Two 8-month regimens of chemotherapy for treatment of newly diagnosed pulmonary tuberculosis: international multicentre randomised trial
Two 8-month regimens of chemotherapy for treatment of newly diagnosed pulmonary tuberculosis: international multicentre randomised trial
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DOI：
10.1016/s0140-6736(04)17141-9
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发表时间：
2004-10-02
期刊：
影响因子：
168.9
通讯作者：
Enarson, DA
中科院分区：
文献类型：
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作者：
Jindani, A;Nunn, AJ;Enarson, DA
方法1355例初治涂阳肺结核患者随机分为3种方案：每日服用乙胺丁醇、异烟肼、利福平、吡嗪酰胺，疗程2个月，随后每日服用乙胺丁醇、异烟肼，疗程6个月(2EHRZ/6HE)；相同药物，在初始强化阶段每周给予3次(2[EHRZ](3)/6HE)；或与第一种方案相同的初始强化阶段，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。常规进行痰标本镜检和培养。不良结局定义为治疗失败或治疗后复发。根据治疗意向进行分析。2个月后发现，被分配每日强化阶段的患者比那些被分配每周三次方案的患者培养阴性的比例明显更高(700vs333[77%]，p=0.001)。化疗结束12个月后，2EHRZ/6HE组不良预后36例(10%)，2(EHRZ)(3)/6HE组48例(14%)，2EHRZ/4HR组17例(5%)。两组8个月方案均明显低于对照组6个月标准方案(对照组与2EHRZ/6HE5.5%[95%CI 1.6~9.4]；对照组与2(EHRZ)(3)/6HE 8.8%[4.5~13.01])。28例患者出现了导致治疗中断7天或更长时间的不良反应(12例EHRZ/6HE，5例2[EHRZ](3)/6HE，11 2EHRZ/4HR)。
Background A WHO-recommended 8-month regimen based on ethambutol and isoniazid was evaluated in a randomised clinical trial against a 6-month standard regimen.Methods 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.Findings 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 13.01]). 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).Interpretation The results of this study must be taken into account in recommendations on management of new cases of smear-positive tuberculosis.