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.

项目总结/摘要 先兆子痫（PEC）影响20例妊娠中的1例，是严重孕产妇发病的主要原因， mortality. PEC的危及生命的神经系统并发症包括脑内出血、脑出血、脑出血和脑出血。 水肿、脑血管痉挛和缺血性中风。大多数产妇死亡是由于与PEC有关的 产后出现脑血管并发症。尽管如此，临床研究主要集中在 产前血压（BP）治疗，而不是产后。现行BP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， 患者基线BP变化的程度或速度。临床医生迫切需要更好的方法来1）识别 个人在这些毁灭性的产后并发症的风险，和2）指导BP管理使用 针对大脑保护进行了优化的个性化精确目标。正常的大脑功能需要持续的 血流量（CBF）。大脑小动脉对血压波动做出积极反应，保护大脑 由于低灌注或高灌注引起的急性损伤，这种现象称为脑自动调节。变化 在脑自动调节中的作用有助于产后脑血管并发症的病理生理学。在 自动调节受损的个体，针对BP参数优化脑灌注可能有助于 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）是一种非侵入性床边监测模式，可测量脑组织 氧合作为CBF的代表。使用基于NIRS的自动调节引导BP目标可改善临床 神经损伤患者的预后。我们建议将这种新的方法应用于管理 产后PEC（分娩后6周内）在单中心、II期临床试验PROMIS（PROtecting 损伤和中风的母体脑）。我们将使用近红外光谱监测来计算个性化的限制， 20例重度产后先兆子痫患者的脑自动调节（目的1）; 在一个额外的研究中， 20人（目标2）。我们假设：1）产后PEC的标准指南为基础的血压管理 超过24小时将导致≥ 10%的时间内BP超过个性化的上限或下限， 自动调节; 2）BP超出自动调节的个性化限制的更多时间将与a） 增加的神经症状和B）通过NIRS得到的脑低灌注或高灌注的客观证据;和 3)使用自我调节指导的目标进行有针对性的BP管理将导致更少的神经症状， 与根据当前指南治疗的患者相比，在自动调节限度之外花费的时间更少。 这项新的、高风险、高回报的试验将是第一个早期干预性神经产科试验， 预防产后产妇因神经系统原因死亡和残疾。