The SToP-BPD study

Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants

Initiation visit

Content• General introduction • Website• Randomization procedure• Medication schedule

– What to do at the occurence of hypertension– Prophylactic stress medication

• Rescue therapy• SUSAR procedure • Discharge from level III hospital

– with study medication?

• BPD diagnosis/Oxygen reduction test

Purpose of the study

• To investigate whether hydrocortisone, initiated 7-14 d after birth reduces the combined outcome death or BPD at 36 wks PMA

• To investigate whether a potential beneficial effect on BPD is not at the cause of (inacceptable) adverse effects

Inclusion criteria

• GA < 30 wks and/or BW < 1250 g• Ventilator dependent between 7-14 days PNA• RI (MAwP x FiO2) ≥ 3.5• RI during > 12 h/dy and for > 48 uur• Targets SpO2 85-95% / pCO2 of 5.0-7.5 kPa

– targets only for calculating RI, after inclusion according to local protocol!

Exclusion criteria

• Chromosomal defects• Major congenital malformations that:

– compromise lung function (SP def., hernia) – result in chronic ventilation (e.g. Pierre Robin

sequence)• Congenital cerebral malformations• Use of steroids for improving lung function

and respiratory status prior to inclusion

No strict exclusion criteria

• Sepsis and/or pneumonia – Await the effect of antibiotica 48 uur

• Hemodynamic significant ODB – Preferable screening 7 dy and treating

according to local protocol– Attempt not to use indo/ibu en HC

simultanuous

Randomization

• Possible between 7-14 days PNA• Hydrocortison or placebo 22 dys• First dose within 24 hours after inclusion• Web-based randomization• Stratification according to center and GA• Twin may be allocated to the same arm

– Procedure on the website

Website on www.neonatologiestudies.nl

(NNRN)

eCRF

• Website• E-learning• Guideline

SToP-BPD

eCRF layout

• Screening & Eligibility• Randomization (twins) • Visits

– Daily reports• Conditions

– Range– Validation– Derivation

Print out Daily reports

Medication

HC course

• Hydrocortison Pharmachemie (100 mg/ml)• Cumul. dose 72,5 mg/kg (=2.5 mg/kg dexa):

– 5 mg/kg/d in 4xday during 7 dys– 3,75 mg/kg/d in 3xday during 5 dys– 2,5 mg/kg/d in 2xday during 5 dys– -1,25 mg/kg/d in 1xday during 5 dys

• Total duration 22 days

Placebo course

• ACE pharmaceuticals Zeewolde, NL• Mannitol as base (pH en Osmol identical to

HC)• Same concentration/dose as HC• On the shelf stable for 3 years

Study medication

• Transported via AMC, delivered in badges of 10 pieces

• Issue locally by the pharmacy (per patient or per badge)

• Stock will be automattically suplemented according to use

• Medication kit contains of 23 vials

Study medication

• After randomization a medication order can be printed from the website

Study medication

• Preparation protocol• Diluent from own stock• Preparation of medication per dag• Medication recorded on drug

accountability form

Medication schedule

Details medication

• Occurring of hypertension• Prophylactic stress medication

Go to website/protocol

Rescue therapy

Treatment failure of vroege rescue

• Reason for considering open label rescue:– deterioration with RI>10 for >6 uur– no improvement (RI<10) and:

• At least 10 dys study medication• Attempt to extubate failed < 24 hrs

• Rescue with HC according to study schedule and stop study medication

Late rescue treatment

• Patient still ventilator dependent after 22 d• Attempt to extubate failed• Late rescue possible with HC according to

study protocol

Safety and reportingAE/SAE/SUSAR

• AE: Any undesirable experience occurring to a subject duringthis trial, whether or not considered related to the investigational.

• An AE is a SAE if:– Resulted in death– Life-threatening– Required (prolongation of existing)

hospitalisation – Persistent or significant disability/incapacity– Another important medical condition

Context-specific SAEs

• Study population at high risk of serious complications,– inherent to their vulnerable condition – unrelated to the intervention which is under evaluation

• Endpoints of the study in the CRF

• Immediate reporting of these complications will not enhance the safety of this trial

• Reporting of these events to the DMC and METC on a annual basis.

Suspected (Unexpected) Serious Adverse Reactions (SUSAR)

• SUSAR : adverse reactions, of which the nature, or severity, is not consistent with the applicable product information or the context-specific SAEs as listed above.

• Reporting < 24 hrs on AE page of CRF and by telephone to the PI

Web-based Alert procedure

Alert Procedure (automated email to stop-bpd@amc.nl) should be used with

• Death

• Simultanuous treatment of indomethacine/ibuprofen and study medication

• Occurrence of solitair gastointestinal perforation

• Occurence of hypertension, as defined in the protocol

• Use of open label hydrocortisone

Reporting should be done < 72 hrs of the occurence of the event.

Discharge from level III hospital

• Letter for general pediatrician on the website

Oxygen reduction test

• Criteria: only O2 defined

• Depending on saturation targets or other diseases

• Practical guideline on the website

Logistics oxygen reduction test

• Local?– Familiair with reduction test– Training of local pediatricians

• Regional?– Research nurse?– Recording?

Vragen?