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ABSTRACT: Background
Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed.Methods
We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals.Results
We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, -1.8 percentage points; 90% confidence interval [CI], -6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, -4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4).Conclusions
The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.).
SUBMITTER: Jindani A
PROVIDER: S-EPMC4233406 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Jindani Amina A Harrison Thomas S TS Nunn Andrew J AJ Phillips Patrick P J PP Churchyard Gavin J GJ Charalambous Salome S Hatherill Mark M Geldenhuys Hennie H McIlleron Helen M HM Zvada Simbarashe P SP Mungofa Stanley S Shah Nasir A NA Zizhou Simukai S Magweta Lloyd L Shepherd James J Nyirenda Sambayawo S van Dijk Janneke H JH Clouting Heather E HE Coleman David D Bateson Anna L E AL McHugh Timothy D TD Butcher Philip D PD Mitchison Denny A DA
The New England journal of medicine 20141001 17
<h4>Background</h4>Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed.<h4>Methods</h4>We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was rep ...[more]