Department of Clinical Sciences, Tropical Diseases Research Centre, P.O. Box 71769, Copperbelt Province, Ndola, Zambia.
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Trials. 2021 Nov 20;22(1):820. doi: 10.1186/s13063-021-05745-0.
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization for the prevention of malaria in pregnancy (MIP)-associated adverse outcomes in high burden areas. However, the efficacy of IPTp-SP has decreased in step with increasing parasite drug resistance. Suitable alternative strategies are needed.
This is a protocol for a phase IIIb open-label, two-armed randomized controlled superiority trial to assess the safety and efficacy of a hybrid approach to IPTp combining screening and treatment with dihydroartemisinin-piperaquine (DP) to the current IPTp-SP regimen at the first antenatal care clinic visit. Pregnant women without HIV infection and without signs or symptoms of malaria will be randomized to either standard IPTp-SP or hybrid IPTp-SP plus screening and treatment (IPTp-SP+). In the IPTp-SP+ arm, participants who screen positive by rapid diagnostic test for P. falciparum will be treated with DP at the first antenatal visit while those who screen negative will receive SP per current guidelines. All participants will be administered SP on days 35 and 63 and will be actively followed biweekly up to day 63 and then monthly until delivery. Infants will be followed until 1 year after delivery. The primary endpoint is incident PCR-confirmed MIP at day 42. Secondary endpoints include incident MIP at other time points, placental malaria, congenital malaria, hemoglobin trends, birth outcomes, and incidence of adverse events in infants up to the first birthday.
A hybrid approach to IPTp that combines screening and treatment with an artemisinin-based combination therapy at the first visit with standard IPTp-SP is hypothesized to confer added benefit over IPTp-SP alone in a high malaria transmission area with prevalent SP resistant parasites.
Pan African Clinical Trials Registry 201905721140808 . Registered retrospectively on 11 May 2019.
世界卫生组织建议在高负担地区采用磺胺多辛-乙胺嘧啶（SP）间歇性预防治疗（IPTp）来预防妊娠疟疾（MIP）相关不良结局。然而，随着寄生虫对药物的耐药性增加，IPTp-SP 的疗效已经下降。需要寻找合适的替代策略。
这是一项 IIIb 期开放标签、双臂随机对照优效性试验的方案，旨在评估在第一次产前保健诊所就诊时，采用二氢青蒿素-哌喹（DP）筛查和治疗与现行 IPTp-SP 方案相结合的混合方法来预防 MIP 的安全性和疗效。无 HIV 感染且无疟疾体征或症状的孕妇将随机分为标准 IPTp-SP 组或混合 IPTp-SP+组。在 IPTp-SP+组中，通过快速诊断检测对恶性疟原虫呈阳性的参与者将在第一次产前就诊时接受 DP 治疗，而呈阴性的参与者将按照现行指南接受 SP 治疗。所有参与者将在第 35 天和第 63 天接受 SP 治疗，并在第 63 天之前每两周进行主动随访，然后每月随访直至分娩。婴儿将随访至分娩后 1 年。主要终点是第 42 天 PCR 确诊的 MIP 发生率。次要终点包括其他时间点的 MIP 发生率、胎盘疟疾、先天性疟疾、血红蛋白趋势、分娩结局以及婴儿至 1 岁生日时的不良事件发生率。
在高疟疾传播地区，采用在第一次就诊时用基于青蒿素的联合疗法进行筛查和治疗的混合方法来预防 MIP，与单独使用 IPTp-SP 相比，预计会带来额外的益处。在该地区，SP 耐药寄生虫普遍存在。
泛非临床试验注册中心 201905721140808。于 2019 年 5 月 11 日回顾性注册。
