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N/A N=1,325 Randomized Treatment

Treatment of Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure

Heart Failure · Sleep Disordered Breathing

Enrolled (actual)
1,325
Serious AEs
71.5%
Results posted
May 2020
Primary outcome: Primary: All Cause Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure — 360; 335 Participants

Study Design & Population

Study type
Interventional
Phase
N/A
Interventions
Europe: AutoSet CS (USA: VPAP Adapt SV) (Device)
Age
Adult, Older Adult · 22+ yrs
Sex
All
Sponsor
ResMed
Primary completion
Apr 2015

Outcome Measures

OutcomeResultp-value
PRIMARY
All Cause Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure
360; 335
PRIMARY
Cardiovascular Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure
345; 317
PRIMARY
All Cause Mortality or All Cause Unplanned Hospitalisation/Prolongation of Hospitalisation
482; 465
SECONDARY
Death From Any Cause
232; 193
SECONDARY
Non-cardiovascular Death
33; 35
SECONDARY
Cardiovascular Death
199; 158
SECONDARY
Unplanned Hospitalisation/Prolongation of Hospitalisation Due to Worsening of Heart Failure
287; 272
SECONDARY
Unplanned Hospitalisation/Prolongation of Hospitalisation for Other Reasons or Death
452; 448
SECONDARY
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
45; 65
SECONDARY
First Survived Resuscitation for Any Reason (Evaluation Will Also be Made by the ERC)
25; 19
SECONDARY
First Survived Resuscitation of Sudden Cardiac Arrest (Evaluation Will Also be Made by the ERC)
18; 16
SECONDARY
Age Baseline
69.6; 69.3
SECONDARY
Body Weight Baseline
85.6; 86.1
SECONDARY
Body Mass Index (BMI) Baseline
28.4; 28.6
SECONDARY
Left Ventricular Ejection Fraction at Baseline
32.2; 32.5
SECONDARY
Blood Pressure Systolic Baseline
122.3; 122.1
SECONDARY
Blood Pressure Diastolic Baseline
73.7; 73.3
SECONDARY
Hemoglobine Baseline
13.8; 13.9
SECONDARY
Creatinine Baseline
1.4; 1.4
SECONDARY
Glomerular Filtration Rate Baseline
57.8; 59.3
SECONDARY
6-Min Walk Distance
334.0; 337.9
SECONDARY
Epworth Sleepiness Scale (ESS)
7.0; 7.1
SECONDARY
Apnoea-Hypopnea-Index (AHI) at Baseline
31.2; 31.7
SECONDARY
Central Apnoea Index/Total AHI
44.6; 46.5
SECONDARY
Central AHI/Total AHI at Baseline
80.8; 81.8
SECONDARY
Oxygen Desaturation Index (ODI) at Baseline
32.1; 32.8
SECONDARY
Oxygen Saturation Baseline
92.8; 92.8
SECONDARY
Time With Oxygen Saturation Below 90%
50.5; 55.7
SECONDARY
Time Until Unplanned Hospitalisation/Prolongation of Hospitalisation for Cardiovascular Cause or Cardiovascular Death/ Time Frame
SECONDARY
Percent of Follow up Days Which Patient Survives and is Not Hospitalized/Hospital Stay is Not Prolonged for Cardiovascular Cause
SECONDARY
Changes in NYHA Classification as Compared to Baseline
SECONDARY
Changes in QoL (Minnesota) as Compared to Baseline
SECONDARY
Changes in Renal Function (Based on Serum Creatinine) as Compared to Baseline
SECONDARY
Changes in Six Minute Walking Distance (6MWD) as Compared to Baseline
SECONDARY
Changes of AHI and Oxygen Desaturation Index Compared to Baseline
SECONDARY
AHI Below 10 Per Hour at Twelve Months and ODI Below 5 Per Hour at Twelve Months
SECONDARY
Atrial Fibrillation at Follow-up Visits
SECONDARY
Number and Cost of Hospitalisations (With Tariff/DRG, Diagnoses and Procedures for Calculating DRG or Length of Stay and Level of Care Provided)
SECONDARY
Difference in Utilities / QoL (Minnesota and EQ5D) Compared to Control Arm
SECONDARY
Difference in Cost of Resources Consumed
SECONDARY
Incremental Cost-efficacy Ratio
SECONDARY
Incremental Cost-utility Ratio

Summary

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.

Eligibility Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00733343). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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