PROtecting Maternal brains from Injury and Stroke (PROMIS): a Single-center Phase 2 Clinical Trial

保护母亲大脑免受损伤和中风 (PROMIS)：单中心 2 期临床试验

• 批准号: 10575711
• 负责人: Eliza C Miller
• 金额: $ 24.68万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-03-02 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10575711
• 关键词: Accounting; Acute; Acute Brain Injuries; Address; Admission activity; Affect; Algorithms; Antihypertensive Agents; Blood Pressure; Blurred vision; Brain; Brain Injuries; Caliber; Cerebral Edema; Cerebral hemisphere hemorrhage; Cerebrovascular Circulation; Cerebrovascular Spasm; Cerebrum; Clinical; Clinical Research; Data; Discipline of obstetrics; Ensure; Feasibility Studies; Functional disorder; Funding; Goals; Guidelines; Headache; Hemorrhage; Homeostasis; Hospitalization; Hour; Hypertension; Impairment; Individual; Injury; Intensive Care Units; Intervention; Intracranial Hypertension; Intravenous; Ischemia; Ischemic Stroke; Life; Magnesium; Maternal Mortality; Measures; Methods; Modality; Monitor; Near-Infrared Spectroscopy; Nervous System Trauma; Neurologic; Neurologic Symptoms; Outcome; Pain; Patients; Perfusion; Phase; Phase II Clinical Trials; Postpartum Period; Pre-Eclampsia; Pregnancy; Proxy; Recommendation; Risk; Risk Reduction; Stroke; System; TBI Patients; Testing; Time; United States National Institutes of Health; Women' s Health; adverse maternal outcomes; adverse pregnancy outcome; antenatal; arteriole; blood pressure control; brain tissue; cerebral hypoperfusion; cerebrovascular; clinical care; disability; experience; high reward; high risk; improved; indexing; novel; novel strategies; people of color; personalized approach; portability; postpartum complications; pregnancy disorder; pregnant; pressure; prevent; randomized, clinical trials; response; severe maternal morbidity; tissue oxygenation

PROJECT SUMMARY/ABSTRACT Preeclampsia (PEC) affects 1 in 20 pregnancies and is a leading cause of severe maternal morbidity and mortality. Life-threatening neurological complications of PEC include intracerebral hemorrhage, cerebral edema, cerebral vasospasm, and ischemic stroke. Most maternal deaths due to PEC-associated cerebrovascular complications occur postpartum. Despite this, clinical research has primarily focused on antepartum blood pressure (BP) treatment, rather than postpartum. Current BP management guidelines for postpartum patients recommend absolute thresholds for treatment, without accounting for factors such as degree or rapidity of change from patients’ baseline BP. Clinicians urgently need better methods to 1) identify individuals at risk for these devastating postpartum complications, and 2) guide BP management using personalized, precise targets optimized for brain protection. Normal brain function requires constant cerebral blood flow (CBF). Cerebral arterioles respond actively in response to fluctuations in BP, protecting the brain from acute injury due to hypo- or hyper-perfusion, a phenomenon known as cerebral autoregulation. Changes in cerebral autoregulation contribute to the pathophysiology of postpartum cerebrovascular complications. In individuals with impaired autoregulation, targeting BP parameters to optimize cerebral perfusion could help reduce the risk of ischemia, elevated intracranial pressure, cerebral edema and intracerebral hemorrhage. Near-infrared spectroscopy (NIRS) is a non-invasive bedside monitoring modality that measures brain tissue oxygenation as a proxy for CBF. The use of NIRS-based autoregulation-guided BP targets improves clinical outcomes in neurologically injured patients. We propose to apply this novel approach to the management of postpartum PEC (within 6 weeks of delivery) in a single-center, Phase II clinical trial, PROMIS (PROtecting Maternal brains from Injury and Stroke). We will use NIRS monitoring to calculate personalized limits of cerebral autoregulation in 20 individuals with postpartum preeclampsia with severe features (Aim 1); and pilot the use of autoregulation-guided BP goals for postpartum preeclampsia with severe features in an additional 20 individuals (Aim 2). We hypothesize that: 1) standard guideline-based BP management for postpartum PEC over 24 hours will result in ≥ 10% of time during which BP exceeds personalized upper or lower limits of autoregulation; 2) more time with BP outside personalized limits of autoregulation will be associated with a) increased neurological symptoms and b) objective evidence of cerebral hypo- or hyper-perfusion by NIRS; and 3) targeted BP management using autoregulation-guided goals will result in fewer neurological symptoms and less time spent outside limits of autoregulation, compared with patients treated according to current guidelines. This novel, high-risk, high-reward trial will be the first early phase interventional neuro-obstetric trial aimed at preventing postpartum maternal death and disability due to neurological causes.

项目概要/摘要 先兆子痫 (PEC) 影响二十分之一的妊娠，是严重孕产妇发病和 PEC 危及生命的神经系统并发症包括脑出血、脑出血。 水肿、脑血管痉挛和缺血性中风大多数孕产妇死亡是由 PEC 相关引起的。 尽管如此，脑血管并发症还是发生在产后。 产前血压（BP）治疗，而不是当前的产后血压管理指南。 产后患者建议治疗的绝对阈值，而不考虑以下因素 临床医生迫切​​需要更好的方法来 1) 识别患者基线血压的变化程度或速度。 面临这些毁灭性产后并发症风险的个人，以及 2) 指导血压管理 针对大脑保护而优化的个性化、精确目标 正常的大脑功能需要持续的大脑保护。 脑动脉对血压波动做出积极反应，保护大脑。 由于灌注不足或过度造成的急性损伤，这种现象称为脑自动调节变化。 脑自动调节有助于产后脑血管并发症的病理生理学。 对于自动调节受损的个体，针对血压参数来优化脑灌注可能会有所帮助 降低缺血、颅内压升高、脑水肿和脑出血的风险。 近红外光谱 (NIRS) 是一种测量脑组织的非侵入性床边监测方式 使用基于 NIRS 的自动调节引导血压目标可改善临床情况。 我们建议将这种新方法应用于神经损伤患者的治疗。 单中心 II 期临床试验 PROMIS（PROtecting 受伤和中风的母亲大脑）我们将使用 NIRS 监测来计算个性化的限制。 20 名具有严重特征的产后先兆子痫个体的脑自动调节（目标 1）； 在另一项研究中，使用自动调节引导的血压目标来治疗具有严重特征的产后先兆子痫 20 人（目标 2）：1）基于标准指南的产后 PEC 血压管理。 超过24小时将导致≥10%的时间血压超过个性化上限或下限 自我调节；2) 在个人化的自我调节限制之外的更多时间与以下因素相关： 神经系统症状增加，b) 近红外光谱（NIRS）显示脑灌注不足或过度的客观证据； 3) 使用自动调节指导目标进行有针对性的血压管理将减少神经系统症状和 与根据现行指南治疗的患者相比，在自动调节范围之外花费的时间更少。 这项新颖、高风险、高回报的试验将是第一个早期阶段介入神经产科试验，旨在 预防产后因神经原因导致的孕产妇死亡和残疾。