Clinical trial NCT01164592: Substudy on the Mechanistic Plausibility of the Clinical Benefits of Adaptive Servo-ventilation
Official title: SERVE-HF: Substudy on the Mechanistic Plausibility of the Clinical Benefits of Adaptive Servo-ventilation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Failure
Sleep Disorder
Cheyne Stokes Respiration
Keywords: Heart failure (HF)
Sleep disordered breathing (SDB)
Cheyne Stokes Respiration (CSR)
Adaptive Servoventilation (ASV)
Lead sponsor: ResMed
Sponsor class: INDUSTRY
First posted: 2010-07-16
Enrollment: 312
Sex: ALL
Minimum age (years): 22
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess changes in left ventricular performance using echocardiography as well as ventricular remodelling, changes in sleep and changes in mood, anxiety and cognitive functions occurring as a result of treatment of predominant central sleep apnoea by adaptive servoventilation (ASV) in chronic heart failure in addition to optimal medical therapy in chronic heart failure. This will be a substudy of the SERVE-HF study.

Detailed description: This substudy is performed within the SERVE-HF Study, a randomised, multi-centre,international trial with parallel group design, with patients randomised to either control (optimal medical management) or active treatment (optimal medical treatment plus use of adaptive servoventilation) in a 1:1 ratio. The randomization will be the same as in the parent study. For this purpose, the randomization of the parent study will be stratified as to whether a patient is included in the substudy or not. 300 patients will be recruited for the substudy overall.

For the purpose of this substudy, patients will be followed up for a period of 12 months.

The following extra tests will be performed at the baseline visit, the 3 months follow up and the 12 months follow up:

* Echocardiogram (for both groups)
* cMRI (for both groups)
* PSG (at the baseline visit only for patients in the treatment group and at 3 months follow up and the 12 months follow up for all patients)
* 4 questionnaires (for both groups)
* Additional blood testing (for both groups)

Eligibility criteria: The inclusion and exclusion criteria are mainly those applicable for the parent study; SERVE-HF. The inclusion and exclusion criteria are listed here.

INCLUSION CRITERIA FOR SERVE-HF STUDY:

* Over 22 years of age
* Severe Chronic Heart Failure (CHF) with NYHA class III-IV or NYHA class II with at least one hospitalisation for HF within the last 24 months
* Left ventricular ejection fraction (LVEF) less than or equal to 45% by means of echocardiography, radionucleotide angiography, left ventriculography or cardiac MRI documented less than 12 weeks before randomisation
* Diagnosis of sleep disordered breathing (SDB) with an apnoea-hypopnoea-index (AHI) of \>15/hr with at least 50% central events and a central AHI of at least 10/hr
* Clinically stable with no change in medication and no unplanned hospitalisation for heart failure in preceding month
* Optimised medical treatment according to the applicable guidelines
* Able to provide informed consent

ADDITIONAL INCLUSION CRITERIA FOR THE SUBSTUDY

• Predominant central sleep apnoea (apnoea hypopnoea index \> 15/hour with ≥ 50% central events and a central AHI ≥10/hour, derived from full polysomnography (based on total sleep time), documented less than 4 weeks before randomization. Flow measurements have to be performed with nasal cannula

EXCLUSION CRITERIA FOR THE SERVE-HF STUDY:

* Significant chronic obstructive pulmonary disease (COPD) with Forced Expiratory Volume within one second (FEV1)\<50% predicted
* Oxygen saturation at rest during the day 90% at the time of inclusion
* Current use of Positive Airway Pressure (PAP) therapy
* Life expectancy \< 1 year for diseases unrelated to chronic heart failure
* Cardiac surgery, Percutaneous coronary intervention (PCI), Myocardial Infarction (MI) or unstable angina within 6 months prior to randomisation
* Implantation of ICD (implanted cardiodefibrillator) or CRT (cardiac resynchronisation therapy) 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)
* Pregnancy

ADDITIONAL EXCLUSION CRITERIA FOR THE SUBSTUDY

* Amyloidosis, hypertrophic obstructive cardiomyopathy or arteriovenous fistulas
* Dosage changes of diuretics more than doubled within the last 4 weeks prior to randomisation

Primary outcomes:
measure: Change in Left Ventricular Ejection Fraction (LVEF) from baseline to 12 months of therapy as measured by echocardiography (Echo).
timeFrame: Baseline (Randomization), 6- and 12 month-Follow-up-visit
Secondary outcomes:
measure: Changes in left and right ventricular function
timeFrame: Baseline (Randomization), 6-and 12-month-Follow-up visit
measure: Changes in LV systolic and diastolic indexed volumes
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
measure: Changes in right ventricular (RV) systolic and diastolic indexed volumes
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
measure: Changes in LV and RV mass
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
measure: Changes in LV sphericity index and LV end-systolic global wall stress
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
measure: Changes in sleep duration and sleep stages as well as arousals
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
measure: Changes in sleep-disordered breathing
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
measure: Changes in quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
measure: Changes in mental status assessed by Mini-Mental State Examination (MMSE)
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
measure: Changes in Patient Health Questionnaire-9 (PHQ-9) score and Patient Anxiety Questionnaire GAD-7
timeFrame: Baseline (Randomization), 6- and 12-month-Follow-up-visit
Other outcomes:
Locations:
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Rivercity Private Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: East Melbourne
country: Australia
facility: Melbourne Sleep Disorders Centre
state: Victoria
city: Melbourne
country: Australia
facility: St. Vincents and Mercy Private Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Hollywood Private Hospital (CVS)
state: Western Australia
city: Brno
country: Czech Republic
facility: St. Anne's University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Tampere
country: Finland
facility: Unesta Research Centre
city: Tampere
country: Finland
facility: Tampere University Hospital, Pirkanmaa sairaanhoitopiiri
city: Grenoble
country: France
facility: Clinique Mutualiste des Eaux Claires
city: Grenoble
country: France
facility: CHU Grenoble, Hopital Michallon
city: Poitiers
country: France
facility: CHU de Poitiers
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Alzey
country: Germany
facility: DRK Krankenhaus
city: Bad Krozingen
country: Germany
facility: Herzzentrum Bad Krozingen
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW
city: Berlin
country: Germany
facility: Charité Campus Mitte CCM
city: Berlin
country: Germany
facility: Charité Campus Mitte
city: Berlin
country: Germany
facility: POLIKUM Friedenau
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin
city: Berlin
country: Germany
facility: Jüdisches Krankenhaus Berlin
city: Bielefeld
country: Germany
facility: Praxis für Lunge Herz und Schlaf
city: Bonn
country: Germany
facility: Kardiologische Praxis Marschner
city: Borna
country: Germany
facility: Helios Klinikum Borna
city: Brühl
country: Germany
facility: Kardiologie Brühl
city: Castrop-Rauxel
country: Germany
facility: Gemeinschaftspraxis Kardiologie Dr. Becker
city: Castrop-Rauxel
country: Germany
facility: Kardiologische Praxis Dr. Isbruch
city: Dortmund
country: Germany
facility: Praxis Dr. Hecker
city: Dortmund
country: Germany
facility: Kardiologische Praxis Dr. Wetzel
city: Dortmund
country: Germany
facility: Praxis Dr. Lodde
city: Dresden
country: Germany
facility: Facharztzentrum Dresden-Neustadt GbR
city: Dresden
country: Germany
facility: Gemeinschaftpraxis Dres. Schmidt/Gronke
city: Dresden
country: Germany
facility: Praxis Dr. Hohensee
city: Dresden
country: Germany
facility: Herzzentrum Universität Dresden
city: Duesseldorf
country: Germany
facility: Khs Florence-Nightingale
city: Düsseldorf
country: Germany
facility: Kardiologie Oberkassel
city: Düsseldorf
country: Germany
facility: Gemeinschaftspraxis PD Dr. Lankisch
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Essen
country: Germany
facility: Kardiologie Praxis Dr. Bonnekamp
city: Essen
country: Germany
facility: Praxis Dr. Tekiyeh
city: Essen
country: Germany
facility: Ruhrlandklinik Essen
city: Essen
country: Germany
facility: Kath. Kliniken Essen/ Philippusstift
city: Flonheim
country: Germany
facility: Gemeinschaftspraxis Dres. Guckenbiehl
city: Frankfurt
country: Germany
facility: CardioVaskuläres Centrum Frankfurt
city: Frechen
country: Germany
facility: Praxis Dr. Diedrichs
city: Freiburg im Breisgau
country: Germany
facility: Universitätsklinikum Freiburg
city: Gütersloh
country: Germany
facility: Kardiologische Praxis Gütersloh
city: Hagen
country: Germany
facility: Gemeinschaftspraxis Dres Leischik/Littwitz
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Barmbek
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Hemer
country: Germany
facility: Lungenklinik Hemer
city: Herne
country: Germany
facility: B&B GmbH
city: Herne
country: Germany
facility: Cardio-Praxis Herne Dr. Furche
city: Herne
country: Germany
facility: Gemeinschaftspraxis Dr. Bruch
city: Herne
country: Germany
facility: Kardiologische Praxis Dr. Schlichting
city: Herne
country: Germany
facility: Augusta-Kranken-Anstalt gGmbH Thoraxzentrum Ruhrgebiet
city: Herten
country: Germany
facility: St. Elisabeth-Hospital Herten gGmbH
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Ingelheim
country: Germany
facility: Cardiopraxis Ingelheim
city: Karlstadt
country: Germany
facility: Gemeinschaftspraxis Dres. Dobler/Turin
city: Köln
country: Germany
facility: Malteser Krankenhaus St. Hildegardis
city: Köln
country: Germany
facility: Klinikum der Universität zu Köln- Herzzentrum
city: Köln
country: Germany
facility: Klinikum der Universität zu Köln-Schlaflabor
city: Köln
country: Germany
facility: Praxis Dr. Anselm Bäumer
city: Köln
country: Germany
facility: Gemeinschaftspraxis Dres. Gysan/Heinzler/May
city: Leipzig
country: Germany
facility: Universität Leipzig -Herzzentrum
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Lübeck-Kardiologie
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Lübeck-Schlaflabor
city: Menden
country: Germany
facility: Praxis für Kardiologie Dr. med. Menz
city: Moers
country: Germany
facility: Krankenhaus Bethanien
city: Mühldorf
country: Germany
facility: Kardiologische Praxis Dr. Schön
city: Mülheim an der Ruhr
country: Germany
facility: Evangelisches Krankenhaus Mülheim
city: München
country: Germany
facility: Lungenärzte am Rotkreuzplatz
city: München
country: Germany
facility: Klinikum Augustinum München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Neuss
country: Germany
facility: Städtisches Khs Lukas
city: Nienburg
country: Germany
facility: Kardiologische Praxis Nienburg
city: Ratingen
country: Germany
facility: Praxis Dr. Fröhlich
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
city: Reinbek
country: Germany
facility: Khs St. Adolf Stift
city: Reinbek
country: Germany
facility: Praxis Dr. Hein
city: Unna
country: Germany
facility: Katharinen Hospital Unna
city: Waldkraiburg
country: Germany
facility: Praxis Dr. Gerritsen
city: Wiesbaden
country: Germany
facility: Kardiologisch angiologische Gemeinschaftspraxis
city: Wiesbaden
country: Germany
facility: Kardiologische Gemeinschaftspraxis Dr. K. Vorbeck
city: Wuerzburg
country: Germany
facility: Missionsärztliche Klinik Würzburg
city: Würzburg
country: Germany
facility: Comprehensive Heart Failure Center, Universitätsklinikum Würzburg
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Lugano
country: Switzerland
facility: Cardiocentro Ticino
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
city: London
country: United Kingdom
facility: Brompton Hospital
Study officials:
affiliation: Royal Brompton Hospital, London
name: Martin Cowie, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: ResMed
name: Holger Woehrle, MD
role: STUDY_DIRECTOR
References: