Oxygen versus PAP for treatment of sleep apnea in chronic heart failure

氧气与 PAP 治疗慢性心力衰竭睡眠呼吸暂停的比较

• 批准号: 8441914
• 负责人: Daniel J Gottlieb
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8441914
• 关键词: Adherence; Adverse effects; Alternative Therapies; Apnea; Biological Markers; Blood Pressure; Blood Vessels; Boston; Brain natriuretic peptide; C-reactive protein; Cardiac; Cardiopulmonary; Catecholamines; Cell Adhesion Molecules; Central Sleep Apnea; Cessation of life; Characteristics; Chronic; Collagen Type III; Continuous Positive Airway Pressure; Disease; EFRAC; Echocardiography; Environmental air flow; Event; Excretory function; Exercise stress test; Future; Generations; Healthcare Systems; Heart; Heart failure; Home environment; Hospitalization; Hour; Hyperactive behavior; Hypoxemia; Hypoxia; Inflammation; Inflammatory; Interleukin-6; Isoprostanes; Lead; Left Ventricular Ejection Fraction; Lipids; Measures; Medical; Monitor; Morbidity - disease rate; Muscle Cells; Myocardial; Myocardial dysfunction; Myocardium; NF-kappa B; Obstructive Sleep Apnea; Outcome; Outcome Measure; Outcome Study; Outpatients; Oxidative Stress; Oxygen; Oxygen Consumption; Pathway interactions; Patients; Plasma; Play; Polysomnography; Prevention; Randomized; Randomized Clinical Trials; Reactive Oxygen Species; Recruitment Activity; Recurrence; Research; Risk; Role; Severities; Sleep; Sleep Apnea Syndromes; Sleep Fragmentations; Strategic Planning; Sympathetic Nervous System; Symptoms; Testing; Transplantation; Tumor Necrosis Factor-alpha; Ventricular; Ventricular Remodeling; Veterans; active method; arm; base; cytokine; design; disability; experience; functional status; health care service utilization; hypoxia inducible factor 1; improved; indexing; inflammatory marker; isoprostaglandin F2alpha type-III; lifetime risk; mortality; nocturnal Hypoxemia; pressure; primary outcome; public health relevance; respiratory; secondary outcome; standard care; transcription factor; treatment duration; treatment trial; trend; trial comparing; urinary

DESCRIPTION (provided by applicant): Chronic heart failure (HF) is a highly prevalent disease associated with high rates of mortality, which have persisted despite recent advances in pharmacologic therapy. Within the VA, outpatient encounters for HF reached 900,000 in FY09 and VA hospitalizations were over 96,000. Central sleep apnea (CSA) is a common comorbid condition, with moderate to severe CSA present in approximately one-third of patients with chronic HF with reduced ejection fraction. Central sleep apnea is associated with a doubling of mortality in chronic HF. Several small treatment trials show improvement in left ventricular ejection fraction (LVEF) following treatment of CSA with continuous positive airway pressure (CPAP) or adaptive pressure-support servo-ventilation (ASV), although the single long-term outcome study of CPAP therapy for CSA in HF found no difference in transplant-free survival despite improved LVEF. Moreover, most HF patients with CSA do not experience typical sleep apnea symptoms and are therefore often unwilling to accept the discomfort of positive airway pressure therapy. Therefore, better tolerated and possibly more effective alternatives to positive airway pressure are needed for treating CSA in patients with chronic HF. Supplemental oxygen during sleep has been shown to reduce the severity of CSA in some patients with chronic HF. Moreover, although the adverse effects of CSA on HF are likely to be multifactorial, the intermittent hypoxia characteristic of sleep apnea appears to play a central role. Hypoxia is the major cause of sympathetic hyperactivity in sleep apnea, which may contribute to progression of myocardial dysfunction through both direct effects on the myocardium and through elevation of blood pressure; it stimulates the generation of reactive oxygen species, which may contribute to myocyte damage and death; and it induces transcription factors that promote systemic inflammation. This suggests that prevention of nocturnal hypoxemia might mitigate the adverse effects of sleep apnea on the heart, even if it does not eliminate CSA per se. This study is a randomized clinical trial to assess the effects of nocturnal supplemental oxygen (NSO), CPAP and ASV for the treatment of CSA in patients with chronic HF with reduced ejection fraction. Patients with chronic HF with LVEF <45% will be screened for CSA with overnight portable sleep monitoring in their own home. A total of 161 patients with moderate to severe CSA, defined as an apnea-hypopnea index >15 with >50% of events being central apneas or hypopneas, will then be randomized in a 1:2:2:2 ratio to 3 months of treatment with optimal medical management alone, optimal medical management plus CPAP, optimal medical management plus ASV, or optimal medical management plus nocturnal supplemental oxygen. The primary outcome measures, to be made at baseline and at the end of the treatment period, will be change in LVEF as measured by echocardiogram and change in peak VO2 as measured by cardiopulmonary exercise testing. Secondary outcome measures will include 24 hour ambulatory blood pressure profile, urinary catecholamine excretion, urinary excretion of isoprostanes (a marker of oxidative stress), aminoterminal propeptide of type III collagen (a marker of ventricular remodeling), B-type natriuretic peptide, and plasma levels of several markers of inflammation. Adherence to therapy with NSO, CPAP and ASV will also be compared. The primary analysis will compare each of the active treatment groups to control. A non-inferiority design will be used to assess whether NSO and CPAP are non-inferior to ASV.

描述（由申请人提供）： 慢性心力衰竭（HF）是一种与高死亡率相关的高度普遍疾病，尽管药物治疗最近进步，但仍持续存在。在VA中，HF在09财年达到900,000的门诊遭遇，而VA住院时间超过96,000。中央睡眠呼吸暂停（CSA）是一种常见的合并症，大约三分之一的慢性HF患者中有中度至重度CSA，射血分数降低。中央睡眠呼吸暂停与慢性HF的死亡率增加一倍有关。几项小型治疗试验显示，在连续阳性气道压力（CPAP）或自适应压力支撑伺服通风（ASV）治疗CSA后，左心室射血分数（LVEF）的改善，尽管HF在HF中对CSA的单一长期结果研究均未发现，但在HF中尚未发现不受欢迎的生存差异。此外，大多数CSA患者没有经历典型的睡眠呼吸暂停症状，因此通常不愿接受阳性气道压力疗法的不适感。因此，需要更好的耐受性，并且可能需要更有效的替代气道压力来治疗慢性HF患者的CSA。已经证明睡眠过程中的补充氧气可降低某些慢性HF患者的CSA严重程度。此外，尽管CSA对HF的不利影响可能是多因素的，但睡眠呼吸暂停的间歇性缺氧特征似乎起着核心作用。缺氧是睡眠呼吸暂停中交感神经过度的主要原因，这可能会导致心肌功能障碍通过对心肌的直接影响和血压升高而导致心肌功能障碍的进展。它刺激了活性氧的产生，这可能导致肌细胞损伤和死亡。它诱导了促进全身炎症的转录因子。这表明预防夜间低氧血症可能会减轻睡眠呼吸暂停对心脏的不良影响，即使它不能消除CSA本身。 这项研究是一项随机临床试验，旨在评估夜间补充氧（NSO），CPAP和ASV对CSA治疗CSA的影响，慢性HF患者的射血分数降低。 LVEF <45％的慢性HF患者将在自己的家中进行过夜便携式睡眠监控，以筛选CSA。然后，总共161名中度至重度CSA患者定义为呼吸暂停 - 呼吸暂停指数> 15，> 50％的事件为中心呼吸暂停或呼吸症，将在1：2：2：2：2与单独使用最佳医疗管理，最佳医疗管理以及最佳医疗管理，最佳医疗管理以及最佳医疗管理以及无效的ASV和CEPTAL和CEPTAL CEPTAL和CENTERAL CEPTAL和CENTERAL CEPTAL和CENTERAL CEPTAL和CENTERAL CEPTAL和CENTERALS PLUSE CEPTAL和CEDMEN CEPTAL CELLANITAL中，以1：2：2：2的比例与3个月的治疗。根据超声心动图测量的LVEF，将在基线和治疗期结束时制定的主要结局指标将发生变化，并通过心肺运动测试测量的峰值VO2的变化。次要结局措施将包括24小时的卧床血压特征，尿尿位毒素排泄，异前列腺的尿排泄（氧化应激的标志），III型胶原蛋白的氨基抑制剂（心室重塑的标记），B-type natriutic的炎症症状和ppepty和plasmmammmame smammame smammame and smakmammame and smakmammame。还将比较使用NSO，CPAP和ASV遵守治疗。主要分析将比较每个主动治疗组以控制。非效率设计将用于评估NSO和CPAP是否不属于ASV。