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

四种 IPTP 方案对孕妇和孕妇的疗效和安全性比较

• 批准号: 6969061
• 负责人: Theonest Mutabingwa
• 金额: $ 45.86万
• 依托单位: SEATTLE BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969061
• 关键词: Africa; anemia; antimalarial agents; azithromycin; chemoprevention; clinical trials; cooperative study; dapsone; developmental neurobiology; drug screening /evaluation; embryo /fetus death; embryo /fetus pharmacology; hemoglobin; human birth weight; human mortality; human pregnant subject; human therapy evaluation; labor complications; longitudinal human study; malaria; microorganism disease chemotherapy; patient oriented research; pharmacokinetics; pregnancy infection; spontaneous abortion; women' s health

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.

每年，疟疾传播地区有数百万妇女怀孕，需要保护免受感染。目前用于预防妊娠期疟疾的药物由于抗药性寄生虫而失去效力。本项目将评价妊娠期疟疾间歇预防治疗（IPTp）新方案的安全性、药代动力学和疗效，包括其对后代的长期影响。在这里提出的研究中，三种新的方案（氯丙胍-氨苯砜（LapDap）;甲氟喹;磺胺嘧啶-乙胺嘧啶（SP）+ 阿奇霉素）与标准方案（单独使用SP）的疗效、药代动力学和安全性，包括对后代的长期影响。该项目基于以下假设：与标准IPTp相比，新的IPTp方案将显著增加出生体重和母体血红蛋白;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局;抗疟药物在妊娠女性中的药代动力学将不同于先前在非妊娠个体中观察到的药代动力学。这将是一项开放、随机、对照试验，包含4个IPTp组。具体而言，本研究将比较四种IPTp方案的临床（母体贫血、出生体重）和寄生虫学应答（母体寄生虫血症、胎盘寄生虫血症）以及副作用。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研究中心和培训方案将设在那里。主要终点 试验的有效性将是出生体重。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应答来评估短期毒性。将通过孕产妇死亡率、围产期死亡率、孕产妇并发症和后代临床明显异常来评估IPTp的短期和中期安全性。将在后代3年随访中评估IPTp方案的长期安全性， 听力异常或在标准化测试中有不良神经发育后果的证据。将使用基于人群的方法定义每种方案的药物药代动力学，以尽量减少血液采样。该项目的长期目标是确定更有效的IPTp方案，以预防孕妇的疟疾感染和疾病，并提供关于抗疟药物的详细安全性和药代动力学信息， 孕妇