A Planning Study: Sleep Apnea Intervention for Cardiovascular Disease Reduction

规划研究：睡眠呼吸暂停干预减少心血管疾病

• 批准号: 8015486
• 负责人: MURRAY A MITTLEMAN
• 金额: $ 91.02万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015486
• 关键词: Accounting; Acute; Address; Adherence; Adult; Adverse effects; Adverse reactions; Atrial Fibrillation; Behavior; Behavior Therapy; Behavioral; Biochemical; Biological Assay; Blood Pressure; Breathing; Cardiac; Cardiology; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Characteristics; Choices and Control; Clinic; Clinical; Clinical Trials; Control Groups; Coronary Arteriosclerosis; Data; Data Collection; Devices; Dilator; Disease; Disease Pathway; Dose; Dyslipidemias; Echocardiography; Education; Educational Status; Effectiveness; Enrollment; Evaluation; Foundations; Functional disorder; Future; Genetic Crossing Over; Glucose; Health; Heart failure; High Prevalence; Hour; Hygiene; Hyperactive behavior; Hypertension; Hypoxemia; Impairment; Inflammation; Inflammatory; Insulin Resistance; Intervention; Intervention Studies; Kidney; Left Ventricular Hypertrophy; Level of Evidence; Masks; Measurement; Measures; Medical; Medicine; Metabolic Control; Monitor; Moods; Morbidity - disease rate; Morphology; Nose; Obstructive Sleep Apnea; Outcome; Outcome Measure; Outcome Study; Oxidative Stress Pathway; Participant; Pathogenesis; Pathway interactions; Patient Outcomes Assessments; Patients; Pattern; Phase; Phase III Clinical Trials; Physicians; Physiological; Placebo Effect; Population; Procedures; Protocols documentation; Psychologist; Pulmonary artery structure; Quality of life; Randomized; Randomized Controlled Trials; Recommendation; Recruitment Activity; Recurrence; Relative (related person); Research Design; Research Personnel; Risk; Risk Factors; Role; Running; Safety; Sampling; Secondary Prevention; Serious Adverse Event; Severities; Site; Sleep; Sleep Apnea Syndromes; Sleep Deprivation; Sleep Disorders; Staging; Stress; Stroke; Structure; Subgroup; Subjects Selections; Sympathetic Nervous System; Telephone; Testing; Thrombosis; Time; Treatment Protocols; Uncertainty; Visit; abstracting; arm; arterial stiffness; arterial tonometry; base; cardiovascular disorder prevention; cardiovascular disorder risk; clinical practice; design; diaries; disease characteristic; effective therapy; follow-up; group intervention; health related quality of life; improved; indexing; inflammatory marker; interest; lipid metabolism; mortality; patient population; pressure; prospective; respiratory; response; social cognitive theory; treatment adherence

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) afflicts > 5% of adults and is associated with a 2 to 4-fold increased risk of cardiovascular disease (CVD). Small, short term studies have provided preliminary evidence that treatment of OSA with positive airway pressure (PAP) improves CVD risk factors. Given the high prevalence of OSA and its profound physiological disturbances, effective treatment could be expected to significantly reduce CVD burden in these patients. However, the role of PAP for primary or secondary prevention of CVD is unclear due to both concerns about long-term PAP adherence and the relative absence of rigorously designed large-scale prospective clinical trials evaluating the impact of OSA treatment on clinical endpoints. We have assembled a multi-disciplinary investigator team to address the critical study design issues relevant for launching a later large-scale Phase 3 randomized controlled trial (RCT). In this planning study, we propose to conduct a Phase 2 RCT which includes evaluation of alternative study design features such as the choice of control arms, approaches for optimizing PAP adherence, and choice of study endpoints. We aim to recruit patients with moderate to severe OSA and with CVD risk factors or established CVD from a network of large, regional sleep disorders centers. After a 2-week run-in period, 180 participants will be randomized to one of 3 intervention arms: an active PAP treatment arm or one of two control arms (sham-CPAP vs. conservative medical therapy, CMT). The use of two control arms will allow assessment of the trade-offs of using alternative control interventions that pose different levels of burden and allow different degrees of blinding. Alternative approaches for enhancing adherence to PAP, one of which includes an augmented behavioral-based intervention, also will be evaluated through a second-stage randomization procedure. All participants will undergo a standardized assessment of CVD risk factors at baseline and at 12 months, including measurement of 24 hour blood pressure, arterial tonometry, cardiac echocardiography, bioassays for markers in CVD pathogenesis pathways, and patient-reported outcomes. Interim monitoring for safety and adherence will be performed every two months. Analyses will: 1) quantify the retention and adherence rates, recruitment yields, and safety parameters within each study arm; 2) compare changes in the primary clinical outcome, average systolic blood pressure, across arms; 3) estimate effect sizes for changes in other intermediate markers and patient-reported outcomes; and 4) explore subgroup differences in responses. The proposed data collection, including a rigorous evaluation of safety indicators, alternative design features, and intermediate markers, will lay the foundation for a later large-scale study that will be designed, for the first time, to provide Level I evidence that addresses the effectiveness of OSA treatment for reducing CVD morbidity and mortality. (End of Abstract)

描述(由申请人提供)： 阻塞性睡眠呼吸暂停(OSA)困扰着5%的成年人，并与心血管疾病(CVD)风险增加2-4倍有关。小规模、短期的研究已经提供了初步证据，表明阻塞性睡眠呼吸暂停综合征(OSA)的气道正压(PAP)治疗可以改善心血管疾病的危险因素。鉴于OSA的高患病率及其深刻的生理障碍，有效的治疗有望显著减轻这些患者的心血管负担。然而，由于对PAP长期依从性的担忧，以及相对缺乏评估OSA治疗对临床终点的影响的严格设计的大型前瞻性临床试验，PAP在心血管疾病一级或二级预防中的作用尚不清楚。我们已经组建了一个多学科的研究团队，以解决与启动后来的大规模第三阶段随机对照试验(RCT)相关的关键研究设计问题。在这项规划研究中，我们建议进行第二阶段随机对照试验，其中包括对替代研究设计特征的评估，如控制臂的选择、优化PAP依从性的方法以及研究终点的选择。我们的目标是从一个大型地区性睡眠障碍中心网络招募中重度OSA和有CVD危险因素或已有CVD的患者。在为期两周的磨合期后，180名参与者将被随机分配到3个干预组中的一个：主动PAP治疗组或两个对照组中的一个(假CPAP与保守药物治疗，CMT)。使用两个控制臂将能够评估使用替代控制干预措施的权衡，这些干预措施造成不同程度的负担并造成不同程度的致盲。提高对PAP依从性的替代方法，其中之一包括基于行为的强化干预，也将通过第二阶段随机程序进行评估。所有参与者都将在基线和12个月时接受心血管危险因素的标准化评估，包括24小时血压测量、动脉血压测量、心脏超声心动图、心血管疾病发病途径标志物的生物分析以及患者报告的结果。将每两个月进行一次安全和遵守情况的临时监测。分析将：1)量化每个研究组内的保留率和依从率、招募收益率和安全参数；2)比较主要临床结果、跨组平均收缩压的变化；3)估计其他中间标记物和患者报告结果变化的影响大小；以及4)探索反应中的亚组差异。拟议的数据收集，包括对安全指标、替代设计特征和中间标记的严格评估，将为以后的大规模研究奠定基础，该研究将首次设计为提供I级证据，说明OSA治疗在降低心血管疾病发病率和死亡率方面的有效性。 (摘要结束)