Treatment of Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure (Serve-HF)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
The Clinical Research Institute GmbH
Information provided by (Responsible Party):
ResMed
ClinicalTrials.gov Identifier:
NCT00733343
First received: February 14, 2008
Last updated: September 18, 2014
Last verified: May 2013

February 14, 2008
September 18, 2014
February 2008
May 2015   (final data collection date for primary outcome measure)
  • 1) all cause mortality or unplanned hospitalization for worsening heart failure [ Time Frame: time to first event ] [ Designated as safety issue: No ]
  • 2) cardiovascular mortality or unplanned hospitalization for worsening heart failure [ Time Frame: time to first event ] [ Designated as safety issue: No ]
  • 3) all cause mortality or all cause hospitalization [ Time Frame: time to first event ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00733343 on ClinicalTrials.gov Archive Site
  • Time until death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until non-cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until unplanned hospitalization due to worsening of heart failure or cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until unplanned hospitalization for other reasons or death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until unplanned hospitalization for cardiovascular cause or cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time to first adequate shock in patients with ICD (evaluation of appropriateness will also be made by the ERC) or cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Percent of follow up days which patient survives and is not hospitalized for cardiovascular cause [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Percent of follow up days which patient survives and is not hospitalized for other reasons [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Changes in NYHA classification as compared to baseline [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Difference in health costs between the two treatment groups [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Changes in QoL (Minnesota) as compared to baseline [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Changes in renal function (based on serum creatinine) as compared to baseline [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Changes in Six Minute Walking Distance (6MWD) (50) as compared to baseline [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Number and cost of hospitalisations (with tariff/DRG, diagnoses and procedures for calculating DRG or length of stay and level of care provided) [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Cost of care (technology and service, nursing, physicians visit) related to ventilation [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Difference in utilities / QoL (Minnesota and EQ5D) compared to control arm [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Difference in cost of resources consumed [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Cost-efficacy [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Cost-utility [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • AHI and oxygen desaturation index [ Time Frame: Compared to baseline ] [ Designated as safety issue: No ]
    Changes of AHI and oxygen desaturation index compared to baseline
  • Changes in AHI and ODI [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    AHI below 10 per hour at twelve months and ODI below 5 per hour at twelve months
  • Atrial Fibrillation [ Time Frame: n.a. ] [ Designated as safety issue: No ]
    Atrial fibrillation at follow-up visits
  • Time until death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until non-cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until unplanned hospitalization due to worsening of heart failure or cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until unplanned hospitalization for other reasons or death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time until unplanned hospitalization for cardiovascular cause or cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Time to first adequate shock in patients with ICD (evaluation of appropriateness will also be made by the ERC) or cardiovascular death [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Percent of follow up days which patient survives and is not hospitalized for cardiovascular cause [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Percent of follow up days which patient survives and is not hospitalized for other reasons [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Changes in NYHA classification as compared to baseline [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Difference in health costs between the two treatment groups [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Changes in QoL (Minnesota) as compared to baseline [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Changes in renal function (based on serum creatinine) as compared to baseline [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Changes in Six Minute Walking Distance (6MWD) (50) as compared to baseline [ Time Frame: the last follow up or at the last available observation within FU ] [ Designated as safety issue: No ]
  • Number and cost of hospitalisations (with tariff/DRG, diagnoses and procedures for calculating DRG or length of stay and level of care provided) [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Cost of care (technology and service, nursing, physicians visit) related to ventilation [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Difference in utilities / QoL (Minnesota and EQ5D) compared to control arm [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Difference in cost of resources consumed [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Cost-efficacy [ Time Frame: End of the study ] [ Designated as safety issue: No ]
  • Cost-utility [ Time Frame: End of the study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Treatment of Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure
Treatment of Sleep-Disordered Breathing With Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure

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.

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), 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, radionuclidventriculography 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:

  1. all cause mortality or unplanned hospitalization for worsening heart failure
  2. cardiovascular mortality or unplanned hospitalization for worsening heart failure.
  3. all cause mortality or all cause hospitalization Heart transplantation, appropriate shock from ICD 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 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 ODI below 5 per hour at twelve months, atrial fibrillation at follow-up visits.

Number and cost of hospitalizations (with tariff/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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Heart Failure
  • Sleep Disordered Breathing
Device: Europe: AutoSet CS 2 (USA: VPAP Adapt SV)
At least 3 hours average daily usage time
  • Active Comparator: Treatment Group
    treatment with Adaptive Servoventilation + standard medical therapy according to applicable guidelines (ESC, ACC/AHA)
    Intervention: Device: Europe: AutoSet CS 2 (USA: VPAP Adapt SV)
  • No Intervention: Control Group
    standard medical therapy according to applicable guidelines (ESC, ACC/AHA)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1313
May 2015
May 2015   (final data collection date for primary outcome measure)

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 inhibitors/ ARB 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/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 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-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
Both
22 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Czech Republic,   Denmark,   Finland,   France,   Germany,   Netherlands,   Norway,   Sweden,   Switzerland,   United Kingdom
 
NCT00733343
01, ISRCTN19572887
Yes
ResMed
ResMed
The Clinical Research Institute GmbH
Principal Investigator: Helmut Teschler, Prof. Universitätsklinikum Essen
Principal Investigator: Martin Cowie, Prof. National Heart and Lung Institute (NHLI) Brompton Hospital, London
ResMed
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP