TY - JOUR
T1 - Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM)
T2 - Study protocol for a randomized controlled trial
AU - Nunn, Andrew J.
AU - Rusen, I. D.
AU - Van Deun, Armand
AU - Torrea, Gabriela
AU - Phillips, Patrick P.J.
AU - Chiang, Chen Yuan
AU - Squire, S. Bertel
AU - Madan, Jason
AU - Meredith, Sarah K.
N1 - Publisher Copyright:
© 2014 Nunn et al.; licensee BioMed Central Ltd.
PY - 2014/9/9
Y1 - 2014/9/9
N2 - 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/Design: 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.Discussion: 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.Trial registration: This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.
AB - 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/Design: 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.Discussion: 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.Trial registration: This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.
KW - Multi-drug-resistant tuberculosis
KW - Multicenter randomized trial
KW - Non-inferiority
KW - Shorter treatment duration
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U2 - 10.1186/1745-6215-15-353
DO - 10.1186/1745-6215-15-353
M3 - Article
C2 - 25199531
AN - SCOPUS:84907022895
SN - 1745-6215
VL - 15
JO - Trials
JF - Trials
IS - 1
M1 - 353
ER -
