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

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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.