Chronic Hypertension and Pregnancy-CHAP Clinical Coordinating Center

项目摘要/摘要 慢性高血压和妊娠(CHAP)项目是一项大型务实的多中心随机临床试验 评价药物治疗轻度慢性阻塞性肺疾病的有效性和安全性的试验设计 妊娠期高血压(CHTN)。在怀孕期间，CHTN是最常见的重大医学疾病， 大多数是轻微的(BP&lt；160/110毫米汞柱)，并与不良后果增加3-5倍相关，包括 先兆子痫、围产儿死亡、早产(PTB)和小于胎龄儿(出生体重 &lt；10%)。尽管抗高血压治疗是普通人群的公共卫生优先事项， 包括美国妇产科医生学会(ACOG)在内的当局建议不要 妊娠期降压治疗，除非高血压很严重，即E160/110毫米汞柱，因为 不确定的益处以及对治疗可能实际上增加SGA风险的担忧。基于支持性 在此提供的初步数据中，我们假设CHTN在妊娠期的降压治疗 目前推荐给非妊娠高血压人群的目标&lt；140/90毫米汞将降低 几种不良妊娠结局的风险，包括SGA。在6年的项目期内，我们的财团 在12个学术围产期中心(25个地点)中，将确定4700名患有轻度慢性HTN和BP&lt；155/100毫米汞柱的妇女 (哪些提供者更愿意不接受治疗)，并将他们随机分配到 抗高血压治疗(使用拉贝洛尔)或根据ACOG的建议进行管理 (对更严重的CHTN进行降压治疗)。将对这些妇女进行追踪，直到她们出院。 {分娩后和产后最多3个月的医院(预计将另行进行更长时间的随访；应急资金 将考虑进行为期6个月的临时电话通话)。将实现以下具体目标： (1.1主要目的：确定妊娠期轻度CHTN的药物治疗是否符合标准血压) 目标&lt；140/90毫米汞柱，与标准管理相比(根据ACOG：除非高血压是 严重)，降低不良妊娠结局的风险，包括：1)严重的围产期综合结局 (2)重度子痫前期(围产儿死亡、重度子痫前期、胎盘早剥或胎盘早剥；35周)； 1.2次要目标： I.为了更好地量化与轻度慢性HTN相关的严重孕产妇心血管后果的风险 并确定治疗对妊娠的影响。 二、探讨分娩CHTN的最佳孕周，以最大限度地减少母婴传播的风险。 围产期并发症。我们将对试验人群应用生存分析方法。 三、收集和储存生物标本，包括母血、脐带血和胎盘，以供未来生物 和生物物理研究，以了解降压治疗对轻度高血压孕妇的影响 CHTN. 四、评估妊娠期轻度CHTN的降压治疗是否会增加妊娠后的血压 坚持推荐的治疗方法。

PROJECT SUMMARY/ABSTRACT The Chronic Hypertension and Pregnancy (CHAP) project is a large pragmatic multi-center randomized clinical trial designed to evaluate the comparative effectiveness and safety of pharmacologic treatment of mild chronic hypertension (CHTN) in pregnancy. During pregnancy, CHTN is the most common major medical disorder, most often mild (BP <160/110 mmHg), and associated with a 3-5 fold increase in adverse outcomes including preeclampsia, perinatal death, preterm birth (PTB) and small for gestational age (SGA) infants (birth weight <10th percentile). Whereas antihypertensive therapy is a public health priority for the general population, authorities, including the American College of Obstetricians and Gynecologists (ACOG), recommend against BP lowering therapy during pregnancy unless hypertension is severe, i.e., e160/110 mm Hg, because of uncertain benefits and the concern that therapy may actually increase the risk of SGA. Based on supportive preliminary data presented herein, we hypothesize that antihypertensive therapy for CHTN during pregnancy to the goal <140/90 mmHg as currently recommended for the non-pregnant hypertensive population, will reduce the risk of several adverse pregnancy outcomes including SGA. During a 6-year project period, our consortium of 12 academic perinatal centers (25 sites), will identify 4700 women with mild CHTN and BP<155/100 mmHg (which providers are more comfortable not treating) in early pregnancy and randomize them to either antihypertensive therapy (using labetalol) or to management according to ACOG recommendations (antihypertensive therapy for more severe CHTN). The women will be followed-up until discharge from the {hospital after delivery and up to 3 months postpartum (longer follow-up is anticipated separately; contingency funds will be considered for interim 6-month phone call). The following Specific Aims will be addressed: } {1.1 Primary Aim: To determine if pharmacologic treatment of mild CHTN in pregnancy to a standardized BP} goal<140/90 mmHg, compared with standard management (per ACOG: no treatment unless hypertension is severe), reduces the risk of adverse pregnancy outcomes including: 1) a severe perinatal composite outcome (perinatal death, severe preeclampsia, placental abruption or indicated PTB <35 weeks) and 2) SGA. 1.2 Secondary Aims: i. To better quantify the risks of severe maternal cardiovascular outcomes associated with mild CHTN during pregnancy and determine the impact of treatment. ii. To investigate the optimal gestational age to deliver women with CHTN in order to minimize maternal and perinatal complications. We will apply survival analysis methods to the trial population. iii. To collect and store biospecimens including maternal blood, cord blood and placentas for future biological and biophysical studies to understand the effects of antihypertensive therapy in pregnant women with mild CHTN. iv. To assess whether antihypertensive treatment of mild CHTN during pregnancy increases post-pregnancy adherence to recommended therapy.