Impact of Low Flow Nocturnal Oxygen Therapy On Hospital Readmission/Mortalityin Patients with Heart Failure and Central Sleep Apneal (LOFT-HF)

低流量夜间氧疗对心力衰竭和中枢性睡眠呼吸暂停 (LOFT-HF) 患者再入院/死亡率的影响

• 批准号: 10005449
• 负责人: WILLIAM Tober ABRAHAM
• 金额: $ 233.19万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005449
• 关键词: Address; Adverse effects; Arousal; Biometry; Breathing; Cardiology; Central Sleep Apnea; Clinical; Clinical Trials; Collaborations; Communities; Computer software; Controlled Clinical Trials; Data; Data Coordinating Center; Disease; Double-Blind Method; EFRAC; Early Intervention; Elements; Eligibility Determination; Enrollment; Ensure; Evaluation; Event; Evidence based treatment; Failure; Goals; Guidelines; Heart; Heart failure; Home environment; Hospitalization; Hypoxemia; Infrastructure; Intervention; Lead; Leadership; Level of Evidence; Long-Term Effects; Measures; Medical; Medicine; Methods; Monitor; Moods; Morbidity - disease rate; Neuraxis; Newly Diagnosed; Outcome; Outcome Study; Oxygen; Oxygen Therapy Care; Oxyhemoglobin; Participant; Patients; Physiological; Population; Pragmatic clinical trial; Quality of life; Questionnaires; Randomized; Recurrence; Research; Research Personnel; Research Project Grants; Role; Site; Sleep; Standardization; Stress; Subgroup; Supplementation; Sympathetic Nervous System; Symptoms; Testing; Therapeutic; Time; Training; Walking; adjudication; arm; base; clinical practice; clinically relevant; cloud based; comorbidity; data management; design; exercise capacity; experience; functional status; hospital readmission; improved; inclusion criteria; innovation; mortality; novel; operation; patient oriented; pragmatic trial; preemptive intervention; primary outcome; programs; recruit; screening; secondary endpoint; service coordination; sleep quality; sound; success; time use; treatment arm; trial design; uptake; ventilation

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），在约40%的射血减少的心力衰竭患者中普遍存在 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去饱和引起。直至最近缅甸国内 CSA伴HFrEF的推荐治疗是适应性伺服通气（ASV）。最近一次多国 然而，一项试验发现ASV对死亡率有不良影响，给患者的治疗选择留下了空白 与这些共病性疾病有关虽然低流量夜间氧气，这提供了一个生理健全的 用于减弱低氧血症相关的生理应激和交感神经激活的干预，以及 改善CSA和HFrEF患者的短期中期结局，尚未有大规模研究 研究了其对临床重要结局的长期影响。我们召集了一个领导小组， 心脏病学，睡眠医学和临床试验，以进行一项务实的试验，旨在测试的假设， CSA和HFrEF患者的夜间氧疗（NOXT）将降低死亡率和计划外 因HF恶化而住院。次要终点评价发病率和死亡率的其他指标， 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2,450例家庭睡眠研究患者，估计35%（n=858）将 符合CSA的研究合格性标准。受试者将被随机分配至NOXT组或假NOXT组， 标准化评估，包括6分钟步行测试，完成验证问卷，并将 随访研究结果长达4.5年。氧气使用和氧饱和度水平将集中在 使用基于云的软件进行监控。将使用至首次事件时间分析评估主要结局， 其次是复发率。高效的数据采集和监测方法以及项目 管理层将部署。睡眠期间通气的新生理标志物将被导出以识别 响应亚组。这种严格而实用的设计将提供关键的试验数据，以确定 一种潜在有益和可接受的治疗方法的作用，尚未在大规模试验中， 发病率和死亡率高的人群，对于目前没有证据支持的疾病， 治疗睡眠评估和干预措施实际上是为了促进 他们的快速吸收和使用的心脏病学和睡眠社区。此数据协调中心应用程序 是为研究提供全面、响应迅速和创新的数据管理和研究协调 服务，生物统计分析，研究结果的严格裁定，以及集中的睡眠分析， 氧监测，以确保研究符合其里程碑。