Download M. Casas (Barcelona, Spain)

Direcció General de Drogodependències i SIDA
Generalitat de Catalunya
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 Barcelona
Hospital de la Santa Creu i Sant Pau
Hospital Mútua de Terrassa
ORAL HEROIN CLINICAL TRIAL
PATHOLOGY IN STUDY
• 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.
ORAL HEROIN CLINICAL TRIAL
Effectiveness of oral heroin :
- The Swiss project PROVE studied
means of heroin administration :
•
•
•
•
•
•
Intravenous
Smoked
Inhaled
Oral
Suppositories
Transcutaneous
diverse
ORAL HEROIN CLINICAL TRIAL
DESIGN
• First clinical trial of
research phase ( PEI ) .
a
product
in
clinical
• Comparison of three opioid substances in 4 groups:
• 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.
ORAL HEROIN CLINICAL TRIAL
• Clinical Trial Phase III
• Design:
Controlled, double blind,
in parallel, of 4 randomly
assigned experimental
groups .
• Flexible dose
Patient
Physician
ORAL HEROIN CLINICAL TRIAL
DESIGN
Length: 6 months
• Induction phase:
14 days hospitilization.
• Maintenance phase:
166 days of outpatient
with 2 daily doses.
ORAL HEROIN CLINICAL TRIAL
DESIGN
• Total number of patients = 180
– Patients per center
• Diacetylmorphine
• Morphine
• Metadone I
• Metadone II
n = 60
X3
n = 15 X 3
n = 15 X 3
n = 15 X 3
n = 15 X 3
ORAL HEROIN CLINICAL TRIAL
MAIN VARIABLES
1.- Subject treatment retention in the study.
2.- Consumption of non - prescribed opioids.
ORAL HEROIN CLINICAL TRIAL
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
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
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 psychopathology between the four groups.
ORAL HEROIN CLINICAL TRIAL
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
INCLUSION CRITERIA - I -
• 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.
ORAL HEROIN CLINICAL TRIAL
INCLUSION CRITERIA - II • 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.
ORAL HEROIN CLINICAL TRIAL
INCLUSION CRITERIA - III • 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.
ORAL HEROIN CLINICAL TRIAL
EXCLUSION CRITERIA - I • 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.
ORAL HEROIN CLINICAL TRIAL
EXCLUSION CRITERIA - II • 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.
ORAL HEROIN CLINICAL TRIAL
EXCLUSION CRITERIA - III • 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
ORAL HEROIN CLINICAL TRIAL
EXCLUSION CRITERIA - IV • 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.
Direcció General de Drogodependències i SIDA
Generalitat de Catalunya
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 Barcelona
Hospital de la Santa Creu i Sant Pau
Hospital Mútua de Terrassa