Hospital Universitari Vall d’ Hebron de Barcelona
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Transcript of Hospital Universitari Vall d’ Hebron de Barcelona
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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
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• 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
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Effectiveness of oral heroin :
- The Swiss project PROVE studied diverse means of heroin administration :
• Intravenous• Smoked• Inhaled• Oral• Suppositories• Transcutaneous
ORAL HEROIN CLINICAL TRIAL
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•First clinical trial of a product in clinical research phase ( PEI ) .
•Comparison of three opioid substances in 4 groups:
DESIGN
ORAL HEROIN CLINICAL TRIAL
• 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.
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• Clinical Trial Phase III
• Design: Controlled, double blind, in parallel, of 4 randomly
assigned experimental groups .
• Flexible dosePatient
Physician
ORAL HEROIN CLINICAL TRIAL
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Length: 6 months
• Induction phase: 14 days hospitilization.
• Maintenance phase: 166 days of outpatient
with 2 daily doses.
DESIGN
ORAL HEROIN CLINICAL TRIAL
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• 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
ORAL HEROIN CLINICAL TRIAL
X 3
X 3
X 3
X 3
X 3
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1.- Subject treatment retention in the study.
2.- Consumption of non - prescribed opioids.
MAIN VARIABLES
ORAL HEROIN CLINICAL TRIAL
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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.
ORAL HEROIN CLINICAL TRIAL
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SECONDARY OBJECTIVES
•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.
ORAL HEROIN CLINICAL TRIAL
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SECONDARY OBJECTIVES
• 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.
ORAL HEROIN CLINICAL TRIAL
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SECONDARY OBJECTIVES
• 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.
ORAL HEROIN CLINICAL TRIAL
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•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 -
ORAL HEROIN CLINICAL TRIAL
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•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 -
ORAL HEROIN CLINICAL TRIAL
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• 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 -
ORAL HEROIN CLINICAL TRIAL
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• 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 -
ORAL HEROIN CLINICAL TRIAL
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• 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 -
ORAL HEROIN CLINICAL TRIAL
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•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 -
ORAL HEROIN CLINICAL TRIAL
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• 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 -
ORAL HEROIN CLINICAL TRIAL
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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