Early Double Low-Dose Aspirin to Reduce Preeclampsia and Miscarriage: a Global Approach RCT

早期双倍低剂量阿司匹林减少先兆子痫和流产：全球方法随机对照试验

• 批准号: 10711793
• 负责人: Kurt T Barnhart
• 金额: $ 69.23万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-10 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711793
• 关键词: Affect; Area; Aspirin; Biometry; Cessation of life; Clinical; Clinical Trials; Conceptions; Dangerousness; Data; Discipline of obstetrics; Dose; Double-Blind Method; Early Diagnosis; Ensure; First Pregnancy Trimester; Guidelines; Gynecologic; Health; Hospitals; Hypertension; Intervention; Intervention Trial; Literature; Machine Learning; Medicine; Minority; Monitor; Morbidity - disease rate; Outcome; Patient Recruitments; Patients; Pennsylvania; Perinatal; Perinatal Epidemiology; Persons; Phenotype; Philadelphia; Placebos; Placentation; Population; Population Heterogeneity; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Tests; Pregnancy loss; Prevention; Primary Prevention; Protocols documentation; Recommendation; Research; Risk; Sampling; Shoulder; Spontaneous abortion; System; Time; Underrepresented Minority; United States Preventative Services Task Force; Universities; Vascularization; Woman; black women; clinical care; dosage; follow-up; implantation; improved; machine learning method; metropolitan; novel; optimal treatments; pregnancy disorder; pregnancy hypertension; pregnant; prevent; psychologic; randomized trial; recruit; reproductive; reproductive outcome; secondary outcome; standard of care; targeted treatment

Project Summary Aspirin is currently recommended during pregnancy to help prevent preeclampsia, and also shows promise for protecting against pregnancy loss. Preeclampsia is a dangerous complication of pregnancy that puts both the pregnant person and their baby at risk of serious morbidity and death, and pregnancy loss is the most common complication of pregnancy estimated to affect 20-30% of all conceptions. Current clinical guidelines from the U.S. Preventive Services Task Force (USPSTF) recommend the use of daily “baby” aspirin (81 mg), begun at 12 weeks' gestation, to prevent preeclampsia. However, data suggest that even earlier initiation of aspirin and at higher doses may result in greater protection. Furthermore, initiating aspirin immediately upon pregnancy recognition may maximize effects on preeclampsia while also providing the added opportunity to prevent pregnancy loss. Therefore, we propose to conduct a randomized trial to investigate whether daily “double low- dose” aspirin therapy (162 mg per day) initiated at the time of first positive pregnancy test (up to 6 weeks' gestation) may help prevent both outcomes. Clinical recruitment of participants through the follow-up of all initial pregnancy tests throughout the Penn Medicine system will ensure feasibility for early detection of pregnancy, enabling pregnancy loss monitoring and initiation of the trial intervention. The findings from this study will provide essential, high-quality evidence in a diverse sample of U.S. pregnant people to inform potential changes to clinical guidelines for aspirin use in pregnancy. We will (Aim 1) determine the effect of aspirin treatment (dose 162 mg) initiated upon positive pregnancy test (up to 6 weeks' gestation) compared to standard of care (dose 81 mg initiated at 12 weeks' gestation) on preeclampsia in a diverse population; (Aim 2) determine the effect of aspirin treatment (dose 162 mg) initiated upon positive pregnancy test (up to 6 weeks' gestation) compared to standard of care (dose 81 mg initiated at 12 weeks' gestation) on pregnancy loss in a diverse population; and (Aim 3) identify phenotypes who may benefit most from “double low-dose” aspirin (162 mg) begun soon after conception, using machine learning, to inform more targeted therapy for optimal overall pregnancy outcomes. As a safe, affordable intervention, these findings will have immediate translational value to improve reproductive outcomes in pregnant patients, including minorities such as Black women vastly underrepresented in current data.

项目摘要 阿司匹林目前被推荐在怀孕期间使用，以帮助预防先兆子痫， 防止流产。先兆子痫是一种危险的妊娠并发症， 孕妇及其婴儿面临严重的发病和死亡风险，流产是最常见的 据估计，怀孕并发症影响到所有怀孕的20-30%。目前的临床指南， 美国预防服务工作组（USPSTF）建议每天使用“婴儿”阿司匹林（81毫克），从 怀孕12周，以防止先兆子痫。然而，数据表明，即使更早开始服用阿司匹林， 在更高的剂量下可能会产生更大的保护作用。此外，怀孕后立即服用阿司匹林 识别可以最大限度地提高对先兆子痫的影响，同时也提供了额外的机会， 流产因此，我们建议进行一项随机试验，以调查每日“双低- 剂量”阿司匹林治疗（162 mg/天）开始时，首次阳性妊娠试验（长达6周） 妊娠）可能有助于防止这两种结果。通过对所有参与者进行随访， 整个宾州医学系统的初始妊娠试验将确保早期发现的可行性。 妊娠，能够监测妊娠丢失并启动试验干预。这一发现 这项研究将在不同的美国孕妇样本中提供重要的高质量证据， 怀孕期间使用阿司匹林的临床指南可能发生变化。我们将（目标1）确定 妊娠试验阳性时开始阿司匹林治疗（剂量162 mg）（妊娠6周内）， 在不同人群中对先兆子痫进行标准治疗（妊娠12周时开始剂量为81 mg）;（目标2） 确定阿司匹林治疗（剂量162 mg）对妊娠试验阳性（长达6周）的影响 妊娠）与标准治疗（妊娠12周时开始给药81 mg）相比， 不同人群;（目的3）确定哪些表型可能从“双倍低剂量”阿司匹林中获益最大（162 mg）在受孕后不久开始，使用机器学习，为更有针对性的治疗提供信息， 妊娠结局。作为一种安全、负担得起的干预措施，这些发现将具有直接的转化价值。 改善怀孕患者的生殖结果，包括黑人妇女等少数民族， 在目前的数据中被低估了。