title: Lessons from a randomised clinical trial for multidrug-resistant tuberculosis.
abstract: BACKGROUND
  The treatment of multidrug-resistant tuberculosis (MDR-TB) is currently based upon expert opinion and findings from case series, rather than upon randomised clinical trials (RCTs).
  
  
  OBJECTIVE
  To describe the challenges encountered during an RCT for the treatment of MDR-TB.
  
  
  METHODS
  Tuberculosis Trials Consortium Study 30 was a pilot, Phase I/II, double-blind, placebo-controlled, RCT of the safety and tolerability of 16 weeks of daily, low-dose linezolid treatment for MDR-TB.
  
  
  RESULTS
  A total of 36 patients, 56% of the target of 64 patients, consented to participate,  for an average of 0.69 enrolments per week. Of the 36 patients enrolled, only 25 (69%) completed at least 90 doses of study treatment. Among the 12 (33%) patients who did not complete all 112 doses of the study treatment, the median time to study withdrawal was 15 days (range 0-92).  After the study, we discovered discordance between treatment assignment and study drug for at least 9 (25%) of the 36 patients.
  
  
  CONCLUSIONS
  Recruitment and retention in this MDR-TB clinical trial posed substantial challenges, suggesting the need for a large, multidisciplinary group of  study staff to support the participants. Withdrawal tended to occur early in study treatment. The discrepancy in assigned study medication reflects the need for stronger administrative controls for study drugs.
authors.affiliation: Centre for AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: N
authors.initials: N
authors.lastname: Padayatchi
authors.forename: W R
authors.initials: WR
authors.lastname: Mac Kenzie
authors.forename: Y
authors.initials: Y
authors.lastname: Hirsch-Moverman
authors.forename: P-J
authors.initials: PJ
authors.lastname: Feng
authors.forename: E
authors.initials: E
authors.lastname: Villarino
authors.forename: J
authors.initials: J
authors.lastname: Saukkonen
authors.forename: C M
authors.initials: CM
authors.lastname: Heilig
authors.forename: M
authors.initials: M
authors.lastname: Weiner
authors.forename: W M
authors.initials: WM
authors.lastname: El-Sadr
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D023801:Directly Observed Therapy; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D010352:Patient Dropouts; D010865:Pilot Projects; D012107:Research Design; D013019:South Africa; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D000069349:Linezolid