Chronic Hypertension and Pregnancy-CHAP Clinical Coordinating Center

慢性高血压与妊娠-CHAP临床协调中心

• 批准号: 9093832
• 负责人: ALAN THEVENET N. TITA
• 金额: --
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9093832
• 关键词: Abruptio Placentae; Acute Kidney Failure; Address; Adherence; American College of Obstetricians and Gynecologists; Antihypertensive Agents; Benefits and Risks; Biological; Birth Weight; Blood; Blood flow; Cardiovascular system; Cessation of life; Chronic; Clinical; Clinical Trials Data Monitoring Committees; Conflict (Psychology); Contingency Fund; Data; Discipline of obstetrics; Disease; Equipoise; Evaluation; Fetal Death; Fetal Growth; Follow-Up Studies; Frequencies; Future; General Population; Gestational Age; Goals; Hospitals; Hypertension; Infant; Joints; Kidney; Labetalol; Lead; Measurement; Medical; Methods; Monitor; National Heart, Lung, and Blood Institute; Newborn Infant; Outcome; Participant; Perinatal; Perinatal mortality demographics; Pharmacological Treatment; Pharmacology; Phonation; Placenta; Policies; Population; Postpartum Period; Pre-Eclampsia; Pregnancy; Pregnant Women; Premature Birth; Provider; Public Health; Pulmonary Edema; Randomized; Randomized Clinical Trials; Recommendation; Research; Risk; Safety; Sample Size; Site; Small for Gestational Age Infant; Societies; Specific qualifier value; Standardization; Stroke; Survival Analysis; Telephone; Umbilical Cord Blood; United States; Withholding Treatment; Woman; adverse outcome; adverse pregnancy outcome; authority; base; biophysical analysis; blood pressure reduction; blood pressure regulation; clinical research site; cohort; comparative effectiveness; design; experience; fetal; fetal blood; follow-up; hypertension control; neonatal death; offspring; perinatal complications; perinatal outcomes; pregnancy hypertension; pressure; public health priorities; public health relevance; randomized trial; trend; trial design; working group

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.

描述（由申请人提供）：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 是最常见的主要医学疾病，通常是轻微的（血压 <160/110 mmHg），并且与不良后果增加 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%）。尽管抗高血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) 在内的当局建议不要在怀孕期间进行降压治疗，除非高血压很严重，即 e160/110 mm Hg，因为益处不确定，而且担心治疗实际上可能会增加 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 CHTN 抗高血压治疗达到目前建议非妊娠高血压人群<140/90 mmHg 的目标，将降低包括 SGA 在内的多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）组成的联盟将确定 4700 名妊娠早期患有轻度 CHTN 且血压<155/100 mmHg（提供者更愿意不治疗）的女性，并将她们随机分配到抗高血压治疗（使用拉贝洛尔）或根据 ACOG 建议进行管理（针对更严重的 CHTN 进行抗高血压治疗）。这些妇女将接受随访，直至{产后出院和产后 3 个月（预计单独进行更长时间的随访；将考虑为临时 6 个月的电话通话提供应急资金）。将解决以下具体目标：} {1.1 主要目标：确定妊娠期轻度 CHTN 的药物治疗是否达到标准化血压}<140/90 mmHg 的目标，与标准治疗（根据 ACOG：除非高血压严重，否则不进行治疗）相比，是否可以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、严重先兆子痫、胎盘妊娠） 早剥或指示 PTB <35 周）和 2）SGA。 1.2 次要目标：为了更好地量化妊娠期间与轻度 CHTN 相关的严重孕产妇心血管结局的风险，并确定治疗的影响。二.调查患有 CHTN 的女性的最佳孕龄，以尽量减少孕产妇和围产期并发症。我们将对试验人群应用生存分析方法。三.收集和储存包括母血、脐带血和胎盘在内的生物样本，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 孕妇的效果。四.评估妊娠期间轻度 CHTN 的抗高血压治疗是否可以提高妊娠后对推荐治疗的依从性。