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

四种 IPTP 方案对孕妇的疗效和安全性比较

• 批准号: 7491573
• 负责人: Theonest Mutabingwa
• 金额: $ 60.64万
• 依托单位: SEATTLE BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7491573
• 关键词: Accounting; Adverse effects; Africa; Age; Anemia; Antimalarials; Area; Azithromycin; Biochemical; Birth Weight; Blood specimen; Caring; Cessation of life; Chemoprophylaxis; Clinical; Cohort Studies; Dapsone; Disease; Dose; Drug Kinetics; Drug resistance; Drug usage; End Point; Frequencies; Gravidity; Hearing; Hemoglobin; Hospitalization; Hospitals; Immune; Individual; Infant; Infection; International; Life; Long-Term Effects; Low Birth Weight Infant; Malaria; Maternal Mortality; Measures; Mefloquine; Monitor; Mothers; Newborn Infant; Outcome; Parasite resistance; Parasitemia; Participant; Patient currently pregnant; Perinatal mortality demographics; Pharmaceutical Preparations; Population; Pregnancy; Pregnant Women; Preventive; Public Health; Pyrimethamine; Pyrimethamine-Sulfadoxine; Randomized Controlled Trials; Rate; Reporting; Research; Research Personnel; Risk; Safety; Schedule; Scientist; Standards of Weights and Measures; Sulfadoxine; Tanzania; Target Populations; Testing; Time; Toxic effect; Training Programs; Treatment Protocols; Upper arm; Woman; World Health Organization; abortion; base; chlorproguanil; cohort; efficacy trial; fetal; improved; infancy; infant outcome; malformation; mefloquine-sulfadoxine-pyrimethamine; next generation; prevent; response; stillbirth; transmission process; uptake

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.

在疟疾传播地区，每年有数百万妇女怀孕，需要保护她们免受感染。目前用于预防妊娠期疟疾的药物由于耐药寄生虫正在失去效力。本项目将评估妊娠期疟疾间歇预防治疗（IPTp）新方案的安全性、药代动力学和有效性，包括对后代的长期影响。在本文提出的研究中，三种新方案(氯丙胍-氨苯砜（LapDap）；甲氟喹合成;磺胺多辛-乙胺嘧啶(SP) +