hospital universitari vall d’ hebron de barcelona

COMPARATIVE STUDY OF THE EFICACY OF

ORAL ADMINISTRATION OF DIACETYLMORPHINE,

MORPHINE AND METHADONE IN MAINTENANCE

TREATMENT OF HEROIN DEPENDENT PATIENTS

WHO HAVE RELAPSED IN METHADONE

MAINTENANCE PROGRAMS

Hospital Universitari Vall d’ Hebron de BarcelonaHospital de la Santa Creu i Sant Pau

Hospital Mútua de Terrassa

Direcció General de Drogodependències i SIDAGeneralitat de Catalunya

• Opioid dependence ( DSM-IV-RT ) smoked or taken intravenously, amongst patients who have been unsuccessful in at least two methadone maintenance programs that lasted a minimum of one month, and in which the dose was equal to or more than 70 mg. of oral methadone per day.

• Active illegal heroin use.

PATHOLOGY IN STUDY

ORAL HEROIN CLINICAL TRIAL

Effectiveness of oral heroin :

- The Swiss project PROVE studied diverse means of heroin administration :

• Intravenous• Smoked• Inhaled• Oral• Suppositories• Transcutaneous


•First clinical trial of a product in clinical research phase ( PEI ) .

•Comparison of three opioid substances in 4 groups:

DESIGN


• Group I : 12 hour controlled release oral

diacetylmorphine.

• Group II : 12 hour controlled release oral morphine.

• Group III : Single dose oral methadone plus placebo.

• Group IV : Double dose oral methadone.

• Clinical Trial Phase III

• Design: Controlled, double blind, in parallel, of 4 randomly

assigned experimental groups .

• Flexible dosePatient

Physician


Length: 6 months

• Induction phase: 14 days hospitilization.

• Maintenance phase: 166 days of outpatient

with 2 daily doses.

DESIGN


• Total number of patients = 180

– Patients per center n = 60

• Diacetylmorphine n = 15

• Morphine n = 15

• Metadone I n = 15

• Metadone II n = 15

DESIGN


X 3

X 3

X 3

X 3

X 3

1.- Subject treatment retention in the study.

2.- Consumption of non - prescribed opioids.

MAIN VARIABLES


SECONDARY OBJECTIVES

•Establish the daily dose of oral diacetylmorphine necessary to bring to completion a maintenance program using this opioid.

•Establish the daily dose of oral morphine necessary to bring to completion a maintenance program using this opioid.



•Establish the equivalence dose between diacetylmorphine and oral methadone in a maintenance program.

•Establish the equivalence dose between oral morphine and oral methadone in a maintenance program.



• Compare the total daily dosage of oral methadone when administered in single dose or in divided doses.

• Compare the dose increment patterns of oral methadone, oral diacetylmorphine, and oral morphine during the course of the trial.

• Compare the presence of concomitant psycho-pathology between the four groups.



• Compare the use of non - opioid psychoactive

substances between groups over the course

of the study.

• Compare the presence of other risk behaviors

between groups during the study.


•Current heroin dependence (physiological), according to DSM-IV-RT criteria, taken orally or smoked, .

•Between 18 and 45 years of age.

•Opioid maintenance treatment is indicated at the present time.

INCLUSION CRITERIA - I -


•Lack of success in at least two Methadone Maintenance Programs. Lack of success is defined as dropping out of a MMP and returning to heroin use. Each of the two MMPs should have been followed for a period of at least one month, with an oral methadone dose of at least 60 mg / day.

•At least one positive urinalysis for opioids, excluding methadone, in the week before the induction phase.

INCLUSION CRITERIA - II -


• Demonstrated capacity to grant and sign the

pertinent informed consent .

• Usual residence compatible with daily attendance

at the dispensing center.

• For women, acceptance of using effective

contraceptive measures during the clinical trial.

INCLUSION CRITERIA - III -


• Pregnancy and natural lactation.

• Serum liser transaminase concentrations 5 times higher than normal.

• Diagnosis of grave physical conditions such as unstable diabetes, active tuberculosis, AIDS (seropositive patients without clinical symptoms can be included), kidney, heart, or renal problems.

EXCLUSION CRITERIA - I -


• Current diagnosis, according to DSM-IV-RT criteria, of the following disorders: Active alcohol, sedative and / or hypnotic dependence, major depression, bipolar disorder, schizophrenia or other psychotic disorders.

• Positive urinalysis for methadone at the outset of the phase prior to treatment induction or following a methadone maintenance program during the previous 30 days.

EXCLUSION CRITERIA - II -


•Prior knowledge of situation that could impede the patient's participation in the trial ( e.g. serving a prison sentence ).

•Current participation in another research project

EXCLUSION CRITERIA - III -


• Current treatment, or the awareness that the patient will initiate treatment during the course of the study, with any of the following medications that could modify the effectiveness of methadone :

– Carbamazepine - Amonium chloride

– Phenobarbitol - Phennitoine

– Rifabutine - Rifampicine

– Eritromicine - Ketoconazol

– Fluconazol - Nevirapine

– Cimetidine

– Antidepresants: MAOS, Tricyclics, fluoxetine, fluvoxamine and paroxetine

– Antirretrovirals protease inhibitors: ritonavir and others.

EXCLUSION CRITERIA - IV -


COMPARATIVE STUDY OF THE EFICACY OF

ORAL ADMINISTRATION OF DIACETYLMORPHINE,

MORPHINE AND METHADONE IN MAINTENANCE

TREATMENT OF HEROIN DEPENDENT PATIENTS

WHO HAVE RELAPSED IN METHADONE

MAINTENANCE PROGRAMS

Hospital Universitari Vall d’ Hebron de BarcelonaHospital de la Santa Creu i Sant Pau

Hospital Mútua de Terrassa

Direcció General de Drogodependències i SIDAGeneralitat de Catalunya

hospital universitari vall d’ hebron de barcelona

Documents

double dose oral methadone

single dose oral methadone

clinical trial phase

maintenance phase

opioid maintenance treatment

equivalence dose

active illegal heroin

clinical research phase