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N Engl J Med. 2014 Oct 23;371(17):1599-608. doi: 10.1056/NEJMoa1314210.

High-dose rifapentine with moxifloxacin for pulmonary tuberculosis.

Author information

1
From St. George's, University of London (A.J., D.A.M., T.S.H., D.C., P.D.B.), Medical Research Council Clinical Trials Unit at University College London (A.J.N., P.P.J.P., H.E.C.), and University College London Centre for Clinical Biology, University College London (A.L.E.B., T.D.M.), London; Aurum Institute (G.J.C., S.C.) and School of Public Health, University of the Witwatersrand (G.J.C.), Johannesburg, and South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and School of Child and Adolescent Health (M.H., H.G.) and Division of Clinical Pharmacology, Department of Medicine (H.M.M., S.P.Z.), University of Cape Town, Cape Town - all in South Africa; Harare City Health Department, Harare (S.M., N.A.S.S.), and Medical Directorate of Mashonaland East, Marondera (S.Z., L.M.) - both in Zimbabwe; CDC, Gaborone, Botswana (J.S., S.N.); and Macha Research Trust, Macha, Zambia (J.H.D.).

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.).

PMID:
25337749
PMCID:
PMC4233406
DOI:
10.1056/NEJMoa1314210
[Indexed for MEDLINE]
Free PMC Article

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