title: Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant tuberculosis (MDR-TB) have a very poor evidence base; current recommendations, based on expert opinion, are that patients should be treated for a minimum of 20 months. A series of cohort studies conducted in Bangladesh identified a nine-month regimen with very promising results. There is a need to evaluate this regimen in comparison with the currently recommended regimen in a randomized controlled trial in a variety of settings, including patients with HIV-coinfection.
  
  
  METHODS
  STREAM is a multi-centre randomized trial of non-inferiority design comparing a nine-month regimen to the treatment currently recommended by the World Health Organization in patients with MDR pulmonary TB with no evidence on line probe assay of fluoroquinolone or kanamycin resistance. The nine-month regimen includes clofazimine and high-dose moxifloxacin and can be extended to 11 months in the event of delay in smear conversion. The primary outcome is based on the bacteriological status of the patients at 27 months post-randomization. Based on the assumption that the nine-month regimen will be slightly more effective than the control regimen and, given a 10% margin of non-inferiority, a total of 400 patients are required to be enrolled. Health economics data are being collected on all patients in selected sites.
  
  
  CONCLUSIONS
  The results from the study in Bangladesh and cohorts in progress elsewhere are encouraging, but for this regimen to be recommended more widely than in a research setting, robust evidence is needed from a randomized clinical trial. Results from the STREAM trial together with data from ongoing cohorts should provide the evidence necessary to revise current recommendations for the treatment for MDR-TB.
  
  
  BACKGROUND
  This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.
authors.affiliation: Medical Research Council Clinical Trials Unit at University College London, Institute of Clinical Trials & Methodology, Aviation House, 125 Kingsway, London WC2B 6NH, UK. andrew.nunn@ucl.ac.uk.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Nunn
authors.forename: I D
authors.initials: ID
authors.lastname: Rusen
authors.forename: Armand
authors.initials: A
authors.lastname: Van Deun
authors.forename: Gabriela
authors.initials: G
authors.lastname: Torrea
authors.forename: Patrick P J
authors.initials: PP
authors.lastname: Phillips
authors.forename: Chen-Yuan
authors.initials: CY
authors.lastname: Chiang
authors.forename: S Bertel
authors.initials: SB
authors.lastname: Squire
authors.forename: Jason
authors.initials: J
authors.lastname: Madan
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Meredith
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage*; D001459:Bangladesh; D002985:Clinical Protocols; D002991:Clofazimine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage; D024841:Fluoroquinolones / Q000008:administration & dosage; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage; D007612:Kanamycin / Q000008:administration & dosage; D000077266:Moxifloxacin; D011515:Prothionamide / Q000008:administration & dosage; D011718:Pyrazinamide / Q000008:administration & dosage; D012107:Research Design; D013997:Time Factors; 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: D000995:Antitubercular Agents; D024841:Fluoroquinolones; D011718:Pyrazinamide; D007612:Kanamycin; D011515:Prothionamide; D004977:Ethambutol; D002991:Clofazimine; D000077266:Moxifloxacin; D007538:Isoniazid