Jindani A, Nunn A J, Enarson D A
International Union Against Tuberculosis and Lung Disease, 68 Boulevard Saint-Michel, 75006 Paris, France.
Lancet. 2004;364(9441):1244-51. doi: 10.1016/S0140-6736(04)17141-9.
A WHO-recommended 8-month regimen based on ethambutol and isoniazid was evaluated in a randomised clinical trial against a 6-month standard regimen.
1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were randomly assigned one of three regimens: daily ethambutol, isoniazid, rifampicin, and pyrazinamide for 2 months, followed by ethambutol and isoniazid for 6 months (2EHRZ/6HE); the same drugs but given three times weekly in the initial intensive phase (2[EHRZ]3/6HE); or the same initial intensive phase as the first regimen, followed by 4 months of daily rifampicin and isoniazid (2EHRZ/4HR). Follow-up was to 30 months after the start of chemotherapy. Sputum was regularly examined by microscopy and culture. Unfavourable outcome was defined as failure during treatment or relapse afterwards. Analyses were by intention to treat.
At 2 months, a significantly higher proportion of patients assigned the daily intensive phase than of those assigned the three-times-weekly regimen were culture negative (700/828 [85%] vs 333/433 [77%], p=0.001). 12 months after the end of chemotherapy, the proportions of unfavourable outcomes were 36 of 346 (10%) with 2EHRZ/6HE, 48 of 351 (14%) with 2(EHRZ)3/6HE, and 17 of 347 (5%) with 2EHRZ/4HR. Both 8-month regimens were significantly inferior to the control 6-month standard regimen (difference between control and 2EHRZ/6HE 5.5% [95% CI 1.6 to 9.4]; between control and 2(EHRZ)3/6HE 8.8% [4.5 to 13.0]). Adverse effects leading to interruption of treatment for 7 days or longer occurred in 28 patients (12 2EHRZ/6HE, five 2[EHRZ]3/6HE, 11 2EHRZ/4HR).
The results of this study must be taken into account in recommendations on management of new cases of smear-positive tuberculosis.
在一项随机临床试验中，对一种基于乙胺丁醇和异烟肼的世卫组织推荐的8个月疗程与6个月标准疗程进行了评估。
1355例新诊断的涂片阳性肺结核患者被随机分配到三种疗程之一：每日服用乙胺丁醇、异烟肼、利福平及吡嗪酰胺2个月，随后服用乙胺丁醇和异烟肼6个月（2EHRZ/6HE）；相同药物，但在初始强化期每周服用三次（2[EHRZ]3/6HE）；或与第一个疗程相同的初始强化期，随后每日服用利福平和异烟肼4个月（2EHRZ/4HR）。化疗开始后随访至30个月。定期通过显微镜检查和培养来检查痰液。不良结局定义为治疗期间失败或之后复发。分析采用意向性治疗。
在2个月时，分配到每日强化期的患者中培养转阴的比例显著高于分配到每周三次疗程的患者（700/828 [85%] 对333/433 [77%]，p=0.001）。化疗结束12个月后，2EHRZ/6HE组346例中有36例（10%）出现不良结局，2(EHRZ)3/6HE组351例中有48例（14%），2EHRZ/4HR组347例中有17例（5%）。两种8个月疗程均显著劣于对照6个月标准疗程（对照组与2EHRZ/6HE组的差异为5.5% [95%CI 1.6至9.4]；对照组与2(EHRZ)3/6HE组的差异为8.8% [4.5至13.0]）。导致治疗中断7天或更长时间的不良反应发生在28例患者中（2EHRZ/6HE组12例，2[EHRZ]3/6HE组5例，2EHRZ/4HR组11例）。
在关于涂片阳性结核病新病例管理的建议中必须考虑本研究结果。
