Improving Neonatal health Through Rapid malaria testing in Early Pregnancy with high-sensitivity Diagnostics (INTREPiD)

通过妊娠早期快速疟疾检测和高灵敏度诊断来改善新生儿健康 (INTREPiD)

• 批准号: 10405395
• 负责人: Steve Myer Taylor
• 金额: $ 140.77万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10405395
• 关键词: Address; Africa South of the Sahara; Aftercare; Antimalarials; Area; Clinic; Clinical; Clinical Trials; Collaborations; Communicable Diseases; Complement; Country; Data; Democratic Republic of the Congo; Detection; Development; Diagnostic Sensitivity; Diagnostic tests; Discipline of obstetrics; Dose; Drug Kinetics; Enrollment; Epidemiology; Fetal Growth; First Pregnancy Trimester; Goals; Guidelines; Infant; Infection; Institution; Intercept; Intervention; Kenya; Left; Low Birth Weight Infant; Low Prevalence; Malaria; Malawi; Measures; Modeling; Neonatal Mortality; Neonatology; Outcome; Parasites; Placentation; Plasmodium falciparum; Population; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prevention strategy; Preventive therapy; Prophylactic treatment; Pyrimethamine-Sulfadoxine; Randomized; Rapid diagnostics; Reporting; Resource-limited setting; Risk; Safety; Schedule; Second Pregnancy Trimester; Small for Gestational Age Infant; Testing; Third Pregnancy Trimester; Treatment Efficacy; Treatment Protocols; Update; Woman; adverse pregnancy outcome; antenatal; artemether; benflumetol; cohort; density; design; early pregnancy; effective therapy; efficacy testing; experience; fetal loss; high risk population; improved; infant death; infection risk; innovation; malaria infection; mathematical model; neonatal death; neonatal health; novel strategies; pharmacokinetics and pharmacodynamics; prenatal; prevent; primary outcome; screening; success; transmission process; treatment as usual; treatment strategy

Project Summary/Abstract Newborn health has improved globally but there remains a critical need in resource-limited settings to reduce neonatal mortality. Nearly all infant deaths in sub-Saharan Africa occur in babies that are small or low birthweight, which often result from antenatal infections with Plasmodium falciparum. These malaria effects can be partially mitigated by pregnancy-specific measures including the administration of monthly antenatal doses of sulfadoxine-pyrimethamine as intermittent preventive therapy during pregnancy (IPTp-SP), but these are not typically implemented until the 2nd trimester, and so do not mitigate the risks of infection in the 1st trimester. It is now feasible to include 1st trimester screening for malaria parasites owing to: i) updated WHO guidelines that recommend an expended schedule of 8 ANC contacts, with the first prior to 12 weeks gestation, ii) the availability of high-sensitivity malaria rapid diagnostic tests (HS-RDT) with enhanced detection of low-density infections, and iii) accumulated safety data that enable the use of Artemether-Lumefantrine (AL) for malaria treatment in the 1st trimester. We hypothesize that, compared to women who enter ANC and receive usual care, women who are screened in the 1st trimester with an HS-RDT will have a lower prevalence of a poor pregnancy outcome, and we will test this through the Improving Neonatal health Through Rapid malaria testing in Early Pregnancy with high-sensitivity Diagnostics (INTREPiD) study in Western Kenya and the Democratic Republic of the Congo (DRC). In Aim 1, the INTREPiD study will enroll women in the 1st trimester and randomize them 1:1 to usual care or to screening with an HS-RDT followed by treatment of positives with AL, and then follow them through delivery. Following the 1st trimester intervention, all women will receive usual ANC, including IPTp-SP. The primary outcome will be the composite outcome of low birthweight, small-for- gestational age, preterm birth, fetal loss, or neonatal death. In Aim 2, we will measure the therapeutic efficacy and pharmacokinetics of AL administration in the 1st trimester through a population PK study following standard AL dosing and compare PK parameters with historical controls. In Aim 3, we will use trial data to model the potential incremental benefits of enhanced-sensitivity diagnostics and alternate treatment regimens on the risk of an adverse pregnancy outcome in order to maximize the impact of our trial data. Collectively these data will guide the development and implementation of fresh approaches to intercept parasites early in pregnancy and thereby enhance pregnancy outcomes and newborn health.

项目摘要/摘要 新生儿健康在全球范围内有所改善，但在资源有限的环境中仍然需要减少资源有限的设置 新生儿死亡率。撒哈拉以南非洲的几乎所有婴儿死亡都发生在小或低的婴儿中 出生体重通常是由于恶性疟原虫的产前感染而引起的。这些疟疾的影响可以 通过特定于妊娠的措施来部分缓解，包括每月剂量的给药 磺胺毒素 - 甲胺作为妊娠期间间歇性预防疗法（IPTP-SP）的 通常在第二个三个月之前实施，因此不要减轻第一个孕期感染的风险。它 现在可以包括：i）更新了谁的指导原则 建议在12周之前的第一个ANC联系时间表进行8个ANC联系人，ii） 高密度诊断测试（HS-RDT）的可用性增强了低密度检测 感染，以及iii）积累的安全数据，使疟疾能够使用手指液（AL） 在孕期治疗。与进入ANC并接受常规的女性相比，我们假设这一点 关心，在第一个三个月筛查的女性HS-RDT的患病率较低 怀孕的结果，我们将通过快速疟疾测试来改善新生儿健康来进行测试 在怀孕早期，肯尼亚西部和民主的高敏性诊断（Intrepid）研究 刚果共和国（DRC）。在AIM 1中，这项无畏的研究将在第一个妊娠中注册妇女，并 将它们1：1随机照顾或使用HS-RDT进行筛查，然后用Al的阳性处理 然后跟随他们进行交付。在孕期干预之后，所有妇女都将接受常规 ANC，包括IPTP-SP。主要结果将是低出生体重，小小的综合结果 胎龄，早产，胎儿丧失或新生儿死亡。在AIM 2中，我们将测量治疗功效 通过遵守标准的人群PK研究，第1个三个月的AL管理药代动力学 Al剂量和比较PK参数与历史控制。在AIM 3中，我们将使用试用数据来建模 增强敏感性诊断和替代治疗方案的潜在增量益处 不良怀孕结果，以最大程度地提高我们的试验数据的影响。这些数据总共 指导新方法的开发和实施 从而提高妊娠结局和新生儿健康。