Treatment of Sleep-Disordered Breathing With Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- ResMed
- 入组人数
- 1,325
- 试验地点
- 531
- 主要终点
- All Cause Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure
研究概览
简要总结
The purpose of this trial is to evaluate the long-term effects and cost-effectiveness of adaptive servo-ventilation (ASV) on the mortality and morbidity of patients with stable heart failure due to left ventricular systolic dysfunction, already receiving optimal medical therapy, who have sleep disordered breathing (SDB) that is predominantly central sleep apnea. Assumptions: the intervention reduces the hazard rate by 20%. The event rate in the control group is 35% in the first year. It is assumed that the hazard rate is constant over time.
详细描述
Objective: The purpose of this trial is to evaluate the long-term effects and cost-effectiveness of adaptive servo-ventilation (ASV) on the mortality and morbidity of patients with stable heart failure due to left ventricular systolic dysfunction, already receiving optimal medical therapy, who have sleep disordered breathing (SDB) that is predominantly central sleep apnea.
Study Design: Randomized, multicentre, international trial with parallel group design, with patients randomized to either control (optimal medical management) or active treatment (optimal medical treatment plus use of adaptive servoventilation) in a 1:1 ratio. There will be no sham-positive airway pressure treatment in the control arm. Assumptions: the intervention reduces the hazard rate by 20%. The event rate in the control group is 35% in the first year. It is assumed that the hazard rate is constant over time. The trial is an event driven design: the final analysis is to be performed latest when 651 events have been observed. The primary analysis is in the intention-to-treat population that consists of all patients randomized.
Number of Patients: 1116 patients will be randomly assigned to one of the two treatment groups. A 20% drop out rate is estimated.
Selection criteria: Patients at the age of or over 22 years with severe chronic heart failure (chronic HF), New York Heart Association (NYHA) class III-IV or NYHA class II with at least one hospitalization for HF within the last 24 months, with Left Ventricular Ejection Fraction (LVEF) less or equal 45% by means of echocardiography, radionuclide ventriculography or cardiac MRI and Sleep Disordered Breathing (SDB) (apnoea-hypopnoea-index (AHI > 15/h) with 50% central events and a central AHI ≥ 10/h, no change of medication and no hospitalization for more than 1 month before randomization and medical therapy according to the applicable guidelines (European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) respectively).
Primary Endpoints: Time to first event of:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 22 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be at least 22 years old
- •Chronic heart failure (at least 12 weeks since diagnosis) according to the current applicable guidelines (ESC, ACC/AHA)
- •Left ventricular systolic dysfunction (LVEF ≤45% by imaging method such as echocardiography, radionuclide angiography, left ventriculography, or cardiac magnetic resonance imaging) documented less than 12 weeks before randomisation
- •NYHA class III or IV at the time of inclusion or NYHA class II with at least one hospitalisation for HF in the last 24 months
- •No hospitalisation for heart failure for at least 4 weeks prior to inclusion
- •Optimised medical treatment according to applicable guidelines with no new class of disease modifying drug for more than 4 weeks prior to randomisation. In case of no beta blockers or ACE (angiotensin converting Enzyme) inhibitors/ ARB (angiotensin receptor blocker) antagonists the reasons must be documented
- •SDB (AHI > 15/h with ≥ 50% central events and a central AHI ≥ 10/h, derived from polygraphy or polysomnography (based on total recording time (TRT)), documented less than 4 weeks before randomisation. Flow measurement has to be performed with nasal cannula
- •Patients for whom the use of AutoSet CS2 (TM)/VPAP Adapt may be contra-indicated because of symptomatic hypotension or significant intravascular volume depletion or pneumothorax or pneumomediastinum
- •Patient is able to fully understand study information and signed informed consent
排除标准
- •Significant COPD (chronic obstructive pulmonary disease) with Forced Expiratory Volume within one second (FEV1) <50% (European Respiratory Society criteria) in the last four weeks before randomisation
- •Oxygen saturation at rest during the day ≤ 90% at inclusion
- •Current use of Positive Airway Pressure (PAP) - therapy
- •Life expectancy < 1 year for diseases unrelated to chronic HF
- •Cardiac surgery, Percutaneous coronary intervention (PCI), Myocardial Infarction (MI) or unstable angina within 6 months prior to randomisation
- •CRT (cardiac resynchronisation therapy)-implantation or ICD-implantation scheduled or within 6 months prior to randomisation
- •Transient ischemic attack (TIA) or Stroke within 3 months prior to randomisation
- •Primary hemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant, or any valvular disease expected to lead to surgery during the trial
- •Acute myocarditis/pericarditis within 6 months prior to randomisation
- •Untreated or therapy refractory Restless legs-Syndrome (RLS) according to criteria listed in Appendix IX at the time of study entry
- •Pregnancy
结局指标
主要结局
All Cause Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure
时间窗: time to first event, assessed for up to 70 weeks
Cardiovascular Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure
时间窗: time to first event, assessed for up to 70 weeks
All Cause Mortality or All Cause Unplanned Hospitalisation/Prolongation of Hospitalisation
时间窗: time to first event, assessed for up to 70 weeks
次要结局
- Death From Any Cause(the last follow up or at the last available observation within Follow Up (FU), assessed for up to 70 weeks)
- First Survived Resuscitation of Sudden Cardiac Arrest (Evaluation Will Also be Made by the ERC)(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Age Baseline(1 x at Baseline)
- Creatinine Baseline(1 x at baseline)
- 6-Min Walk Distance(1 x at baseline)
- Epworth Sleepiness Scale (ESS)(1 x at baseline)
- Unplanned Hospitalisation/Prolongation of Hospitalisation Due to Worsening of Heart Failure(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Cardiovascular Death(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- First Survived Resuscitation for Any Reason (Evaluation Will Also be Made by the ERC)(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Blood Pressure Diastolic Baseline(1 x at baseline)
- Hemoglobine Baseline(1 x at baseline)
- Glomerular Filtration Rate Baseline(1 x at baseline)
- Adequate Shock in Patients With ICD (Evaluation of Appropriateness Will Also be Made by the Endpoint Review Committee, ERC), Long-Term Atrial Defibrillator Insertion or Cardiovascular Death(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Body Mass Index (BMI) Baseline(1 x baseline)
- Apnoea-Hypopnea-Index (AHI) at Baseline(1 x at baseline)
- Central Apnoea Index/Total AHI(1 x at baseline)
- Changes in NYHA Classification as Compared to Baseline(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Non-cardiovascular Death(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Unplanned Hospitalisation/Prolongation of Hospitalisation for Other Reasons or Death(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Left Ventricular Ejection Fraction at Baseline(1x at baseline)
- Oxygen Desaturation Index (ODI) at Baseline(1 x at baseline)
- Time Until Unplanned Hospitalisation/Prolongation of Hospitalisation for Cardiovascular Cause or Cardiovascular Death/ Time Frame(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Percent of Follow up Days Which Patient Survives and is Not Hospitalized/Hospital Stay is Not Prolonged for Cardiovascular Cause(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Changes in QoL (Minnesota) as Compared to Baseline(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Atrial Fibrillation at Follow-up Visits(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Body Weight Baseline(1 x at baseline)
- Blood Pressure Systolic Baseline(1 x at baseline)
- Central AHI/Total AHI at Baseline(1 x at baseline)
- Changes of AHI and Oxygen Desaturation Index Compared to Baseline(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Oxygen Saturation Baseline(1 x at baseline)
- Time With Oxygen Saturation Below 90%(1 x at baseline)
- Changes in Six Minute Walking Distance (6MWD) as Compared to Baseline(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- AHI Below 10 Per Hour at Twelve Months and ODI Below 5 Per Hour at Twelve Months(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Number and Cost of Hospitalisations (With Tariff/DRG, Diagnoses and Procedures for Calculating DRG or Length of Stay and Level of Care Provided)(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Difference in Utilities / QoL (Minnesota and EQ5D) Compared to Control Arm(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Difference in Cost of Resources Consumed(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Changes in Renal Function (Based on Serum Creatinine) as Compared to Baseline(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Incremental Cost-efficacy Ratio(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)
- Incremental Cost-utility Ratio(the last follow up or at the last available observation within FU, assessed for up to 70 weeks)