Chronic Hypertension and Pregnancy (CHAP): Data 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)，并与不良结局有关，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识别4700名患有轻度CHTN和标准化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(针对更严重的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(长期跟踪，包括临时的6个月电话，预计是一个单独的相关项目)。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的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，是否降低了不良妊娠结局的风险，包括：1)严重的围产期综合结局(围产期死亡、重度先兆子痫、胎盘早剥或显示为PTB&lt；35周)和2)SGA。1.2次要目标：i.更准确地量化妊娠期与轻度慢性HTN(包括死亡、心肌梗死、中风、肾功能衰竭)有关的罕见母亲心血管风险的发生率，并检查治疗效果。二、目的探讨CHTN产妇的最佳孕龄，以减少母儿并发症。三、收集和储存生物标本，包括母血、脐带血和胎盘活检，以供将来的生物学和生物物理研究，以了解妊娠期降压治疗的效果。四、评价妊娠期抗高血压治疗是否能提高妊娠后的治疗依从性。本申请总结了配套应用程序的试用情况，并描述了数据中心为提供全面服务的电子数据捕获、报告和数据管理服务而进行的操作。这些数据管理服务的范围包括：数据库规范、编辑检查编程、数据管理计划的制定和维护、持续的人工数据审查和查询管理、医疗编码以及数据清理和锁定。对观察到的血压和血压控制的具体监测以及安全监测将是一项重大努力。此外，DCC将提供统计分析(考虑到实用设计)和报告，其中包括数据摘要、表格和对DSMB的统计分析。

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 is 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 standardized 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 (long-term follow-up, including an interim 6-month phone call, is anticipated as a separate related project). 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 incidence during pregnancy of rare maternal cardiovascular risks associated with mild CHTN (including death, myocardial infarction, stroke, renal failure) and examine the effect of treatment. ii. To investigate the optial gestational age to deliver women with CHTN in order to minimize maternal and perinatal complications. iii. To collect and store biospecimens including maternal blood, cord blood and placenta biopsy for future biological and biophysical studies to understand the effects of antihypertensive therapy during pregnancy. iv. To evaluate whether antihypertensive treatment during pregnancy increases post-pregnancy treatment adherence. This application summarizes the trial of the companion application and describes the operations of the DCC to provide full service electronic data capture, reporting and data management services. The extent of these data management services include: database specification, edit check programming, data management plan development and maintenance, ongoing manual data review and query management, medical coding and data cleaning and locking. Specific monitoring of observed blood pressures and blood pressure control along with safety monitoring will be a major endeavor. In addition, the DCC will provide statistical analysis (considering the pragmatic design) and reports which include the data summaries, tables, and statistical analyses for the DSMB.