Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria
Tafenoquine versus Primaquine to Prevent Relapse of Plasmodium vivax Malaria
复制标题
DOI：
10.1056/nejmoa1802537
复制
发表时间：
2019-01-17
影响因子：
158.5
通讯作者：
Green, J. A.
中科院分区：
文献类型：
--
作者：
Llanos-Cuentas, A.;Lacerda, M. V. G.;Green, J. A.
背景他非诺喹是治疗间日疟原虫疟疾的单剂量疗法，通过清除间日疟原虫血症和休眠子来预防复发，称为“根治”。方法我们进行了一项 3 期、前瞻性、双盲、双模拟、随机、对照试验，以比较他非诺喹与伯氨喹的安全性和有效性。该试验在秘鲁、巴西、哥伦比亚、越南和泰国的七家医院或诊所进行，涉及葡萄糖-6-磷酸脱氢酶（G6PD）酶活性正常的患者和中度 G6PD 酶缺乏的女性患者；所有患者均确诊有间日疟原虫寄生虫血症。患者按照 2:1 的比例被随机分配接受单次 300 mg 剂量的他非诺喹或 15 mg 伯氨喹，每日一次，持续 14 天（在监督下给药）；所有患者均接受为期 3 天的氯喹疗程，并随访 180 天。主要安全性结果是方案定义的血红蛋白水平下降（> 3.0 g/dL 或 = 较基线下降 30% 或降至 < 6.0 g/dL 水平）。在当前试验和他非诺喹和伯氨喹（符合方案人群）的另一项 3 期试验的计划患者级荟萃分析中，6 个月时无间日疟原虫血症复发是主要疗效结果，复发的比值比 1.45（他非诺喹与伯氨喹）被用作非劣效界。他非诺喹组 166 名患者中有 4 名（2.4%；95% CI，0.9 至 6.0），伯氨喹组 85 名患者中有 1 名（1.2%；95% CI，0.2 至 6.4），组间差异为 1.2 个百分点（95% CI，-4.2 至 5.0）。在患者层面的荟萃分析中，他非诺喹组的426名患者中6个月时未复发的患者比例为67.0%（95% CI，61.0至72.3），伯氨喹组的214名患者中为72.8%（95% CI，65.6至78.8）。他非诺喹的疗效并不逊色于伯氨喹（复发比值比，1.81；95% CI，0.82 至 3.96）。结论：在 G6PD 酶活性正常的患者中，他非诺喹治疗后血红蛋白水平的下降与伯氨喹治疗没有显着差异。他非诺喹对根治间日疟原虫疟疾显示出疗效，但他非诺喹并未显示出不劣于伯氨喹。
BACKGROUNDTafenoquine, a single-dose therapy for Plasmodium vivax malaria, has been associated with relapse prevention through the clearance of P. vivax parasitemia and hypnozoites, termed "radical cure."METHODSWe performed a phase 3, prospective, double-blind, double-dummy, randomized, controlled trial to compare tafenoquine with primaquine in terms of safety and efficacy. The trial was conducted at seven hospitals or clinics in Peru, Brazil, Colombia, Vietnam, and Thailand and involved patients with normal glucose-6-phosphate dehydrogenase (G6PD) enzyme activity and female patients with moderate G6PD enzyme deficiency; all patients had confirmed P. vivax parasitemia. The patients were randomly assigned, in a 2: 1 ratio, to receive a single 300-mg dose of tafenoquine or 15 mg of primaquine once daily for 14 days (administered under supervision); all patients received a 3-day course of chloroquine and were followed for 180 days. The primary safety outcome was a protocol-defined decrease in the hemoglobin level (> 3.0 g per deciliter or = 30% from baseline or to a level of < 6.0 g per deciliter). Freedom from recurrence of P. vivax parasitemia at 6 months was the primary efficacy outcome in a planned patient-level meta-analysis of the current trial and another phase 3 trial of tafenoquine and primaquine (per-protocol populations), and an odds ratio for recurrence of 1.45 (tafenoquine vs. primaquine) was used as a noninferiority margin.RESULTSA protocol-defined decrease in the hemoglobin level occurred in 4 of 166 patients (2.4%; 95% confidence interval [CI], 0.9 to 6.0) in the tafenoquine group and in 1 of 85 patients (1.2%; 95% CI, 0.2 to 6.4) in the primaquine group, for a between-group difference of 1.2 percentage points (95% CI, -4.2 to 5.0). In the patient-level meta-analysis, the percentage of patients who were free from recurrence at 6 months was 67.0% (95% CI, 61.0 to 72.3) among the 426 patients in the tafenoquine group and 72.8% (95% CI, 65.6 to 78.8) among the 214 patients in the primaquine group. The efficacy of tafenoquine was not shown to be noninferior to that of primaquine (odds ratio for recurrence, 1.81; 95% CI, 0.82 to 3.96).CONCLUSIONSAmong patients with normal G6PD enzyme activity, the decline in hemoglobin level with tafenoquine did not differ significantly from that with primaquine. Tafenoquine showed efficacy for the radical cure of P. vivax malaria, although tafenoquine was not shown to be noninferior to primaquine.