SWOG Statistical Center, Cancer Research and Biostatistics, Seattle, WA 98101-1468, USA.
Lancet. 2011 Aug 6;378(9790):507-14. doi: 10.1016/S0140-6736(11)60825-8. Epub 2011 Jul 21.
Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy.
Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21-65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6-8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, registration number NCT01061437.
1463 participants aged 21-65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6-14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (-0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites.
Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations.
Bill & Melinda Gates Foundation, US National Institutes of Health.
来自欧洲、亚洲和北美的证据表明，质子泵抑制剂加阿莫西林和克拉霉素的标准三联药物方案对于根除幽门螺杆菌感染的效果明显不如包括硝基咪唑在内的 5 天同时和 10 天序贯的四联药物方案。这四种药物方案也比三联药物方案需要更少的抗生素剂量，因此可能适合资源有限环境中的根除方案。在拉丁美洲进行的研究很少，而那里的幽门螺杆菌相关疾病负担很高。因此，我们在拉丁美洲进行了一项随机试验，比较了同时或序贯给予四联药物方案与标准的 14 天三联药物治疗方案的效果。
在 2009 年 9 月至 2010 年 6 月期间，我们在七个拉丁美洲地点（智利、哥伦比亚、哥斯达黎加、洪都拉斯、尼加拉瓜和墨西哥（两个地点））进行了一项随机试验，对经验性的 14 天三联药物、5 天同时和 10 天序贯治疗幽门螺杆菌的效果进行了随机试验。年龄在 21-65 岁之间的参与者通过尿素呼气试验检测出幽门螺杆菌阳性，通过中央计算机使用动态平衡程序随机分配到以下三组：14 天的兰索拉唑、阿莫西林和克拉霉素（标准治疗）；5 天的兰索拉唑、阿莫西林、克拉霉素和甲硝唑（同时治疗）；或 5 天的兰索拉唑和阿莫西林，随后 5 天的兰索拉唑、克拉霉素和甲硝唑（序贯治疗）。随机分组后 6-8 周通过尿素呼气试验评估根除情况。试验未设盲。我们的主要结局是幽门螺杆菌根除的可能性。我们的分析是基于意向治疗。该试验在 ClinicalTrials.gov 上注册，注册号为 NCT01061437。
共有 1463 名年龄在 21-65 岁之间的参与者被随机分配到治疗组：488 名接受 14 天标准治疗，489 名接受 5 天同时治疗，486 名接受 10 天序贯治疗。标准治疗的根除率为 82.2%（401/488），比同时治疗（73.6%[360/489]）高 8.6%（调整后的 95%置信区间 2.6-14.5），比序贯治疗（76.5%[372/486]）高 5.6%（-0.04%至 11.6）。在这七个地点中的任何一个地点，四联药物方案都没有明显优于标准三联药物治疗。
标准的 14 天三联药物治疗是优于 5 天同时或 10 天序贯四联药物方案，作为经验性治疗在拉丁美洲不同人群的幽门螺杆菌感染。
比尔及梅琳达·盖茨基金会，美国国立卫生研究院。
