PHASE II TRIAL OF SLEEP APNEA TREATMENT TO REDUCE CARDIOVASCULAR MORBIDITY

睡眠呼吸暂停治疗降低心血管发病率的二期试验

基本信息

批准号：
7941007
负责人：
Susan S. Redline
金额：
$ 219.48万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7941007
关键词：
Address Adherence Adult Adverse effects Adverse reactions Algorithms Arousal Atrial Fibrillation Biochemical Blood Pressure Blood Vessels Cardiac Cardiology Cardiovascular Diseases Cardiovascular system Caring Cell Adhesion Molecules Characteristics Clinical Congestive Heart Failure Coronary Arteriosclerosis Costs and Benefits Data Diagnosis Diagnostic Disease Dyslipidemias Electrocardiogram Evaluation Event Expenditure Frequencies Functional disorder Generations Glucose Head Health Heart Home environment Hour Hyperactive behavior Hypoxemia Hypoxia Individual Inflammatory Institution Insulin Intervention Lipids Measurement Measures Mediator of activation protein Medical Metabolic Methods Monitor Morbidity - disease rate Multicenter Studies Myocardial Ischemia NF-kappa B Obstructive Sleep Apnea Outcome Outcome Assessment Oxidative Stress Oxidative Stress Pathway Oxygen Participant Pathogenesis Pathway interactions Patient Outcomes Assessments Patients Peripheral Phase Phase II Clinical Trials Phase III Clinical Trials Physiological Polysomnography Population Predictive Value Prevention therapy Primary Care Physician Procedures Quality of life Randomized Randomized Controlled Trials Reactive Oxygen Species Recruitment Activity Regulation Research Research Infrastructure Research Personnel Risk Risk Factors Risk Reduction Role Safety Screening procedure Severities Site Sleep Sleep Apnea Syndromes Sleep Fragmentations Stress Stroke Sympathetic Nervous System Telephone Testing Therapeutic Time Titrations Visit Work abstracting airway obstruction arm arterial tonometry base cardiovascular disorder prevention cardiovascular disorder risk clinical application conventional therapy cytokine experience follow-up health related quality of life heart rate variability high risk hypoxia inducible factor 1 improved indexing inflammatory marker multidisciplinary novel novel strategies phase 2 study phase 3 study pressure programs response skills success transcription factor translational clinical trial treatment duration

项目摘要

DESCRIPTION (provided by applicant): Project Summary/Abstract This application addresses Grand Opportunity: Phase 2 Clinical Trials Program of Novel Therapies for HLB Diseases. Obstructive sleep apnea (OSA) afflicts > 5% of adults and is associated with a 2 to 4-fold increased risk of cardiovascular disease (CVD). Despite the availability of positive airway pressure (PAP) therapy, which effectively relieves airway obstruction, most OSA patients remain untreated, and thus at increased CVD risk. Suboptimal case-identification and treatment of patients with OSA is, in part, from the complexity of diagnostic algorithms and the perceived burden of using a nightly appliance, which in some individuals results in discomfort and sleep disruption. Thus, there is a need to develop and test alternative approaches to OSA treatment that address CVD risk. Emerging data indicate the central role of intermittent hypoxemia as a key mediator of pro-inflammatory, pro-oxidative and metabolic dysregulatory responses to OSA. There is thus a strong scientific basis for rigorously evaluating the efficacy of a relatively simple therapy, nocturnal supplemental oxygen (NSO), on intermediate markers of CVD risk. In this Phase 2 randomized controlled trial, we will capitalize on an existing collaborative research team (Sleep Heart Health Study investigators) experienced with the conduct of multicenter studies of OSA, expanding the team to include experienced cardiovascular translational and clinical trials investigators, to evaluate the novel use of NSO in the treatment of patients with OSA at high risk for CVD events. A pathways-directed outcomes assessment will be conducted to identify the reversibility of putative pro-inflammatory, pro-oxidative, and vascular responses to OSA. Outcomes will include critical mediators of hypoxemia effects, as well as changes in patient-reported outcomes, such as quality of life. Performing a head-to-head comparison of PAP and NSO, we will recruit 1400 patients at high risk for CVD events without significant sleepiness from 4 cardiology practice sites to undergo home sleep monitoring. We will randomize 354 of these patients with moderate to severe OSA to one of three treatment arms: a) optimized medical therapy for prevention of CVD events; b) optimized medical therapy plus PAP; or c) optimized medical therapy plus NSO. Participants will be evaluated with monthly telephone assessments and a 3-month follow-up visit, evaluating adherence, changes in OSA severity, quality of life/sleepiness, and a targeted group of intermediate CVD risk factors chosen for their predictive value for CVD and/or their sensitivity to hypoxemia. These include: 24 hour blood pressure; biochemical indices of CVD risk; sympathetic activity; and overnight indices of cardiac electrophysiologic activity. These coordinated efforts of leading institutions will accelerate the ability to conduct a large-scale Phase 3 clinical trial by assembling a multidisciplinary, multi-institutional team; establishing key study cores and infrastructure; refining recruitment, retention and measurement procedures; identifying key intermediate study endpoints; and establishing the safety and efficacy of the novel intervention (NSO) in OSA patients. (End of Abstract)

描述（由申请人提供）：项目摘要/摘要本申请涉及重大机遇：HLB 疾病新疗法的 2 期临床试验计划。超过 5% 的成年人患有阻塞性睡眠呼吸暂停 (OSA)，并且与心血管疾病 (CVD) 的风险增加 2 至 4 倍相关。尽管气道正压通气 (PAP) 治疗可有效缓解气道阻塞，但大多数 OSA 患者仍未接受治疗，因此 CVD 风险增加。 OSA 患者的病例识别和治疗效果欠佳，部分原因是诊断算法的复杂性和使用夜间器具的负担，这在某些人中会导致不适和睡眠中断。因此，需要开发和测试解决 CVD 风险的 OSA 治疗替代方法。新数据表明间歇性低氧血症作为 OSA 促炎症、促氧化和代谢失调反应的关键介质发挥着核心作用。因此，严格评估相对简单的疗法——夜间补充氧气（NSO）——对 CVD 风险中间标志物的疗效有坚实的科学依据。在这项 2 期随机对照试验中，我们将利用在 OSA 多中心研究方面经验丰富的现有合作研究团队（睡眠心脏健康研究研究者），扩大团队规模，纳入经验丰富的心血管转化和临床试验研究者，以评估NSO 在治疗 CVD 事件高危 OSA 患者中的新用途。将进行以通路为导向的结果评估，以确定对 OSA 的推定促炎症、促氧化和血管反应的可逆性。结果将包括低氧血症影响的关键介质，以及患者报告的结果的变化，例如生活质量。通过对 PAP 和 NSO 进行头对头比较，我们将从 4 个心脏病学诊所招募 1400 名 CVD 事件高风险且无明显困倦的患者进行家庭睡眠监测。我们将其中 354 名患有中度至重度 OSA 的患者随机分配至三个治疗组之一：a) 用于预防 CVD 事件的优化药物治疗； b) 优化的药物治疗加上 PAP；或 c) 优化药物治疗加上 NSO。参与者将接受每月电话评估和 3 个月的随访评估，评估依从性、OSA 严重程度的变化、生活质量/睡眠质量，以及根据其对 CVD 和/或的预测价值而选择的目标中间 CVD 风险因素组。或他们对低氧血症的敏感性。其中包括： 24 小时血压； CVD风险的生化指标；交感神经活动；和夜间心脏电生理活动指数。这些领先机构的协调努力将通过组建多学科、多机构团队来加速开展大规模3期临床试验的能力；建立关键研究核心和基础设施；完善招聘、保留和衡量程序；确定关键的中间研究终点；并确定新型干预措施 (NSO) 对 OSA 患者的安全性和有效性。（摘要完）