Comparison of Four IPTP Regimens for Efficacy and Safety in Pregnant Women

每年，疟疾传播区的数百万妇女怀孕，需要预防感染。由于具有抗药性的寄生虫，目前用于预防孕期疟疾的药物正在失效。该项目将评估用于妊娠疟疾间歇预防治疗(IPTp)的新方案的安全性、药代动力学和有效性，包括它们对后代的长期影响。在这里提出的研究中，三种新的方案(氯丙鸟-氨苯松(LapDap)、甲氟喹、磺胺多辛-乙胺嘧啶(SP)+ 将在疗效、药代动力学和安全性，包括对后代的长期影响方面，将阿奇霉素)与标准方案(仅SP)进行比较。这项拟议的项目基于以下假设：与标准IPTp相比，新的IPTp方案将显著增加新生儿体重和母亲血红蛋白；与SP相比，新的IPTp方案不会增加死产、流产或胎儿畸形的频率，也不会损害后代的神经发育结果；孕妇中抗疟疾药物的药代动力学将与以前在非孕妇中观察到的不同。这将是一项开放的随机对照试验，有四个IPTp臂。具体地说，这项研究将比较四种IPTp方案的临床(产妇贫血、出生体重)和寄生虫学反应(产妇寄生虫血症、胎盘寄生虫血症)和副作用。目标人群包括在莫罗戈罗地区医院接受常规产前护理的孕妇，ICDDR研究中心和培训计划将设在该医院。的主端点 试验的效果将是出生体重。短期毒性将通过仔细监测给药后的临床、血液学和生化异常以及寄生虫学反应来评估。IPTp的短期和中期安全性将通过产妇死亡率、围产期死亡率、产妇并发症和子代临床上明显的异常来评估。IPTp方案的长期安全性将在后代3年的随访中进行评估 标准化测试中听力异常或不良神经发育后果的证据。将使用以人群为基础的方法为每个方案定义药物药代动力学，以最大限度地减少血液采样。该项目的长期目标是确定更有效的IPTp方案来预防孕妇的疟疾感染和疾病，并提供有关抗疟疾药物的详细安全性和药代动力学信息。 怀孕的女人。

Each year, millions of women in areas of malaria transmission become pregnant and require protection from infection. Drugs currently used to prevent malaria in pregnancy are losing efficacy due to drug-resistant parasites. This Project will evaluate the safety, pharmacokinetics and efficacy of new regimens for Intermittent Preventive Treatment against pregnancy malaria (IPTp), including their long-term effects on offspring. In the studies proposed here, three new regimens (chlorproguanil-dapsone (LapDap); mefloquine; sulfadoxine-pyrimethamine (SP) + azithromycin) will be compared to the standard regimen (SP alone) for efficacy, pharmacokinetics and safety, including longterm effects on offspring. This proposed Project is based on the following hypotheses: New IPTp regimens will significantly increase birth weight and maternal hemoglobin compared to standard IPTp; New IPTp regimens will not increase the frequency of stillbirths, abortion, or fetal malformations, nor impair neurodevelopmental outcomes of offspring, compared to SP; Pharmacokinetics of antimalarial drugs in pregnant women will differ from those previously observed in nonpregnant individuals. This will be an open randomized controlled trial with four arms of IPTp. Specifically, the study will compare the clinical (maternal anemia, birth weight) and parasitological response (maternal parasitemia, placental parasitemia) to and the side effects of four IPTp regimens. The target population includes pregnant women presenting for routine antenatal care at the Morogoro Regional Hospital, where the ICDDR research center and training program will be based. The primary end-point for efficacy of the trial will be birth weight. Short-term toxicity will be assessed by careful monitoring for clinical, hematological, and biochemical abnormalities after dosing, and parasitologic response. Short and medium-term safety of IPTp will be assessed by maternal mortality, perinatal mortality, maternal complications, and clinically apparent abnormalities in the offspring. Longterm safety of IPTp regimens will be assessed in 3 year followup of offspring for hearing abnormalities or evidence of adverse neurodevelopmental consequences in standardized tests. Drug pharmacokinetics will be defined for each regimen using a Population-based approach to minimize blood sampling. The longterm objective of this Project is to identify more effective IPTp regimens to prevent malaria infection and disease in pregnant women, and to provide detailed safety and pharmacokinetics information on antimalarials for pregnant women.