who_casas by xiaohuicaicai

VIEWS: 0 PAGES: 22

									    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    diverse
  means of heroin administration :

               •   Intravenous
               •   Smoked
               •   Inhaled
               •   Oral
               •   Suppositories
               •   Transcutaneous
 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.
ORAL HEROIN CLINICAL TRIAL
   • Clinical Trial Phase III


   • Design:    Controlled, double blind,
                in parallel, of 4 randomly
                assigned experimental
                groups .

                      Patient
   • Flexible dose
                      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        n = 60   X3

         • Diacetylmorphine   n = 15   X3
         • Morphine           n = 15   X3
         • Metadone I         n = 15   X3
         • Metadone II        n = 15   X3
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 psycho-
  pathology 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

								
To top