Impact of Low Flow Nocturnal Oxygen Therapy On Hospital Admissions and Mortality in Patients with Heart Failure and Central Sleep Apnea - DCC

低流量夜间氧疗对心力衰竭和中枢性睡眠呼吸暂停患者入院和死亡率的影响 - DCC

• 批准号: 10005453
• 负责人: Susan S. Redline
• 金额: $ 105.59万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005453
• 关键词: Address; Adherence; Adverse effects; Adverse event; Ancillary Study; Archives; Area; Arousal; Biometry; Breathing; Cardiology; Cardiovascular system; Case Report Form; Central Sleep Apnea; Clinical; Clinical Trials; Collaborations; Collection; Communication; Communities; Computer software; Custom; Data; Data Analyses; Data Collection; Data Coordinating Center; Data Files; Data Management Resources; Data Reporting; Data Set; Databases; Death Rate; Development; Disease; Documentation; Double-Blind Method; EFRAC; Eligibility Determination; Ensure; Epidemiologist; Epidemiology; Event; Evidence based treatment; Failure; Goals; Health; Heart failure; Home environment; Hospital Mortality; Hospitalization; Hospitals; Hypoxemia; Impairment; Informatics; Intervention; Leadership; Long-Term Effects; Manuals; Manuscripts; Measures; Medicine; Methods; Monitor; Moods; Morbidity - disease rate; Multicenter Studies; Neuraxis; Ohio; Online Systems; Outcome; Outcome Study; Oxygen; Oxygen Therapy Care; Oxyhemoglobin; Participant; Patient Recruitments; Patients; Phase; Physicians; Physiological; Polysomnography; Population; Preparation; Procedures; Process; Protocols documentation; Publications; Quality Control; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Reading; Recurrence; Reporting; Research; Research Design; Research Training; Resolution; Resources; Role; Safety; Secure; Services; Site; Sleep; Source; Standardization; Statistical Data Interpretation; Stress; Subgroup; Summary Reports; Supplementation; Support System; Sympathetic Nervous System; System; Testing; Therapeutic; Time; Training; United States National Institutes of Health; Universities; Validation; Walking; Woman; Work; Writing; adjudicate; adjudication; base; clinical practice; cloud based; comorbidity; data dissemination; data management; data quality; data sharing; design; distributed data; diverse data; electronic data capture system; exercise capacity; experience; functional status; heart function; improved; individualized medicine; innovation; member; mortality; novel; participant retention; pragmatic trial; primary outcome; programs; quality assurance; response; secondary endpoint; secondary outcome; service coordination; signal processing; sleep quality; sound; treatment adherence; trial design; uptake; ventilation; web site; web-accessible

Central sleep apnea (CSA), prevalent in approximately 40% of patients with heart failure with reduced ejection fraction (HFrEF), predicts high rates of morbidity, hospitalizations, and mortality. Adverse effects are thought to be attributable to hypoxemia, central nervous system arousal, and sympathetic nervous system activation resulting from episodic breathing disturbances and oxyhemoglobin desaturation. Until recently, the recommended treatment for CSA with HFrEF was adaptive servo-ventilation (ASV). A recent multi-national trial, however, identified an adverse effect of ASV on mortality, leaving a void in therapeutic options for patients with these co-morbid disorders. Although low flow nocturnal oxygen, which provides a physiologically sound intervention for blunting hypoxemia-associated physiological stresses and sympathetic activation, and improves short-term intermediate outcomes in patients with CSA and HFrEF, no large scale study yet has examined its long term impact on clinically important outcomes. We have assembled a team of leaders in cardiology, sleep medicine and clinical trials to conduct a pragmatic trial designed to test the hypothesis that nocturnal oxygen therapy (NOXT) in patients with CSA and HFrEF will reduce mortality and unplanned hospitalizations for worsening HF. Secondary endpoints evaluate other measures of morbidity and mortality, functional status, exercise capacity, quality of life, mood, and sleep quality. Using a double-blinded, randomized design, we will screen 2,450 patients with home sleep studies, estimating that 35% (n=858) will meet study eligibility criteria for CSA. Participants will be randomized to NOXT or sham-NOXT and undergo standardized assessments including a 6 minute walk test, complete validated questionnaires, and will be followed for study outcomes for as long as 4.5 years. Oxygen use and oxygen saturation levels will be centrally monitored using cloud-based software. Primary outcomes will be assessed using a time to first event analysis, and secondarily as recurrent event rates. Highly efficient methods for data capture and monitoring and project management will be deployed. Novel physiological markers of ventilation during sleep will be derived to identify responsive subgroups. This rigorous yet practical design will provide pivotal trial data needed to identify the role of a potentially beneficial and acceptable therapy which has yet to be tested on a large scale in a population with high morbidity and mortality, for a condition where there is no current evidence-based treatment. The sleep assessments and interventions are practically designed with the objective of facilitating their rapid uptake and use by the cardiology and sleep communities. This Data Coordinating Center application is to provide the study comprehensive, responsive, and innovative data management and study coordination services, biostatistical analysis, rigorous adjudication of study outcomes, and centralized sleep analysis and oxygen monitoring to ensure that the study meets its milestones.

中枢性睡眠呼吸暂停 (CSA) 常见于约 40% 射血减少的心力衰竭患者 分数（HFrEF），预测高发病率、住院率和死亡率。不利影响被认为是 可归因于低氧血症、中枢神经系统觉醒和交感神经系统激活 由阵发性呼吸障碍和氧合血红蛋白饱和度降低引起。直到最近， 对于伴有 HFrEF 的 CSA，推荐的治疗方法是适应性伺服通气 (ASV)。最近的一项多国试验 然而，确定了 ASV 对死亡率的不利影响，导致患有以下疾病的患者缺乏治疗选择： 这些共病。虽然夜间氧气流量低，但提供了生理上的健康 干预减弱低氧血症相关的生理应激和交感神经激活，并改善 CSA 和 HFrEF 患者的短期中期结果，尚未有大规模研究检验其 对临床重要结果的长期影响。我们组建了一支由心脏病学、睡眠学领域的领导者组成的团队 医学和临床试验进行实用试验，旨在检验夜间氧气的假设 CSA 和 HFrEF 患者的治疗 (NOXT) 将降低死亡率和计划外住院治疗 心力衰竭恶化。次要终点评估发病率和死亡率、功能状态、 运动能力、生活质量、情绪和睡眠质量。使用双盲、随机设计，我们将 通过家庭睡眠研究对 2,450 名患者进行筛查，估计 35% (n=858) 符合研究资格标准 国家安全局。参与者将被随机分配到 NOXT 或假 NOXT 组并接受标准化评估，包括 6 分钟步行测试，完成经过验证的问卷，并将跟踪研究结果 4.5年。氧气使用量和氧饱和度水平将使用基于云的软件进行集中监控。 主要结果将使用首次事件发生时间分析进行评估，其次评估复发事件发生率。 将部署高效的数据采集、监控和项目管理方法。小说 将得出睡眠期间通气的生理标志物，以识别反应亚组。这严格的 然而，实际设计将提供关键的试验数据，以确定潜在有益和有效的作用所需的关键试验数据。 可接受的疗法尚未在高发病率人群中进行大规模测试 死亡率，目前没有基于证据的治疗方法。睡眠评估和 干预措施的实际设计目的是促进心脏病学快速吸收和使用 和睡眠社区。该数据协调中心应用程序旨在提供全面的研究， 反应灵敏、创新的数据管理和研究协调服务、生物统计分析、严格的 研究结果的裁决，以及集中的睡眠分析和氧气监测，以确保研究 达到其里程碑。