From the Center for Global Health and Diseases, Case Western Reserve University School of Medicine (C.L.K., Y.-C.C., B.M., J.W.K.), and the Veterans Affairs Medical Center (C.L.K.), Cleveland; Papua New Guinea Institute of Medical Research, Goroka (J.S., N.S., S.S., L.J.R., P.M.S.); and the Division of Biostatistics (C.W.G.) and Department of Medicine, Infectious Diseases Division (G.J.W.), Washington University School of Medicine, St. Louis.
N Engl J Med. 2018 Nov 8;379(19):1801-1810. doi: 10.1056/NEJMoa1706854.
The World Health Organization has targeted lymphatic filariasis for global elimination by 2020 with a strategy of mass drug administration. This trial tested whether a single dose of a three-drug regimen of ivermectin plus diethylcarbamazine plus albendazole results in a greater sustained clearance of microfilariae than a single dose of a two-drug regimen of diethylcarbamazine plus albendazole and is noninferior to the two-drug regimen administered once a year for 3 years.
In a randomized, controlled trial involving adults from Papua New Guinea with Wuchereria bancrofti microfilaremia, we assigned 182 participants to receive a single dose of the three-drug regimen (60 participants), a single dose of the two-drug regimen (61 participants), or the two-drug regimen once a year for 3 years (61 participants). Clearance of microfilariae from the blood was measured at 12, 24, and 36 months after trial initiation.
The three-drug regimen cleared microfilaremia in 55 of 57 participants (96%) at 12 months, in 52 of 54 participants (96%) at 24 months, and in 55 of 57 participants (96%) at 36 months. A single dose of the two-drug regimen cleared microfilaremia in 18 of 56 participants (32%) at 12 months, in 31 of 55 participants (56%) at 24 months, and in 43 of 52 participants (83%) at 36 months (P=0.02 for the three-drug regimen vs. a single dose of the two-drug regimen at 36 months). The two-drug regimen administered once a year for 3 years cleared microfilaremia in 20 of 59 participants (34%) at 12 months, in 42 of 56 participants (75%) at 24 months, and in 51 of 52 participants (98%) at 36 months (P=0.004 for noninferiority of the three-drug regimen vs. the two-drug regimen administered once a year for 3 years at 36 months). Moderate adverse events were more common in the group that received the three-drug regimen than in the combined two-drug-regimen groups (27% vs. 5%, P<0.001). There were no serious adverse events.
The three-drug regimen induced clearance of microfilariae from the blood for 3 years in almost all participants who received the treatment and was superior to the two-drug regimen administered once and noninferior to the two-drug regimen administered once a year for 3 years. (Funded by the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT01975441 .).
世界卫生组织（WHO）已将淋巴丝虫病作为全球消除的目标，计划在 2020 年前采用大剂量药物治疗的策略。本试验旨在测试伊维菌素、乙胺嗪和阿苯达唑三联疗法单剂量治疗是否比乙胺嗪和阿苯达唑二联疗法单剂量治疗更能持续清除微丝蚴，以及其是否与 3 年中每年一次的二联疗法非劣效。
在一项涉及巴布亚新几内亚成年班氏丝虫病微丝蚴血症患者的随机对照试验中，我们将 182 名参与者分为三组，分别接受三联疗法单剂量（60 名参与者）、二联疗法单剂量（61 名参与者）或二联疗法每年一次治疗 3 年（61 名参与者）。在试验开始后 12、24 和 36 个月时测量血液中微丝蚴的清除情况。
三联疗法在 12 个月时清除了 57 名参与者中的 55 名（96%）的微丝蚴血症，在 24 个月时清除了 54 名参与者中的 52 名（96%），在 36 个月时清除了 57 名参与者中的 55 名（96%）。二联疗法单剂量在 12 个月时清除了 56 名参与者中的 18 名（32%），在 24 个月时清除了 55 名参与者中的 31 名（56%），在 36 个月时清除了 52 名参与者中的 43 名（83%）（与 36 个月时二联疗法相比，P=0.02）。每年一次的三联疗法治疗 3 年，在 12 个月时清除了 59 名参与者中的 20 名（34%），在 24 个月时清除了 56 名参与者中的 42 名（75%），在 36 个月时清除了 52 名参与者中的 51 名（98%）（与 3 年的二联疗法相比，P=0.004）。非劣效性。三联疗法治疗组的中度不良事件比联合二联疗法治疗组更常见（27%比 5%，P<0.001）。没有严重的不良事件。
三联疗法在几乎所有接受治疗的参与者中诱导血液中微丝蚴清除 3 年，优于二联疗法单剂量治疗，与每年一次的二联疗法 3 年治疗非劣效。（由比尔和梅林达盖茨基金会资助；临床试验.gov 编号，NCT01975441）。
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