Treatment of Predominant Central Sleep Apnoea by Adaptive... | NCT00733343

ID	Type	Description	Link
ISRCTN19572887	Other Identifier	International Standard Randomised Controlled Trials

Status Module

Name	Class
CRI-The Clinical Research Institute GmbH	INDUSTRY

Description Module

Detailed Description

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:

all cause mortality or unplanned hospitalisation/prolongation of hospitalisation for worsening heart failure
cardiovascular mortality or unplanned hospitalisation/prolongation of hospitalisation for worsening heart failure.
all cause mortality or all cause unplanned hospitalisation/prolongation of hospitalisation Heart transplantation, appropriate shock from implantable cardioverter-defibrillator (ICD), long term assist device (LTAD) insertion and survived resuscitation of sudden cardiac arrest are counted as cardiovascular death, survived resuscitation for other reasons is counted as all cause death.

The three combinations are not tested in parallel but in this hierarchical order.

Secondary Endpoints : Time until death, non cardiovascular death, cardiovascular death, hospitalization due to deterioration of heart failure or cardiovascular death, hospitalization for other reasons or death, hospitalization for cardiovascular cause or cardiovascular death, percent of follow-up (FU) days which patient survives and is not hospitalized for cardiovascular cause, percent of follow up days which patient survives and is not hospitalized for other reason, time to first adequate shock (in patients with ICD, evaluation of appropriateness will also be made by the ERC) or cardiovascular death, changes in NYHA class as compared to baseline, changes in difference in health costs between the two treatment groups, changes in QoL (Minnesota, Euroqol 5D (EQ5D)) as compared to baseline, changes in renal function (based on serum creatinine) as compared to baseline, changes in result of Six Minute Walking Test (6MWT) (50) as compared to baseline,changes of AHI and oxygen desaturation index compared to baseline, AHI below 10 per hour at twelve months and Oxygen desaturation index (ODI) below 5 per hour at twelve months, atrial fibrillation at follow-up visits.

Number and cost of hospitalizations (with tariff/diagnostic-related Group (DRG), diagnoses and procedures for calculating DRG or length of stay and level of care provided), cost of care (technology and service, nursing, physicians visit) related to ventilation, difference in utilities / QoL (Minnesota and EQ5D) compared to control arm, difference in cost of resources consumed, cost-efficacy, cost-utility. Secondary target parameters will be measured at the last follow up or at the last available observation within FU.

Scheduled follow up : Minimum follow up time will be 24 months, maximum about 70 months. There will be a final assessment for each patient at the end of the study.

Label	Type	Description	Intervention Names
Treatment Group	Active Comparator	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP (Variable Positive Airway Pressure) Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA)	Device: Europe: AutoSet CS (USA: VPAP Adapt SV)
Control Group	No Intervention	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Name	Type	Description	Arm Group Labels	Other Names
Europe: AutoSet CS (USA: VPAP Adapt SV)	Device	At least 3 hours average daily usage time	Treatment Group

Measure	Description	Time Frame
All Cause Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure		time to first event, assessed for up to 70 weeks
Cardiovascular Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure		time to first event, assessed for up to 70 weeks
All Cause Mortality or All Cause Unplanned Hospitalisation/Prolongation of Hospitalisation		time to first event, assessed for up to 70 weeks

Measure	Description	Time Frame
Death From Any Cause		the last follow up or at the last available observation within Follow Up (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

Eligibility Module

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

Name	Affiliation	Role
Helmut Teschler, Prof.	Universitätsklinikum Essen	Principal Investigator
Martin Cowie, Prof.	National Heart and Lung Institute (NHLI) Brompton Hospital, London	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Westmead Hospital		Westmead	New South Wales	2145	Australia
Rivercity Private Hospital

PubMed Identifier	Type	Citation	Retractions
26886528	Result	Cowie MR, Wegscheider K, Teschler H. Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. N Engl J Med. 2016 Feb 18;374(7):690-1. doi: 10.1056/NEJMc1515007. No abstract available.
27592224	Result	Eulenburg C, Wegscheider K, Woehrle H, Angermann C, d'Ortho MP, Erdmann E, Levy P, Simonds AK, Somers VK, Zannad F, Teschler H, Cowie MR. Mechanisms underlying increased mortality risk in patients with heart failure and reduced ejection fraction randomly assigned to adaptive servoventilation in the SERVE-HF study: results of a secondary multistate modelling analysis. Lancet Respir Med. 2016 Nov;4(11):873-881. doi: 10.1016/S2213-2600(16)30244-2. Epub 2016 Aug 31.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG000360 OG001335

Primary

Cardiovascular Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure

Posted

Count of Participants

Participants

time to first event, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Primary

All Cause Mortality or All Cause Unplanned Hospitalisation/Prolongation of Hospitalisation

Posted

Count of Participants

Participants

time to first event, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Death From Any Cause

Posted

Count of Participants

Participants

the last follow up or at the last available observation within Follow Up (FU), assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Non-cardiovascular Death

Posted

Count of Participants

Participants

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Cardiovascular Death

Posted

Count of Participants

Participants

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Unplanned Hospitalisation/Prolongation of Hospitalisation Due to Worsening of Heart Failure

Posted

Count of Participants

Participants

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Unplanned Hospitalisation/Prolongation of Hospitalisation for Other Reasons or Death

Posted

Count of Participants

Participants

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

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

Posted

Count of Participants

Participants

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

First Survived Resuscitation for Any Reason (Evaluation Will Also be Made by the ERC)

Posted

Count of Participants

Participants

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

First Survived Resuscitation of Sudden Cardiac Arrest (Evaluation Will Also be Made by the ERC)

Posted

Count of Participants

Participants

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Age Baseline

Posted

Mean

Standard Deviation

years

1 x at Baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Body Weight Baseline

Posted

Mean

Standard Deviation

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Body Mass Index (BMI) Baseline

Posted

Mean

Standard Deviation

kg/cm2

1 x baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Left Ventricular Ejection Fraction at Baseline

Posted

Mean

Standard Deviation

%total vol ventricle

1x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Blood Pressure Systolic Baseline

Posted

Mean

Standard Deviation

mm Hg

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Blood Pressure Diastolic Baseline

Posted

Mean

Standard Deviation

mm Hg

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Hemoglobine Baseline

Posted

Mean

Standard Deviation

g/dl

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Creatinine Baseline

Posted

Mean

Standard Deviation

mg/dl

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Glomerular Filtration Rate Baseline

Posted

Mean

Standard Deviation

ml/min/1.73m2

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

6-Min Walk Distance

Posted

Mean

Standard Deviation

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Epworth Sleepiness Scale (ESS)

Measure Description: ESS is a self-administered questionnaire. It contains 8 questions. Questions are rated on a 4-point Likert scale (0-3); 0= would never doze, 3=high Chance of dozing. Range of scores 0-24. Global score= sum of all item scores. Copyright (c)MW Johns

Posted

Mean

Standard Deviation

total score ESS

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Apnoea-Hypopnea-Index (AHI) at Baseline

Measure Description: The AHI is an index to describe the severity of Sleep Apnea. Apnea is cessation of breathing during sleep. Hypopnea is diminished breathing during sleep. The number of Apneas and Hypopneas are added up and divided by hours of sleep (Apneas + Hypopneas per hour). An AHI ranging from 5-15 describes mild Sleep Apnea. AHI 15-30 describes moderate Sleep Apnea. AHI >30 describes severe Sleep Apnea.

Posted

Mean

Standard Deviation

events/hour

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Central Apnoea Index/Total AHI

Measure Description: Central apneas are partial or complete cessations of airflow caused by reduced or stopped neural Stimulation of the breathing muscles. For comparison: In obstructive apneas are caused by blocked airways that shut off the air although the breathing Stimulus is working.

Posted

Mean

Standard Deviation

%central/totalapnea

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Central AHI/Total AHI at Baseline

Posted

Mean

Standard Deviation

Central/totalAHI%

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Oxygen Desaturation Index (ODI) at Baseline

Number of oxygen desaturations per hour at baseline

Posted

Mean

Standard Deviation

events/hour

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Oxygen Saturation Baseline

Posted

Mean

Standard Deviation

%total hemoglobine

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Time With Oxygen Saturation Below 90%

Posted

Mean

Standard Deviation

min

1 x at baseline

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Time Until Unplanned Hospitalisation/Prolongation of Hospitalisation for Cardiovascular Cause or Cardiovascular Death/ Time Frame

Data have not been collected.

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Percent of Follow up Days Which Patient Survives and is Not Hospitalized/Hospital Stay is Not Prolonged for Cardiovascular Cause

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Changes in NYHA Classification as Compared to Baseline

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Changes in QoL (Minnesota) as Compared to Baseline

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Changes in Renal Function (Based on Serum Creatinine) as Compared to Baseline

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Changes in Six Minute Walking Distance (6MWD) as Compared to Baseline

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Changes of AHI and Oxygen Desaturation Index Compared to Baseline

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

AHI Below 10 Per Hour at Twelve Months and ODI Below 5 Per Hour at Twelve Months

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Atrial Fibrillation at Follow-up Visits

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Number and Cost of Hospitalisations (With Tariff/DRG, Diagnoses and Procedures for Calculating DRG or Length of Stay and Level of Care Provided)

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Difference in Utilities / QoL (Minnesota and EQ5D) Compared to Control Arm

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Difference in Cost of Resources Consumed

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Incremental Cost-efficacy Ratio

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Secondary

Incremental Cost-utility Ratio

Data have not been collected

Posted

the last follow up or at the last available observation within FU, assessed for up to 70 weeks

ID	Title	Description
OG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC-american college of cardiology/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
OG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Assessment Type	Notes	Statistical Information
Cardiovascular death	Cardiac disorders	Systematic Assessment		EG000199 events199 affected666 at risk EG001158 events158 affected659 at risk
Primary end point	General disorders		First event of death from any cause, lifesaving cardiovascular intervention, unplanned hospitalization for worsening chronic heart failure	EG000360 events360 affected666 at risk EG001335 events335 affected659 at risk
Firt secondary endpoint	Cardiac disorders		First Event of cardiovascular death, lifesaving cardiovascular Intervention, unplanned hospitalization for worsening chronic heart failure	EG000345 events345 affected666 at risk EG001317 events317 affected659 at risk
Second secondary endpoint	General disorders		First event of death from any cause, lifesaving cardiovascular intervention, unplanned hospitalization for any cause	EG000482 events482 affected666 at risk EG001465 events465 affected659 at risk
Hospitalization for any cause	General disorders			EG000452 events452 affected666 at risk EG001448 events448 affected659 at risk
Unplanned hospitalization for worsening heart failure	Cardiac disorders			EG000287 events287 affected666 at risk EG001272 events272 affected659 at risk
Heart transplantation	Cardiac disorders			EG0008 events8 affected666 at risk EG00112 events12 affected659 at risk
Implantation of long-term VentricularAssistDev	Cardiac disorders			EG00016 events16 affected666 at risk EG00110 events10 affected659 at risk
Resuscitation	General disorders			EG00025 events25 affected666 at risk EG00119 events19 affected659 at risk
Resuscitation for cardiac arrest	Cardiac disorders			EG00018 events18 affected666 at risk EG00116 events16 affected659 at risk
Appropriate Shock for ventricular arrhythmia	Cardiac disorders			EG00045 events45 affected666 at risk EG00165 events65 affected659 at risk
Noncardiovascular death	General disorders			EG00033 events33 affected666 at risk EG00135 events35 affected659 at risk

ID	Term
D006333	Heart Failure
D012891	Sleep Apnea Syndromes
D018487	Ventricular Dysfunction, Left

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D001049	Apnea
D012120	Respiration Disorders
D012140	Respiratory Tract Diseases
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders
D009422	Nervous System Diseases
D018754	Ventricular Dysfunction

ID	Title	Description
BG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time
BG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Treatment Group	treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA) Europe: AutoSet CS (USA: VPAP Adapt SV): At least 3 hours average daily usage time	232	666	482	666	0	666
EG001	Control Group	standard medical therapy according to applicable guidelines (ESC, ACC/AHA)	193	659	465	659	0	659