TABAQUISMO EN PACIENTES PSIQUIATRICOS

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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
Direcció General de Drogodependències i
SIDA Generalitat de Catalunya

• Hospital Universitari Vall d Hebron de
  Barcelona
• Hospital de la Santa Creu i Sant Pau
• Hospital Mútua de Terrassa

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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.

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Effectiveness of oral heroin
ORAL HEROIN CLINICAL TRIAL

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

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

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ORAL HEROIN CLINICAL TRIAL
DESIGN

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

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ORAL HEROIN CLINICAL TRIAL

• Clinical Trial Phase III
• Design Controlled, double blind, in
  parallel, of 4 randomly assigned
  experimental groups .
• Flexible dose

Patient
Physician
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Length 6 months
ORAL HEROIN CLINICAL TRIAL
DESIGN

• Induction phase 14 days hospitilization.
• Maintenance phase 166 days of outpatient
• with 2 daily doses.

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ORAL HEROIN CLINICAL TRIAL
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

X 3
X 3
X 3
X 3
X 3
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ORAL HEROIN CLINICAL TRIAL
MAIN VARIABLES

• 1.- Subject treatment retention in the
  study.
• 2.- Consumption of non - prescribed opioids.

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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.

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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.

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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
  psycho-pathology between the four groups.

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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.

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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.

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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.

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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.

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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.

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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.

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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

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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.

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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
Direcció General de Drogodependències i
SIDA Generalitat de Catalunya

• Hospital Universitari Vall d Hebron de
  Barcelona
• Hospital de la Santa Creu i Sant Pau
• Hospital Mútua de Terrassa