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: 9751958
• 负责人: Susan S. Redline
• 金额: $ 110.32万
• 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 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751958
• 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 Quality; Data Reporting; Data Set; Databases; Death Rate; Development; Disease; Documentation; Double-Blind Method; EFRAC; Eligibility Determination; Ensure; Environmental air flow; 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; data management; data sharing; design; distributed 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; 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)，在射血减少的心力衰竭患者中约40%普遍存在 分数(HFrEF)预测高发病率、住院率和死亡率。不良影响被认为是 可归因于低氧血症、中枢神经系统唤醒和交感神经系统激活 由间歇性呼吸紊乱和氧合血红蛋白降低引起。直到最近， 对于CSA合并HFrEF，推荐的治疗方法是自适应伺服呼吸机(ASV)。最近的一次多国试验， 然而，发现ASV对死亡率的不利影响，为患有ASV的患者的治疗选择留下了空白 这些并存的疾病。虽然夜间低流量的氧气提供了生理上的声音 干预钝化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，目前还没有大规模研究检查其 对临床重要结果的长期影响。我们组建了一支由心脏病、睡眠等领域的领军人物组成的团队 医学和临床试验进行务实的试验，旨在检验夜间氧气 CsA和HFrEF患者的治疗(NOXT)将减少死亡率和计划外住院 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 筛选有家庭睡眠研究的2450名患者，估计35%(n=858)将满足以下研究资格标准 CsA。参与者将被随机分配到NOXT或Sham-NOXT，并接受标准化评估，包括 6分钟步行测试，完整的有效问卷，并将跟踪研究结果长达 四年半。氧气使用和血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，其次是复发事件发生率。 将部署高效的数据采集和监测方法以及项目管理。小说 将得出睡眠期间通风的生理标记，以识别反应亚组。这份严谨 然而，实际设计将提供所需的关键试验数据，以确定潜在有益和 可接受的治疗方法，尚未在发病率较高的人群中进行大规模测试， 死亡率，对于目前没有循证治疗的情况。睡眠评估和 干预措施的设计实际上是为了促进心脏科对它们的快速吸收和使用 和睡眠社区。本数据协调中心的应用是为了提供全面的研究， 响应迅速、创新的数据管理和研究协调服务、生物统计分析、严谨 研究结果的判定，以及集中的睡眠分析和氧气监测，以确保研究 达到它的里程碑。