Chronic Hypertension and Pregnancy (CHAP): Data Coordinating Center

描述（由申请人提供）：慢性高血压与妊娠（CHAP）项目是一项大型实用多中心随机临床试验，旨在评估妊娠期轻度慢性高血压（CHTN）药物治疗的相对有效性和安全性。妊娠期间，CHTN是最常见的主要疾病，通常为轻度（血压<160/110 mmHg），并与不良结局增加3-5倍相关，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<10个百分点）。虽然降压治疗是一般人群的公共卫生优先事项，但包括美国妇产科医师学会（ACOG）在内的权威机构建议，除非高血压严重（即e160/110 mm Hg），否则在妊娠期间不建议降压治疗，因为降压治疗的益处不确定，而且担心降压治疗实际上可能增加SGA的风险。基于本文提供的支持性初步数据，我们假设妊娠期间对CHTN进行降压治疗，使其达到目前推荐的非妊娠高血压人群<140/90 mmHg的目标，将降低包括SGA在内的几种不良妊娠结局的风险。在6年的项目期间，我们的12个学术围产期中心（25个站点）将在妊娠早期确定4700名轻度CHTN和标准血压<155/100 mmHg（提供者更愿意不治疗）的妇女，并将她们随机分配到降压治疗（使用拉贝他洛尔）或根据ACOG建议进行管理（降压治疗更严重的CHTN）。将对这些妇女进行随访，直到分娩后出院，并随访至产后3个月（长期随访，包括为期6个月的临时电话随访，预计将作为单独的相关项目进行）。1.1主要目的：确定妊娠期轻度CHTN的药物治疗是否达到标准血压目标<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，可降低不良妊娠结局的风险，包括：1)严重的围产期综合结局（围产期死亡、严重先兆子痫、胎盘早剥或指示性PTB <35周）和2)SGA。1.2次要目的：1.更好地量化与轻度CHTN相关的孕妇罕见心血管风险（包括死亡、心肌梗死、中风、肾功能衰竭）在妊娠期间的发生率，并检查治疗效果。2。探讨CHTN妇女的最佳胎龄，以减少产妇和围产期并发症。3。收集和保存孕妇血液、脐带血和胎盘活检等生物标本，为今后的生物学和生物物理研究提供依据，以了解妊娠期降压治疗的效果。iv.评估妊娠期抗高血压治疗是否会增加妊娠后治疗依从性。本应用程序总结了配套应用程序的试用，并描述了DCC提供全面服务的电子数据采集、报告和数据管理服务的操作。这些数据管理服务的范围包括：数据库规范、编辑检查编程、数据管理计划开发和维护、正在进行的手动数据审查和查询管理、医疗编码以及数据清理和锁定。具体监测观察到的血压和血压控制以及安全监测将是一个主要的努力。此外，DCC将为DSMB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.