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; 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.

抽象的 瑞秋·辛基（Rachel G. Sinkey）博士是一位母亲医学专业人士，试图成为独立资助的 临床科学家专注于怀孕和产后的高血压和心血管疾病（CVD）疾病 时期。她寻求K23指导的研究奖来实现这一目标，并组建了一个世界团队 - 著名的专家在完成量身定制的五年职业发展和 指导的研究计划。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）填写公共卫生学位的理学硕士； 3） 获得当代高血压知识，以及4）获得战略赠款计划和写作方面的职业技能。 定制的职业发展计划将通过以指导的随机临床试验为重点 在先兆子痫上。先兆子痫（PE）是一种高血压疾病，发生在怀孕的后半部分， 使多达十二个怀孕的一人复杂化。 PE诊断后立即交付最少 产妇风险；但是，如果可能的话，如果妊娠是早产（<37周）以减少 早产的主要影响。尽管如此，母校或胎儿健康因素可能导致早产患者提供 PE包括：1）母体最终器官损伤或不受控制的严重高血压（称为严重PE）， 2）胎儿异常（涉及羊水，胎儿测试和/或子宫动脉多普勒）。美国人 心脏病学/美国心脏协会高血压指南提供怀孕高血压 美国产科医生学院的管理（ACOG）。 ACOG推荐 严重高血压（BP≥160/110 mmHg）的降压治疗，以避免急性心血管 并发症。另一方面，PE女性的非重度高血压治疗是有争议的 担心将动脉灌注降低到胎儿可能导致胎儿生长受损。也有关注 这种抗高血压疗法可能会掩盖严重的PE，从而导致孕产妇伤害。支持这些的证据 担忧是有限的，降压治疗是否安全延长怀孕是有限的，一个 新生儿益处的先决条件。鉴于知识中的这些关键差距，我们提出了“实现试验”， 非重生PE的早产患者的II期，标签RCT（n = 132）。 参与者将被随机分配1：1至：1）干预 - BP目标的抗高血压疗法<140/90 mmHg， 或2）通常的护理 - 仅当BP≥160/110 mmHg时，降压治疗。在AIM 1中，我们将确定是否治疗 为了实现BP目标<140/90 mmHg，延长了分娩的时间。在AIM 2中，我们将检查是否 干预降低了围产期和母体发病率。我们还将收集并存储血液以进行以后的学习 研究CVD生物标志物和内皮功能障碍。这项研究，伴随着 全面的职业发展计划将为富有成效的独立职业提供坚实的基础 在临床研究中，重点是怀孕和产后期间的高血压和心血管疾病。