title: Feasibility of double-blind clinical trials with oral diacetylmorphine: a randomized controlled phase II study in an inpatient setting.
abstract: The aim of this study was to evaluate the feasibility of conducting double-blind controlled randomized clinical trials using twice-a-day immediate-release oral diacetylmorphine (DAM) in heroin-dependent patients, by means of measuring the capacity of oral DAM to block opiate withdrawal and clinicians' ability to distinguish it from morphine and methadone. This was a randomized, phase II, double-blind, multicenter pilot study comparing immediate-release oral DAM, slow-release oral morphine and oral methadone administered twice a day during 10 days. Forty-five heroin-dependent patients were randomly assigned to these three treatment groups in an inpatient regime. Patients were stabilized with a mean of 350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow-release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically significant differences were found between any studied medication in clinical outcome. Neither patients nor clinicians were able to identify the administered medication. This study shows the feasibility of double-blind clinical trials using b.i.d. immediate-release oral DAM allowing further phase III clinical trials in the process of introducing oral DAM as a medication for heroin-dependent patients not responding to standard maintenance treatments.
authors.affiliation: Programme on Substance Abuse, Public Health Agency of Catalonia, Government of Catalonia, Barcelona, Spain. joan.colom@gencat.cat
authors.forename: Joan
authors.initials: J
authors.lastname: Colom Farran
authors.forename: Miguel
authors.initials: M
authors.lastname: Casas
authors.forename: José
authors.initials: J
authors.lastname: Pérez de Los Cobos
authors.forename: Miquel
authors.initials: M
authors.lastname: Del Río
authors.forename: Carlos
authors.initials: C
authors.lastname: Roncero
authors.forename: Xavier
authors.initials: X
authors.lastname: Castells
authors.forename: Sergi
authors.initials: S
authors.lastname: Valero
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Eiroa-Orosa
authors.forename: Francisca
authors.initials: F
authors.lastname: Batlle
authors.forename: Joan
authors.initials: J
authors.lastname: Trujols
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016739:Behavior, Addictive / Q000188:drug therapy / Q000523:psychology; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D003932:Heroin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006556:Heroin Dependence / Q000188:drug therapy*; D006801:Humans; D007297:Inpatients / Q000523:psychology; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment / Q000379:methods / Q000523:psychology*; D010820:Physicians / Q000523:psychology; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data
chemical_list: D003692:Delayed-Action Preparations; D003932:Heroin; D009020:Morphine; D008691:Methadone