Chronic Hypertension and Pregnancy-CHAP Clinical Coordinating Center

项目描述（申请人提供）：慢性高血压与妊娠（CHTN）项目是一项大型实用多中心随机临床试验，旨在评价妊娠期轻度慢性高血压（CHTN）药物治疗的比较有效性和安全性。在妊娠期间，CHTN是最常见的主要医学病症，最常见的是轻度（BP <160/110 mmHg），并且与包括先兆子痫、围产期死亡、早产（PTB）和小于胎龄儿（SGA）婴儿（出生体重<第10百分位数）在内的不良结局增加3-5倍相关。鉴于抗高血压治疗是一般人群的公共卫生优先事项，包括美国妇产科医师学会（ACOG）在内的权威机构建议在妊娠期间不要使用降压治疗，除非高血压严重，即，e160/110 mm Hg，因为不确定的好处和担心治疗可能会增加SGA的风险。基于本文提供的支持性初步数据，我们假设妊娠期间CHTN的降压治疗目标<140/90 mmHg（目前推荐用于非妊娠高血压人群）将降低几种不良妊娠结局（包括SGA）的风险。在为期6年的项目期间，我们的12个学术围产期中心（25个站点）的联盟将确定4700名患有轻度CHTN和BP<155/100 mmHg（提供者更舒适不治疗）的早期妊娠妇女，并将其随机分配到抗高血压治疗（使用拉贝洛尔）或根据ACOG建议的管理（更严重的CHTN的抗高血压治疗）。将对女性进行随访，直至分娩后出院和产后3个月（预计单独进行更长时间的随访;将考虑为6个月的中期电话随访提供应急资金）。将讨论以下具体目的：} {1.1主要目的：确定与标准管理相比，妊娠期轻度CHTN的药物治疗是否达到标准化BP目标<140/90 mmHg（根据ACOG：除非高血压严重，否则不进行治疗），降低不良妊娠结局的风险，包括：1）严重的围产期复合结局（围产期死亡、严重的先兆子痫、胎盘脱垂或指示的PTB <35周）和2）SGA。1.2次要目标：i。更好地量化妊娠期间与轻度CHTN相关的重度母体心血管结局的风险，并确定治疗的影响。二.探讨CHTN孕妇分娩的最佳胎龄，以减少母体和围生期并发症。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，用于未来的生物学和生物物理学研究，以了解抗高血压治疗对轻度CHTN孕妇的影响。四.评估妊娠期间轻度CHTN的降压治疗是否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.