise en charge nutritionnelle qui consiste à établir avec un médecin nutritionniste et un

    diététicien, un programme alimentaire pouvant conduite à une supplémentation nutritionnelle si

    nécessaire

    - une prise en charge psychologique avec le soutien d’un psychologue qui vous recommandera, en

    autre, des tests de relaxation à réaliser à la maison.

    Ce protocole a déjà montré son intérêt dans le domaine de la chirurgie cardio vasculaire ou du cancer colorectal.

    Aussi, nous souhaiterions en faire de même pour la chirurgie du cancer œsogastrique d’où l’étude à laquelle nous

    vous proposons de participer.

    Déroulement de l’étude :

    Après information par votre chirurgien et après lecture de cette note, si vous acceptez de rentrer dans l’étude, un

    bilan pré-opératoire standard pour votre pathologie pourra être réalisé si nécessaire. De même vous pourrez être

    amené à voir ou revoir un anesthésiste à la demande du chirurgien.

    Nous vous demanderons également de bien vouloir compléter, répondre à quelques questionnaires évaluant votre

    qualité de vie, vos habitudes alimentaires, vos activités quotidiennes...

    Après ces évaluations et si vous répondez toujours aux critères du protocole, un tirage au sort sera réalisé afin de

    déterminer dans quel groupe vous allez entrer durant vos séances de chimiothérapie pré opératoire 1) groupe

    contrôle : préparation standard selon les référentiels actuels, 2) groupe préhabilitation.

    Paraphe du patient

    Page 22 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    3

    Paraphe du patient

    Page 23 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    4

    La préparation standard consistera :

    a) à bénéficier de séance de kinésithérapie respiratoire si nécessaire,

    b) à prendre des compléments alimentaires si nécessaire soit par voie orale, soit à l’aide de sonde naso-

    gastrique (sonde qui passe par les narines pour aller directement dans le tube digestif) soit par injection.

    c) à évaluer votre anxiété à l’aide de questionnaires

    La "préhabilitation" consistera :

    a) à réaliser des exercices physiques à raison de 1h, 3 fois par semaine durant 6 semaines dans le service

    de médecine du sport de votre Hôpital et ce, sous la surveillance médicale d’un kinésithérapeute.

    Ces activités seront adaptées à vos propres capacités et selon vos résultats aux examens cardio

    respiratoires réalisés au préalable avant tout traitement. Ils débuteront 2 mois avant votre chirurgie.

    Les exercices réalisés seront de 2 types :

    * des exercices d’endurance dont le but sont d’améliorer votre résistance cardio vasculaire en

    réalisant du vélo et/ou de la marche,

    * des exercices de renforcement musculaires (bras, épaules, poitrine, abdomen, dos hanches et

    jambe) à l’aide de matériel type haltères, élastiques …...

    Tous ces exercices seront actualisés au cours du temps en fonction de vos progrès, performances.

    b) à suivre un programme nutritionnel élaboré avec un nutritionniste 2 mois avant votre chirurgie. Ce

    dernier sera établi en fonction de vos besoins, de vos habitudes alimentaires et pourra être adapté,

    modifié en cours du programme avec l’aide du diététicien qui vous rencontrera régulièrement lors de

    vos

    venues à l’hôpital pour vos séances de chimiothérapie. Vous reverrez également le nutritionniste à la

    fin de vos 6 semaines de préhabilitation.

    c) à vous rendre à des consultations de psychologies pour apprendre à gérer, contrôler votre anxiété, à

    mieux appréhender votre traitement de chimiothérapie et les effets secondaires associés. Pour cela il

    vous sera demandé d’assister à 3 consultations d’1h avec un psychologue qui vous apprendra des

    exercices de relaxations à réaliser ensuite à votre domicile. Ces consultations auront lieu au cours des

    2 mois précédents votre chirurgie

    A la fin de vos séances de chimiothérapie, vous bénéficierez à nouveaux de bilans (et ce, peu importe

    dans quel groupe vous êtes inclus) afin de faire le point sur :

    1) votre résistance cardiorespiratoire

    2) votre état nutritionnel,

    3) votre niveau d’anxiété

    De même il vous sera demandé de répondre à des questionnaires

    Ensuite, un suivi médical 1 mois puis à la fin de votre traitement de chimiothérapie adjuvante sera

    réalisé par le biais d’une consultation afin d’évaluer les suites opératoires, votre qualité de vie, votre autonomie.

    Le déroulement de chaque consultation comprendra un examen médical clinique, des questionnaires spécifiques

    à l’étude à compléter.

    Paraphe du patient

    Page 24 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    5

    Bénéfices et risques de l’étude

    Les bénéfices potentiels pour vous de participer à cette étude pourraient être une meilleure récupération

    post opératoire, une durée d’hospitalisation plus courte et surtout un retour plus rapide à vos activités du

    quotidien, et peut être une meilleur tolérance de la chimiothérapie.

    Ce projet ne devrait pas engendrer de risque supplémentaire pour vous si ce n’est peut être un surplus de

    fatigue liée aux exercices, examens et consultations supplémentaires requis par l’essai, voire des contraintes

    supplémentaires comme disponibilités, déplacements, suivi alimentaire .

    Modalité de recrutement

    Ce protocole sera proposé à 120 patients répondant aux critères d’inclusion et d’exclusion. Ces 120 patients

    seront inclus après signature du consentement éclairé.

    Traitements administrés dans le cadre de cette étude

    Aucun traitement supplémentaire autre que ceux utilisés en routine pour votre prise en charge thérapeutique

    ne sera nécessaire à la conduite de cette étude.

    Evaluations réalisées

    Nous essayerons au mieux de concilier les examens, consultations spécifiques au protocole avec vos venues

    au CHU dans le cadre de votre traitement de chimiothérapie. Si des visites supplémentaires s’avéraient

    nécessaires pour des questions de disponibilités, d’organisation de services sachez que cela n’induire aucun frais

    supplémentaire pour vous.

    De même lors de votre prise en charge, suivi, il vous sera remis des questionnaires permettant d’évaluer

    votre qualité de vie, votre niveau d’anxiété ou encore votre statut physique et nutritionnel. Ces questionnaires

    devront être remplis sur place et prendront au maximum une vingtaine de minutes.

    Durée totale de votre participation à ce protocole

    La durée totale de votre participation à cette étude sera de 6 mois.

    Indemnisation

    Il n’y aura aucune indemnisation dans le cadre de cette étude.

    Période d’exclusion

    La période d’exclusion définie dans le cadre de cette étude est de 15 jours avant votre inclusion jusqu’à

    votre sortie d’étude, période pendant laquelle vous ne pourrez pas participer à un autre protocole de recherche

    clinique.

    Paraphe du patient

    Page 25 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    6

    Conservation de matériel biologique

    Cette étude ne fera l’objet d’aucune conservation de matériel biologique

    Protection des patients et confidentialité

    Cette recherche a reçu l’avis favorable du Comité de Protection des Personnes sud est VI le

    …………………………… ainsi que l’autorisation préalable de l’autorité compétente de santé datée du

    ………………………... Il est possible que cette recherche soit interrompue, si les circonstances le nécessitent,

    par le promoteur ou à la demande de l’autorité de santé.

    Votre participation à cette recherche biomédicale n'engendrera pour vous aucun frais supplémentaire par

    rapport à ceux que vous auriez dans le cadre de la prise en charge standard de votre maladie.

    Toutefois, pour pouvoir participer à cette recherche vous devez être affilié(e) ou bénéficier d’un régime de

    sécurité sociale.

    Le CHU de Clermont-Ferrand, qui organise cette recherche biomédicale en qualité de promoteur, a

    contracté une assurance conformément aux dispositions législatives, garantissant sa responsabilité civile et celle

    de tout intervenant auprès de la Société Hospitalière d’Assurances Mutuelles (SHAM, contrat n° 147161). Dans

    le cas où votre état de santé serait altéré du fait de votre participation à l’étude, conformément à la loi de Santé

    Publique n°2004-806 du 9 août 2004, vous seriez en droit de recevoir des dédommagements dans le cadre de ce

    contrat d’assurance spécifique.

    Dans le cadre de la recherche biomédicale à laquelle le CHU de Clermont-Ferrand (établissement

    promoteur) vous propose de participer, un traitement informatique de vos données personnelles va être mis en

    œuvre pour permettre d’analyser les résultats de la recherche au regard de l’objectif de cette dernière qui vous a

    été présenté. A cette fin, les données médicales vous concernant et les données relatives à vos habitudes de vie,

    seront transmises au Promoteur de la recherche ou aux personnes ou sociétés agissant pour son compte, en

    France ou à l’étranger. Ces données seront identifiées par un numéro de code et par vos initiales. Ces données

    pourront également, dans des conditions assurant leur confidentialité, être transmises aux autorités de santé

    françaises, à d’autres entités du CHU de Clermont Ferrand (établissement promoteur).

    Conformément aux dispositions de loi relative à l’informatique aux fichiers et aux libertés, vous disposez

    d’un droit d’accès et de rectification. Vous disposez également d’un droit d’opposition à la transmission des

    données couvertes par le secret professionnel susceptibles d’être utilisées dans le cadre de cette recherche et

    d’être traitées.

    Vous pouvez également accéder directement ou par l’intermédiaire d’un médecin de votre choix à

    l’ensemble de vos données médicales en application des dispositions de l’article L. 1111-7 du code de la santé

    publique. Ces droits s’exercent auprès du médecin qui vous suit dans le cadre de la recherche et qui connaît votre

    identité.

    Par ailleurs, vous pourrez être tenu informé des résultats globaux de cette recherche à la fin de l’étude.

    Vous êtes libre d'accepter ou de refuser de participer à cette recherche. De plus vous pouvez exercer à tout

    moment votre droit de retrait de cette recherche sans avoir à vous justifier. Le fait de ne plus participer à cette

    recherche ne modifiera pas la qualité des soins qui vous sont prodigués. Vous pouvez demander à tout moment

    des explications complémentaires sur l’étude à l’équipe soignante.

    Lorsque vous aurez lu cette note d’information et obtenu les réponses aux questions que vous vous posez

    en interrogeant le médecin investigateur, il vous sera proposé, si vous en êtes d’accord,

    Paraphe du patient

    Page 26 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    7

    de donner votre consentement écrit en signant le document préparé à cet effet en accord avec le code de la

    santé publique visant à protéger les personnes se soumettant à une étude biomédicale. Votre consentement écrit

    n’enlève en aucun cas la responsabilité des médecins qui vous soignent

    A qui devez-vous vous adresser en cas de questions ou de problèmes ?

    En cas de problèmes, d’événements indésirables en cours d’essai ou de questions, vous pouvez vous

    adresser aux personnes suivantes :

    Vos contacts dans l’étude

    Bertrand Le Roy (Coordonnateur)

    Service de Chirurgie Digestive Hôpital Estaing CHU de Clermont-Ferrand

    1 place Lucie et Raymond Aubrac 63003 Clermont-Ferrand cedex 1

    Tel: 04 73 75 04 94 Fax : 04 73 75 19 22 [email protected]

    clermontferrand.fr

    Brigitte Gillet (Ingénieur Hospitalier, Attaché de recherche clinique)

    Service de Chirurgie Digestive Unité d'Oncologie Digestive Hôpital Estaing

    CHU de Clermont-Ferrand 1 place Lucie et Raymond Aubrac

    63003 Clermont-Ferrand cedex 1Tel: 04 73 75 52 26 Fax : 04 73 75 19 22 [email protected]

    clermontferrand.fr

    Paraphe du patient sur toutes les pages

    Date : ……/……/……

    Signature du patient Paraphe de l’investigateur

    (Précédée de la mention « Lu et compris »)

    Page 27 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    8

    Appendice 2

    FORMULAIRE DE CONSENTEMENT DE PARTICIPATION A UNE

    RECHERCHE BIOMEDICALE

    Etude pilote, randomisée, multicentrique sur l’effet de la préhabilitation

    dans le cancer de l’œsophage et de l’estomac

    Promoteur de l’essai :

    CHU de Clermont Ferrand,

    58 rue Montalembert,

    63003 Clermont Ferrand Cedex 1, France

    Code promoteur : PHRC IR 2015 LE ROY

    Investigateur coordonnateur :

    Docteur Bertrand Le Roy

    Service de chirurgie digestive et hépato-biliaire

    1 Place Lucie Aubrac

    63003 Clermont-Ferrand

    Je soussigné(e)

    Mme, M

    lle, M. (rayer les mentions inutiles) (nom, prénom)……………………………………………

    Né(e) le ………………….…………………...

    Déclare :

    - que le Docteur (nom, prénom, téléphone) ……………………………………………..…………….. m’a proposé

    de participer à l’étude sus nommée,

    - qu’il m’a expliqué en détail le protocole,

    - qu’il m’a notamment fait connaître :

    • l’objectif, la méthode et la durée de l’étude

    • les contraintes et les risques potentiels encourus

    • mon droit de refuser de participer et en cas de désaccord de retirer mon consentement à tout moment

    • mon obligation d’inscription à un régime de sécurité sociale

    • que, si je le souhaite, à son terme, je serais informé(e) par le médecin investigateur de ses résultats globaux

    • que je ne serais pas autorisé(e) à participer à d’autres études cliniques durant toute ma participation à ce

    protocole estimée à 6 mois maximum.

    • que le Comité de Protection des Personnes Sud Est VI a émis un avis favorable en date du

    xx/xx/xxxx(Préciser le nom de CPP sollicité et la date d’obtention de l’avis favorable)

    • que l’ANSM (Agence Nationale de Sécurité du Médicament et des produits de santé) a délivré une

    autorisation pour cette étude

    • que dans le cadre de cette étude le promoteur, le CHU de Clermont-Ferrand, a souscrit à une assurance

    couvrant cette recherche (contrat SHAM 147161).

    - que j’ai répondu en toute bonne foi aux questions concernant mon état de santé et ma participation à d’autres

    études.

    Les informations relatives à l’étude recueillies par l’investigateur sont traitées confidentiellement. J’accepte que

    les données enregistrées à l’occasion de cette recherche puissent faire l’objet d’un traitement informatisé

    anonyme. J’ai bien noté que le droit d’accès prévu par la loi du 6 août 2004 relative à l’informatique, aux fichiers

    et aux libertés s’exerce à tout moment auprès du médecin qui me suit dans le cadre de la recherche et qui connaît

    mon identité. Je pourrai exercer mon droit de rectification et d’opposition auprès de ce même médecin, qui

    contactera le promoteur de la recherche

    Page 28 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    9

    Après avoir discuté librement et obtenu réponse à toutes mes questions, j’accepte librement et

    volontairement de participer à cette recherche biomédicale dans les conditions précisées dans le

    formulaire d’information et de consentement.

    Nom et prénom du patient :

    ……………………………………………………

    Date :……./……./…….

    Signature

    Précédée de la mention « Lu et compris » :

    Nom de l’investigateur :

    ……………………………………………………

    Date :……./……./…….

    Signature :

    Ce document est à réaliser en 2 exemplaires originaux, dont le premier doit être gardé 15 ans par l’investigateur,

    un autre remis à la personne donnant son consentement.

    Page 29 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    Spirit

    Administrative information

    Title

    1

    Descriptive title identifying the study design, population, interventions, and, if applicable, trial acronym

    Trial registration=> Page 3

    2a

    Trial identifier and registry name. If not yet registered, name of intended registry

    => Page 3

    2b

    All items from the World Health Organization Trial Registration Data Set

    Protocol version

    => Page 3

    3

    Date and version identifier

    Funding

    => Page 3

    4

    Sources and types of financial, material, and other support

    Roles and responsibilities

    => Page 3-4

    5a

    Names, affiliations, and roles of protocol contributors

    => Page 4

    5b

    Name and contact information for the trial sponsor

    => Page 3-4

    5c

    Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation

    of data; writing of the report; and the decision to submit the report for publication, including whether they will

    have ultimate authority over any of these activities

    => Page 3

    5d

    Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication

    committee, data management team, and other individuals or groups overseeing the trial, if applicable (see

    Item 21a for data monitoring committee)

    => Page 3

    Introduction

    Background and rationale

    6a

    Description of research question and justification for undertaking the trial, including summary of relevant

    studies (published and unpublished) examining benefits and harms for each intervention

    => Page 7

    Page 30 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    6b

    Explanation for choice of comparators

    => Page 8

    Objectives

    7

    Specific objectives or hypotheses

    Trial design

    => Page 8

    8

    Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation

    ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory)

    => Page 8

    Methods: Participants, interventions, and outcomes

    Study setting

    9

    Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be

    collected. Reference to where list of study sites can be obtained Eligibility criteria

    => Page 8

    10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and

    individuals who will perform the interventions (eg, surgeons, psychotherapists) Interventions

    => Page 9

    11a Interventions for each group with sufficient detail to allow replication, including how and when they will be

    administered

    => Page 10

    11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose

    change in response to harms, participant request, or improving/worsening disease)

    => Page 11-12

    11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence

    (eg, drug tablet return, laboratory tests)

    => Page 11-12

    11d Relevant concomitant care and interventions that are permitted or prohibited during the trial Outcomes

    => Page 11-12

    12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood

    pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg,

    median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy

    and harm outcomes is strongly recommended Participant timeline

    => Page 11-12

    13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for

    participants. A schematic diagram is highly recommended (see Figure) Sample size

    => Page 13-14

    Page 31 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    14 Estimated number of participants needed to achieve study objectives and how it was determined, including

    clinical and statistical assumptions supporting any sample size calculations Recruitment

    => Page 13-14

    15 Strategies for achieving adequate participant enrolment to reach target sample size

    => Page 14

    Methods: Assignment of interventions (for controlled trials) Allocation: Sequence generation

    16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any

    factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg,

    blocking) should be provided in a separate document that is unavailable to those who enrol participants or

    assign interventions

    => Page 14

    Allocation concealment mechanism

    16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered,

    opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned

    Implementation

    => Page 14

    16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to

    interventions Blinding (masking)

    => Page 14

    17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome

    assessors, data analysts), and how

    => Page 14

    17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant’s

    allocated intervention during the trial Methods: Data collection, management, and analysis Data collection

    methods

    => NA

    18a Plans for assessment and collection of outcome, baseline, and other trial data, including any related

    processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of

    study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known.

    Reference to where data collection forms can be found, if not in the protocol

    => Page 14

    18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be

    collected for participants who discontinue or deviate from intervention protocols Data management

    => Page 14

    19 Plans for data entry, coding, security, and storage, including any related processes to promote data quality

    (eg, double data entry; range checks for data values). Reference to where details of data management

    procedures can be found, if not in the protocol Statistical methods

    => Page 14

    Page 32 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    20a Statistical methods for analysing primary and secondary outcomes. Reference to where other details of the

    statistical analysis plan can be found, if not in the protocol

    => Page 14

    20b Methods for any additional analyses (eg, subgroup and adjusted analyses)

    => Page 14

    20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any

    statistical methods to handle missing data (eg, multiple imputation)

    => Page 14

    Methods:

    Monitoring Data monitoring

    21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement

    of whether it is independent from the sponsor and competing interests; and reference to where further details

    about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed

    => Page 16

    21b Description of any interim analyses and stopping guidelines, including who will have access to these

    interim results and make the final decision to terminate the trial Harms

    => Page 13

    22 Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse

    events and other unintended effects of trial interventions or trial conduct Auditing

    => Page 13

    23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent

    from investigators and the sponsor

    => Page 13

    Ethics and dissemination

    Research ethics approval

    24

    Plans for seeking research ethics committee/institutional review board (REC/IRB) approval

    Protocol amendments

    => Page 14-15

    25

    Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes,

    analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals, regulators)

    => Page 14-15

    Consent or assent

    26a

    Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and how

    (see Item 32)

    => Page 15

    26b

    Additional consent provisions for collection and use of participant data and biological specimens in ancillary

    studies, if applicable

    Confidentiality

    Page 33 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    => Page 15

    27

    How personal information about potential and enrolled participants will be collected, shared, and maintained

    in order to protect confidentiality before, during, and after the trial

    Declaration of interests

    28

    Financial and other competing interests for principal investigators for the overall trial and each study site

    Access to data

    29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that

    limit such access for investigators Ancillary and post-trial care

    30 Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial

    participation

    Dissemination policy

    => Page 16

    31a

    Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals, the

    public, and other relevant groups (eg, via publication, reporting in results databases, or other data sharing

    arrangements), including any publication restrictions

    => Page 16

    31b

    Authorship eligibility guidelines and any intended use of professional writers

    => Page 16

    31c

    Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code

    => Page 16

    Appendices

    Informed consent materials

    32

    Model consent form and other related documentation given to participants and authorised surrogates

    Biological specimens

    => Appendice 1, legends page 20

    33

    Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis

    in the current trial and for future use in ancillary studies, if applicable

    =>NA

    Page 34 of 34

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    Effect of prehabilitation in gastroesophageal adenocarcinoma: study protocol of a multicentric,

    randomised control trial - PREHAB study

    Journal: BMJ Open

    Manuscript ID bmjopen-2016-012876.R1

    Article Type: Protocol

    Date Submitted by the Author: 14-Sep-2016

    Complete List of Authors: Le Roy, Bertrand; CHU Estaing, Digestive surgery Pereira, Bruno; University Hospital CHU Clermont-Ferrand, Biostatistic unit Bouteloup, Corinne; CHU Estaing, Digestive and Liver Disease

    Costes, Frederic; CHU Gabriel Montpied, Department of physiology and medical sport Richard, Ruddy; CHU Gabriel Montpied, Department of physiology and medical sport Selvy, Marie; CHU Estaing, Digestive surgery and oncological department Petorin, Caroline; Oncology Gagniere, Johan; University Hospital of Clermont-Ferrand, Digestive and Hepatobiliary Surgery Futier, Emmanuel; CHU Estaing, Department of Anesthesia Slim, Karem; CHU Estaing, Digestive surgery and oncological department Meunier, Bernard; Centre Hospitalier Universitaire de Rennes Mabrut, Jean-Yves; Hopital de la Croix-Rousse

    Mariette, C.; CHU Claude Huriez, Digestive and oncological surgery Pezet, Denis; Digestive surgery

    Primary Subject Heading:

    Surgery

    Secondary Subject Heading: Rehabilitation medicine, Oncology

    Keywords: Prehabilitation, Gastric cancer, Oesophageal disease < GASTROENTEROLOGY, Fitness, Gastrointestinal tumours < ONCOLOGY

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open on July 12, 2020 by guest. P

    rotected by copyright.http://bm

    jopen.bmj.com

    /B

    MJ O

    pen: first published as 10.1136/bmjopen-2016-012876 on 7 D

    ecember 2016. D

    ownloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    1

    Effect of prehabilitation in gastroesophageal adenocarcinoma: study protocol of a

    multicentric, randomised control trial - PREHAB study

    Bertrand Le Roy, MD1, Bruno Pereira, PhD

    2, Corinne Bouteloup, MD

    6,9,10, Frédéric Costes,

    MD, PhD5,10

    , Ruddy Richard, MD, PhD5,10

    , Marie Selvy, MD1, Caroline Pétorin, MD

    1, Johan

    Gagnière, MD1, Emmanuel Futier, MD, PhD

    3, Karem Slim, MD

    1, Bernard Meunier, MD,

    PhD7, Jean-Yves Mabrut, MD, PhD

    8, Christophe Mariette, MD, PhD

    4, Denis Pezet, MD,

    PhD1.

    (1) Digestive surgery and oncological department, Hospital Estaing, 1, place Lucie-Aubrac,

    63003 Clermont-Ferrand, France

    (2) Biostatistics unit (DRCI), Clermont-Ferrand University Hospital, 63003 Clermont-

    Ferrand, France

    (3) Department of Anesthesia, Hospital Estaing, Clermont-Ferrand University Hospital, 1

    Place Lucie et Raymond Aubrac, 63003 Clermont-Ferrand, France

    (4) Digestive and oncological surgery, Hospital Claude Huriez, place de Verdun, 59037 Lille,

    France

    (5) Department of Sports Medicine and Functional Explorations, Hospital, Gabriel Montpied,

    Clermont-Ferrand, France

    (6) University Hospital of Clermont-Ferrand, Digestive and Liver Disease Unit F-63003

    Clermont-Ferrand, France

    (7) Digestive surgery department, Hospital Pontchaillou, 2 rue Henri Le Guilloux, 35033

    Rennes, France

    (8) Digestive surgery department, Hospital Croix Rousse, 103 Grande rue de la Croix

    Rousse, 69004 Lyon, France

    (9) Clermont Auvergne University, University of Auvergne, Human Nutrition Unit, ECREIN,

    BP 10448, F-63000 Clermont-Ferrand, France

    (10) INRA, UMR 1019, UNH, CRNH Auvergne, F-63009 Clermont-Ferrand, France

    Corresponding author

    Bertrand Le Roy

    Service de chirurgie et oncologie digestive

    1 place Lucie Aubrac

    Page 1 of 36

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    2

    63000 Clermont-Ferrand

    Tel: + 33 4 73 75 04 96

    Email: [email protected]

    Word count: 2840

    Page 2 of 36

    For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

    BMJ Open

    123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

    on July 12, 2020 by guest. Protected by copyright.

    http://bmjopen.bm

    j.com/

    BM

    J Open: first published as 10.1136/bm

    jopen-2016-012876 on 7 Decem

    ber 2016. Dow

    nloaded from

    http://bmjopen.bmj.com/

  • For peer review only

    3

    Administrative information

    Title: Effect of prehabilitation in gastroesophageal adenocarcinoma: study protocol of a

    multicentric, randomised control trial - PREHAB study

    Trial registration: NCT02780921

    Protocol version: Version 4, 20 apr 2016

    Funding: This study has received a grant from PHRC (Protocole Hospitalier en Recherche

    Clinique) 2015 (PHRC IR 2015 LE ROY), a national public funding of research.

    In accordance with the Declaration of Helsinki and French regulations on clinical trials, the

    study was presented to an independent ethics committee, the “Comité de Protection des

    Personnes Sud Est 6” (reference: AU1228, I