The ACHIEVE Trial: Achieving longer gestation in preeclampsia via antihypertensive therapy.

ACHIEVE 试验：通过抗高血压治疗实现先兆子痫患者妊娠时间延长。

• 批准号: 10448650
• 负责人: Rachel G Sinkey
• 金额: $ 19.14万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10448650
• 关键词: 37 weeks gestation; Acute; Acute Kidney Failure; Admission activity; Affect; Alabama; American; American College of Obstetricians and Gynecologists; American Heart Association; Amniotic Fluid; Antihypertensive Agents; Arteries; Award; Biological Markers; Birth; Blood; Blood Pressure; Bronchopulmonary Dysplasia; Cardiology; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Clinical; Clinical Research; Clinical Trials; Conduct Clinical Trials; Conflict (Psychology); Custom; Data; Development Plans; Diagnosis; Eclampsia; Enrollment; Fetal Death; Fetal Growth Retardation; Fetal health; Fetus; Foundations; Funding; Future; Goals; Grant; Guidelines; Heart failure; Hypertension; Intensive Care Units; Intervention; Knowledge; Lead; Life; Liver Dysfunction; Masks; Master of Science; Maternal Health; Maternal Mortality; Maternal-fetal medicine; Mentors; Mentorship; Mothers; Multi-Institutional Clinical Trial; Multiple Organ Failure; Necrotizing Enterocolitis; Neonatal; Neonatal Intensive Care Units; Neonatal Mortality; Organ; Outcome; Participant; Pathway interactions; Patients; Perfusion; Perinatal; Perinatal mortality demographics; Pharmaceutical Preparations; Phase; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnant Women; Premature Birth; Professional Competence; Public Health; Pulmonary Edema; Randomized; Randomized Clinical Trials; Reproductive Health; Research; Retinopathy of Prematurity; Safety; Scientist; Small for Gestational Age Infant; Stroke; Testing; Thrombocytopenia; Time; Training; University resources; Uterus; Woman; Writing; adverse maternal outcomes; cardiovascular disorder risk; cardiovascular endothelium; career; career development; college; design; disability; endothelial dysfunction; fetal; hazard; hospital readmission; hypertension control; hypertension treatment; improved; interest; intraventricular hemorrhage; lifetime risk; maternal morbidity; maternal risk; maternal serum; neonatal outcome; neonate; offspring; open label; perinatal health; perinatal morbidity; pregnancy hypertension; premature; research study; skills; treatment arm; treatment as usual; usual care arm

ABSTRACT Dr. Rachel G. Sinkey is a maternal-fetal medicine subspecialist who seeks to become an independently funded clinician-scientist focused on hypertension and cardiovascular (CVD) disease in pregnancy and the postpartum period. She seeks a K23 Mentored Research Award to realize this goal and has assembled a team of world- renowned experts to provide mentorship as she completes a tailored, five-year career development and mentored research plan. In the comprehensive career development plan the candidate will: 1) obtain skills to independently design and conduct clinical trials; 2) complete a Master of Science in Public Health degree; 3) attain contemporary hypertension knowledge, and 4) obtain career skills in strategic grant planning and writing. The customized career development plan will be accompanied by a mentored randomized clinical trial focused on preeclampsia. Preeclampsia (PE) is a hypertensive disorder that occurs in the second half of pregnancy, complicating up to one in twelve pregnancies. Delivery immediately following PE diagnosis carries the least maternal risk; however, when possible, delivery is delayed if the gestation is preterm (<37 weeks) to decrease major effects of prematurity. Despite this, maternal or fetal health factors may lead to delivery of a preterm patient with PE including: 1) maternal end-organ damage or uncontrolled severe hypertension (known as severe PE), and 2) fetal abnormalities (involving amniotic fluid, fetal testing and/or uterine artery Dopplers). The American College of Cardiology/American Heart Association Hypertension Guideline defers pregnancy hypertension management to the American College of Obstetricians and Gynecologists (ACOG). ACOG recommends antihypertensive treatment for severe hypertension (BP ≥160/110 mmHg), to avoid acute cardiovascular complications. On the other hand, treatment of non-severe hypertension in women with PE is controversial, due to concerns that lowering arterial perfusion to the fetus may lead to impaired fetal growth. There is also concern that anti-hypertensive therapy may mask severe PE, leading to maternal harm. Evidence supporting these concerns is limited, and it is unknown whether antihypertensive treatment safely prolongs pregnancy, a prerequisite for neonatal benefit. Given these critical gaps in knowledge, we propose “The ACHIEVE Trial”, a phase II, open-label RCT (N=132) of antihypertensive treatment in preterm patients with non-severe PE. Participants will be randomized 1:1 to: 1) intervention – anti-hypertensive therapy for BP goal <140/90 mmHg, or 2) usual care – antihypertensive therapy only if BP ≥160/110 mmHg. In Aim 1 we will determine if treatment to achieve a BP goal <140/90 mmHg prolongs mean time to delivery. In Aim 2 we will examine whether the intervention reduces perinatal and maternal morbidity. We will also collect and store blood for future studies investigating CVD biomarkers and endothelial dysfunction. This research study, accompanied by a comprehensive career development plan, will provide a strong foundation for a productive independent career in clinical research focused on hypertension and cardiovascular disease in pregnancy and the postpartum period.

摘要 博士瑞秋·G Sinkey是一名母胎医学亚专家，他寻求成为一名独立资助的 临床科学家，专注于妊娠期和产后高血压和心血管（CVD）疾病 期她寻求K23指导研究奖，以实现这一目标，并组建了一个团队的世界- 在她完成量身定制的五年职业发展计划时， 指导研究计划。在全面的职业发展计划中，候选人将：1）获得技能， 独立设计和进行临床试验; 2）完成公共卫生硕士学位; 3） 获得当代高血压知识，以及4）获得战略拨款规划和写作的职业技能。 定制的职业发展计划将伴随着一个指导性的随机临床试验， 关于先兆子痫先兆子痫（PE）是一种发生在妊娠后半期的高血压疾病， 每12次怀孕中就有一次会出现并发症PE诊断后立即分娩携带最少 母体风险;然而，如果可能，如果妊娠早产（<37周），则延迟分娩，以减少 早产的主要影响。尽管如此，母亲或胎儿的健康因素可能会导致早产患者的分娩 PE包括：1）母体终末器官损伤或不受控制的重度高血压（称为重度PE）， 和2）胎儿异常（涉及羊水、胎儿测试和/或子宫动脉多普勒）。美国 心脏病学院/美国心脏协会高血压指南推迟妊娠高血压 美国妇产科医师学会（ACOG）。ACOG建议 重度高血压（BP ≥160/110 mmHg）的降压治疗，避免急性心血管 并发症另一方面，治疗非重度高血压女性PE是有争议的，由于 担心降低胎儿动脉灌注可能导致胎儿生长受损。也有人担心 抗高血压治疗可能会掩盖严重的PE，导致母体伤害。支持这些的证据 关注是有限的，抗高血压治疗是否能安全地阻止妊娠， 新生儿福利的先决条件。鉴于这些关键的知识差距，我们建议“ACHIEVE试验”， 一项在非重度PE早产儿患者中进行抗高血压治疗的II期、开放标签RCT（N=132）。 参与者将以1：1的比例随机分配到：1）干预-降压治疗，目标血压<140/90 mmHg， 或2）常规治疗-仅当BP ≥160/110 mmHg时进行降压治疗。在目标1中，我们将确定治疗是否 达到BP目标<140/90 mmHg/平均分娩时间。在目标2中，我们将研究 干预措施降低了围产期和孕产妇发病率。我们也会收集和储存血液，以备将来研究之用 研究CVD生物标志物和内皮功能障碍。这项研究，伴随着一 一个全面的职业发展计划，将为一个富有成效的独立职业生涯提供坚实的基础 临床研究主要集中在妊娠期和产后期的高血压和心血管疾病。