A Four-Month Gatifloxacin-Containing Regimen for Treating Tuberculosis

作者：Corinne Simone Merle, Katherine Fielding, Omou Bah Sow, Martin Gninafon, Mame Bocar Lo, Thuli Mthiyane, Joseph A. Odhiambo, Evans Amukoye, Boubacar Bah, Ferdinand Kassa, Alimatou N′Diaye, Roxana Rustomjee, Bouke Catherine de Jong, John D. Horton, Christian Perronne, Charalambos Sismanidis, Olivier Lapujade, Piero Olliaro, Christian Lienhardt · 发表于：New England Journal of Medicine · 年份：2014 · DOI：10.1056/nejmoa1315817 · 被引用次数：410 · 研究领域：Tuberculosis Research and Epidemiology、Malaria Research and Control、Pneumonia and Respiratory Infections

BACKGROUND: Shortening the course of treatment for tuberculosis would be a major improvement for case management and disease control. This phase 3 trial assessed the efficacy and safety of a 4-month gatifloxacin-containing regimen for treating rifampin-sensitive pulmonary tuberculosis. METHODS: We conducted a noninferiority, randomized, open-label, controlled trial involving patients 18 to 65 years of age with smear-positive, rifampin-sensitive, newly diagnosed pulmonary tuberculosis in five sub-Saharan African countries. A standard 6-month regimen that included ethambutol during the 2-month intensive phase was compared with a 4-month regimen in which gatifloxacin (400 mg per day) was substituted for ethambutol during the intensive phase and was continued, along with rifampin and isoniazid, during the continuation phase. The primary efficacy end point was an unfavorable outcome (treatment failure, recurrence, or death or study dropout during treatment) measured 24 months after the end of treatment, with a noninferiority margin of 6 percentage points, adjusted for country. RESULTS: A total of 1836 patients were assigned to the 4-month regimen (experimental group) or the standard regimen (control group). Baseline characteristics were well balanced between the groups. At 24 months after the end of treatment, the adjusted difference in the risk of an unfavorable outcome (experimental group [21.0%] minus control group [17.2%]) in the modified intention-to-treat population (1356 pa...