Chronic Hypertension and Pregnancy-CHAP Clinical Coordinating Center

描述(申请人提供)：慢性高血压与妊娠(CHAP)项目是一项大型务实的多中心随机临床试验，旨在评估药物治疗妊娠期轻度慢性高血压(CHTN)的比较有效性和安全性。在妊娠期，CHTN是最常见的重大医学疾病，通常是轻微的(BP&lt；160/110 mm Hg)，并与不良结局相关，包括先兆子痫、围产期死亡、早产(PTB)和小于胎龄(SGA)婴儿(出生体重和出生体重10%)。虽然抗高血压治疗是普通人群的公共卫生优先事项，但包括美国妇产科医生学会(ACOG)在内的有关当局建议不要在妊娠期降血压，除非高血压很严重，即e160/110 mm Hg，因为疗效不确定，而且担心治疗可能实际上增加了SGA的风险。基于本文提供的支持性初步数据，我们假设CHTN在妊娠期进行抗高血压治疗，达到目前推荐给非妊娠高血压人群的140/90毫米汞柱的目标，将降低包括SGA在内的几种不良妊娠结局的风险。在为期6年的项目期间，我们由12个学术围产期中心(25个地点)组成的联盟将在怀孕早期确定4700名患有轻度CHTN和BP&lt；155/100 mmHg(提供者更愿意不治疗)的女性，并根据ACOG的建议随机接受降压治疗(使用拉贝洛尔)或根据ACOG建议进行管理(对更严重的CHTN进行降压治疗)。这些妇女将被跟踪，直到分娩后和产后3个月出院(预计将单独进行更长时间的跟踪；临时6个月的电话将考虑应急资金)。将解决以下具体目标：{1.1主要目标：确定妊娠期轻度CHTN的药物治疗是否符合标准BP目标&lt；140/90 mmHg，与标准治疗(根据ACOG：除非高血压严重，否则不治疗)相比，降低不良妊娠结局的风险，包括：1)严重的围产期综合结局(围产儿死亡、严重子痫前期、胎盘早剥或指示PTB&lt；35周)和2)SGA。1.2次级目标：i.更好地量化妊娠期轻度慢性HTN导致严重产妇心血管后果的风险，并确定治疗的影响。二、目的探讨分娩CHTN的最佳孕周，以减少母婴并发症。我们将对试验人群应用生存分析方法。三、收集和储存包括母血、脐带血和胎盘在内的生物标本，以供未来的生物学和生物物理研究，以了解降压治疗对患有轻度CHTN的孕妇的效果。四、评估妊娠期轻度CHTN的降压治疗是否能增加妊娠后对推荐治疗的依从性。

DESCRIPTION (provided by applicant): 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.