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| [ Print-friendly version ] |
| Treatment of sleep-disordered breathing with predominant central sleep apnoea by adaptive Servo-ventilation in patients with Heart Failure |
| ISRCTN | ISRCTN19572887 |
| ClinicalTrials.gov identifier | NCT00733343 |
| Public title | Treatment of sleep-disordered breathing with predominant central sleep apnoea by adaptive Servo-ventilation in patients with Heart Failure |
| Scientific title | |
| Acronym | Serve-HF |
| Serial number at source | 001 |
| Study hypothesis | 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 apnoea. |
| Lay summary | |
| Ethics approval | Ethics approval received from the Freiburg Ethics Commission International (FEKI) (Germany) on the 5th November 2007 (ref: 07/2344). |
| Study design | Randomised, multicentre, international, parallel group trial, with patients randomised to either control or active treatment in 1:1 ratio |
| Countries of recruitment | France, Germany, Norway, Sweden, United Kingdom, United States of America |
| Disease/condition/study domain | Heart failure with sleep disordered breathing |
| Participants - inclusion criteria |
1. At least 18 years old
2. Chronic heart failure (at least 12 weeks since diagnosis) according to the current applicable guidelines (European Society of Cardiology [ESC], American College of Cardiology [ACC]/American Heart Association [AHA]) 3. Left ventricular systolic dysfunction (left ventricular ejection fraction [LVEF] less than 40% by imaging method such as echocardiography, radionuclide angiography, left ventriculography, or cardiac magnetic resonance imaging) documented less than 12 weeks before randomisation 4. New York Heart Association (NYHA) class III or IV at the time of inclusion or NYHA class II with at least one hospitalisation for heart failure (HF) in the last 12 months 5. No hospitalisation for HF for at least 4 weeks prior to inclusion 6. 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 angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) antagonists the reasons must be documented 7. SDB (Apnoea-Hypopnoea Index [AHI] greater than 15/hour with greater than or equal to 50% central events and a central AHI greater than or equal to 10 hours, 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 8. Patient is able to fully understand study information and signed informed consent |
| Participants - exclusion criteria |
1. Significant chronic obstructive pulmonary disease (COPD) with forced expiratory volume within one second (FEV1) less than 50% (European Respiratory Society criteria) in the last four weeks before randomisation
2. Oxygen saturation at rest during the day less than or equal to 90% at inclusion 3. Current use of positive airway pressure (PAP) therapy 4. Life expectancy less than 1 year for diseases unrelated to chronic HF 5. Cardiac surgery, percutaneous coronary intervention (PCI), myocardial infarction (MI) or unstable angina within 6 months prior to randomisation 6. Cardiac resynchronisation therapy (CRT)-implantation or implanatable cardioverter-defibrillator (ICD)-implantation scheduled or within 6 months prior to randomisation 7. Transient ischaemic attack (TIA) or stroke within 3 months prior to randomisation 8. Primary haemodynamically significant uncorrected valvular heart disease, obstructive or regurgitant, or any valvular disease expected to lead to surgery during the trial 9. Acute myocarditis/pericarditis within 6 months prior to randomisation 10. Untreated or therapy refractory restless legs-syndrome (RLS) 11. Pregnancy |
| Anticipated start date | 15/11/2007 |
| Anticipated end date | 30/11/2011 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 1,260 |
| Interventions |
Intervention: Adaptive servo-ventilation.
The clinical study plan provides direct clinical visits of every patient at study entry, after 2 weeks, after 3 and 12 months, thereafter every 12 months until the end of the total study. Additionally to clinical follow up visits all patients will be called by the study sites 6, 18 and thereafter every 12 months after study entry and an event history is taken by phone. At 2 weeks follow-up (FU) a device download, a physical and cardiologic examination and adverse-event (AE)-monitoring will be performed. The baseline visit, the 3, 12 and 24 months FU, thereafter every twelve months follow up visit at the site will additionally include a polysomnography (PSG) and blood samples, data collection of quality of life, data collection of sleepiness, a 6MWT (six minute walking test) and an electrocardiogram (ECG). Further a data download from the investigational device is performed. In addition, a general and event history for the time period since the last visit is established and a physical examination is performed. PSG during the FU period will be performed only on patients who are randomised to treatment group. The 2 weeks FU-visit should be performed within ± 3 days, the other FU-visits should be performed within ± 2 weeks. There will be no sham-positive airway pressure treatment in the control arm. Patients will be followed up on average for a period of 33 months. Minimum follow up time will be 24 months, maximum about 45 months. Joint Principal Investigator (for all countries except Germany): Professor Martin Cowie National Heart and Lung Institute (NHLI) Brompton Campus Dovehouse Street London, SW3 6LY United Kingdom Phone: +44 (0)20 7351 8858 E-mail: m.cowie@imperial.ac.uk |
| Primary outcome measure(s) |
The primary target parameters are defined as time to first event of:
1. All cause mortality or unplanned hospitalisation for worsening heart failure 2. Cardiovascular mortality or unplanned hospitalisation for worsening heart failure 3. All cause mortality or all cause hospitalisation The three combinations are not tested in parallel but in this hierarchical order: "Cardiovascular mortality" and "unplanned hospitalisation for worsening heart failure" will be evaluated by the Endpoint Review Committee (ERC). Definition will be documented in rules of procedure of the ERC. Heart transplantation will be counted as death. It is assumed, that the intervention reduces the hazard rate by 20% and that the event rate in the control group is 35% in the first year. It is also assumed that the hazard rate is constant over time. The primary target parameters will be measured at the final assessment. |
| Secondary outcome measure(s) |
The secondary target parameters are:
1. Time until death 2. Time until non cardiovascular death 3. Time until cardiovascular death 4. Time until unplanned hospitalisation due to worsening of heart failure or cardiovascular death 5. Time until unplanned hospitalisation for other reasons or death 6. Time until unplanned hospitalisation for cardiovascular cause or cardiovascular death 7. Time to first adequate shock in patients with ICD (evaluation of appropriateness will also be made by the ERC) or cardiovascular death 8. Percent of follow up days which patient survives and is not hospitalised for cardiovascular cause 9. Percent of follow up days which patient survives and is not hospitalised for other reasons 10. Changes in NYHA classification as compared to baseline 11. Difference in health costs between the two treatment groups 12. Changes in Quality of Life (QoL) (Minnesota) as compared to baseline 13. Changes in renal function (based on serum creatinine) as compared to baseline 14. Changes in Six Minute Walking Distance (6MWD) as compared to baseline 15. Number and cost of hospitalisations (with tariff/Diagnosis-Related Groups [DRG], diagnoses and procedures for calculating DRG or length of stay and level of care provided) 16. Cost of care (technology and service, nursing, physicians visit) related to ventilation 17. Difference in utilities/QoL (Minnesota and EQ5D) compared to control arm 18. Difference in cost of resources consumed 19. Cost-efficacy 20. Cost-utility Secondary target parameters will be measured at the last follow up or at the last available observation within FU. |
| Sources of funding | ResMed GmbH & Co. KG (Germany) |
| Trial website | http://serve-hf.ikkf.de |
| Publications | |
| Contact name | Prof Helmut Teschler |
| Address |
Ruhrlandklinik
Abt. Pneumologie Universitätsklinik Essen |
| City/town | Essen |
| Zip/Postcode | D-45239 |
| Country | Germany |
| Sponsor | ResMed GmbH & Co. KG (Germany) |
| Address | Fraunhoferstr. 16 |
| City/town | Martinsried |
| Zip/Postcode | 82152 |
| Country | Germany |
| Sponsor website: | http://www.resmed.com/de-de/ |
| Date applied | 31/10/2007 |
| Last edited | 01/12/2008 |
| Date ISRCTN assigned | 15/11/2007 |
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| © 2012 ISRCTN unless otherwise stated. | |
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