title: Rationale and design of a randomized controlled trial of directly observed hepatitis C treatment delivered in methadone clinics.
abstract: BACKGROUND
  Most methadone-maintained injection drug users (IDUs) have been infected with hepatitis C virus (HCV), but few initiate HCV treatment. Physicians may be reluctant to treat HCV in IDUs because of concerns about treatment adherence, psychiatric comorbidity, or ongoing drug use. Optimal HCV management approaches for IDUs remain unknown. We are conducting a randomized controlled trial in a network of nine methadone clinics with onsite HCV care to determine whether modified directly observed therapy (mDOT), compared to treatment as usual (TAU), improves adherence and virologic outcomes among opioid users.
  
  
  METHODS
  We plan to enroll 80 HCV-infected adults initiating care with pegylated interferon alfa-2a (IFN) plus ribavirin, and randomize them to mDOT (directly observed daily ribavirin plus provider-administered weekly IFN) or TAU (self-administered ribavirin plus provider-administered weekly IFN). Our outcome measures are: 1) self-reported and pill count adherence, and 2) end of treatment response (ETR) or sustained viral response (SVR). We will use mixed effects linear models to assess differences in pill count adherence between treatment arms (mDOT v. TAU), and we will assess differences between treatment arms in the proportion of subjects with ETR or SVR with chi square tests. Of the first 40 subjects enrolled: 21 have been randomized to mDOT and 19 to TAU. To date, the sample is 77% Latino, 60% HCV genotype-1, 38% active drug users, and 27% HIV-infected. Our overall retention rate at 24 weeks is 92%, 93% in the mDOT arm and 92% in the TAU arm.
  
  
  CONCLUSIONS
  This paper describes the design and rationale of a randomized clinical trial comparing modified directly observed HCV therapy delivered in a methadone program to on-site treatment as usual. Our trial will allow rigorous evaluation of the efficacy of directly observed HCV therapy (both pegylated interferon and ribavirin) for improving adherence and clinical outcomes. This detailed description of trial methodology can serve as a template for the development of future DOT programs, and can also guide protocols for studies among HCV-infected drug users receiving methadone for opiate dependence.
authors.affiliation: Division of General Internal Medicine, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10467, USA. alitwin@montefiore.org
authors.forename: Alain H
authors.initials: AH
authors.lastname: Litwin
authors.forename: Karina M
authors.initials: KM
authors.lastname: Berg
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hidalgo
authors.forename: Julia H
authors.initials: JH
authors.lastname: Arnsten
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage; D023801:Directly Observed Therapy / Q000379:methods; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D012107:Research Design; D012254:Ribavirin / Q000008:administration & dosage; D019966:Substance-Related Disorders / Q000150:complications* / Q000188:drug therapy*; D016896:Treatment Outcome; D016903:Drug Monitoring
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a; D008691:Methadone
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