Jindani Amina, Harrison Thomas S, Nunn Andrew J, Phillips Patrick P J, Churchyard Gavin J, Charalambous Salome, Hatherill Mark, Geldenhuys Hennie, McIlleron Helen M, Zvada Simbarashe P, Mungofa Stanley, Shah Nasir A, Zizhou Simukai, Magweta Lloyd, Shepherd James, Nyirenda Sambayawo, van Dijk Janneke H, Clouting Heather E, Coleman David, Bateson Anna L E, McHugh Timothy D, Butcher Philip D, Mitchison Denny A
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.).
N Engl J Med. 2014 Oct 23;371(17):1599-608. doi: 10.1056/NEJMoa1314210.
Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed.
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.
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).
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.).
需要比目前的6个月每日用药方案更短、更简单的结核病治疗方案。
我们将新诊断的、涂片阳性、药物敏感的结核病患者随机分为三种治疗方案之一：对照方案，包括每日服用乙胺丁醇、异烟肼、利福平和平吡嗪酰胺2个月，随后每日服用异烟肼和利福平4个月；4个月方案，其中对照方案中的异烟肼被莫西沙星替代，每日服用2个月，随后莫西沙星和900毫克利福喷汀每周服用两次，共2个月；或6个月方案，其中异烟肼被莫西沙星每日替代2个月，随后莫西沙星和1200毫克利福喷汀每周服用一次，共4个月。定期对痰标本进行显微镜检查和培养检查。主要终点是综合治疗失败和复发，非劣效性基于6个百分点的差值和90%置信区间。
我们共纳入了来自南非、津巴布韦、博茨瓦纳和赞比亚的827名患者；28%的患者同时感染了人类免疫缺陷病毒。在符合方案分析中，对照组中治疗反应不佳的患者比例为4.9%，6个月组为3.2%（与对照组的调整差值为-1.8个百分点；90%置信区间[CI]，-6.1至2.4），4个月组为18.2%（与对照组的调整差值为13.6个百分点；90%CI，8.1至19.1）。在改良意向性分析中，这些比例在对照组中为14.4%，6个月组为13.7%（与对照组的调整差值为0.4个百分点；90%CI，-4.7至5.6），4个月组为26.9%（与对照组的调整差值为13.1个百分点；90%CI，6.8至19.4）。
包括每周服用高剂量利福喷汀和莫西沙星的6个月方案与对照方案效果相同。4个月方案不劣于对照方案。（由欧洲和发展中国家临床试验合作组织以及惠康信托基金资助；RIFAQUIN当前对照试验编号，ISRCTN44153044。）
