Substudy on the Mechanistic Plausibility of the Clinical Benefits of Adaptive Servo-ventilation

Heart Failure Clinical Trial

— MS  

Official title:

SERVE-HF: Substudy on the Mechanistic Plausibility of the Clinical Benefits of Adaptive Servo-ventilation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01164592
• Other study ID #: 01a
• Status: Completed
• Phase: Phase 4
• First received: July 15, 2010
• Last updated: August 4, 2015
• Start date: August 2012
• Est. completion date: June 2015

Study information

• Verified date: August 2015
• Source: ResMed
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: National Health ServiceAustralia: Human Research Ethics CommitteeNetherlands: Independent Ethics CommitteeCzech Republic: Ethics CommitteeFinland: Ethics CommitteeSwitzerland: Comitato Etico Cantone Ticino
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 312
• Est. completion date: June 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 22 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cheyne Stokes Respiration
• Cheyne-Stokes Respiration
• Heart Failure
• Parasomnias
• Sleep Disorder
• Sleep Disorders

Intervention

Device:
• adaptive servoventilation (ASV)
Patients randomised to therapygroup should use the adaptive servoventilation (ASV) device each night at least 3 hours

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Rivercity Private Hospital	Auchenflower	Queensland
Australia	Melbourne Sleep Disorders Centre	East Melbourne	Victoria
Australia	St. Vincents and Mercy Private Hospital	Melbourne	Victoria
Australia	Hollywood Private Hospital (CVS)	Nedlands	Western Australia
Australia	Westmead Hospital	Westmead	New South Wales
Czech Republic	St. Anne's University Hospital	Brno
Finland	Helsinki University Hospital	Helsinki
Finland	Tampere University Hospital, Pirkanmaa sairaanhoitopiiri	Tampere
Finland	Unesta Research Centre	Tampere
France	CHU Grenoble, Hopital Michallon	Grenoble
France	Clinique Mutualiste des Eaux Claires	Grenoble
France	CHU de Poitiers	Poitiers
Germany	Universitätsklinikum Aachen	Aachen
Germany	DRK Krankenhaus	Alzey
Germany	Herzzentrum Bad Krozingen	Bad Krozingen
Germany	Herz- und Diabeteszentrum NRW	Bad Oeynhausen
Germany	Charité Campus Mitte	Berlin
Germany	Charité Campus Mitte CCM	Berlin
Germany	Jüdisches Krankenhaus Berlin	Berlin
Germany	POLIKUM Friedenau	Berlin
Germany	Unfallkrankenhaus Berlin	Berlin
Germany	Praxis für Lunge Herz und Schlaf	Bielefeld
Germany	Kardiologische Praxis Marschner	Bonn
Germany	Helios Klinikum Borna	Borna
Germany	Kardiologie Brühl	Brühl
Germany	Gemeinschaftspraxis Kardiologie Dr. Becker	Castrop-Rauxel
Germany	Kardiologische Praxis Dr. Isbruch	Castrop-Rauxel
Germany	Kardiologische Praxis Dr. Wetzel	Dortmund
Germany	Praxis Dr. Hecker	Dortmund
Germany	Praxis Dr. Lodde	Dortmund
Germany	Facharztzentrum Dresden-Neustadt GbR	Dresden
Germany	Gemeinschaftpraxis Dres. Schmidt/Gronke	Dresden
Germany	Herzzentrum Universität Dresden	Dresden
Germany	Praxis Dr. Hohensee	Dresden
Germany	Khs Florence-Nightingale	Duesseldorf
Germany	Gemeinschaftspraxis PD Dr. Lankisch	Düsseldorf
Germany	Kardiologie Oberkassel	Düsseldorf
Germany	Kardiologie Praxis Dr. Bonnekamp	Essen
Germany	Kath. Kliniken Essen/ Philippusstift	Essen
Germany	Praxis Dr. Tekiyeh	Essen
Germany	Ruhrlandklinik Essen	Essen
Germany	Universitätsklinikum Essen	Essen
Germany	Gemeinschaftspraxis Dres. Guckenbiehl	Flonheim
Germany	CardioVaskuläres Centrum Frankfurt	Frankfurt
Germany	Praxis Dr. Diedrichs	Frechen
Germany	Universitätsklinikum Freiburg	Freiburg im Breisgau
Germany	Kardiologische Praxis Gütersloh	Gütersloh
Germany	Gemeinschaftspraxis Dres Leischik/Littwitz	Hagen
Germany	Asklepios Klinik Barmbek	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Lungenklinik Hemer	Hemer
Germany	Augusta-Kranken-Anstalt gGmbH Thoraxzentrum Ruhrgebiet	Herne
Germany	B&B GmbH	Herne
Germany	Cardio-Praxis Herne Dr. Furche	Herne
Germany	Gemeinschaftspraxis Dr. Bruch	Herne
Germany	Kardiologische Praxis Dr. Schlichting	Herne
Germany	St. Elisabeth-Hospital Herten gGmbH	Herten
Germany	Lungenfachklinik Immenhausen	Immenhausen
Germany	Cardiopraxis Ingelheim	Ingelheim
Germany	Gemeinschaftspraxis Dres. Dobler/Turin	Karlstadt
Germany	Gemeinschaftspraxis Dres. Gysan/Heinzler/May	Köln
Germany	Klinikum der Universität zu Köln- Herzzentrum	Köln
Germany	Klinikum der Universität zu Köln-Schlaflabor	Köln
Germany	Malteser Krankenhaus St. Hildegardis	Köln
Germany	Praxis Dr. Anselm Bäumer	Köln
Germany	Universität Leipzig -Herzzentrum	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein Campus Lübeck-Kardiologie	Lübeck
Germany	Universitätsklinikum Schleswig-Holstein Campus Lübeck-Schlaflabor	Lübeck
Germany	Praxis für Kardiologie Dr. med. Menz	Menden
Germany	Krankenhaus Bethanien	Moers
Germany	Kardiologische Praxis Dr. Schön	Mühldorf
Germany	Evangelisches Krankenhaus Mülheim	Mülheim an der Ruhr
Germany	Klinikum Augustinum München	München
Germany	Lungenärzte am Rotkreuzplatz	München
Germany	Universitätsklinikum Münster	Münster
Germany	Städtisches Khs Lukas	Neuss
Germany	Kardiologische Praxis Nienburg	Nienburg
Germany	Praxis Dr. Fröhlich	Ratingen
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Khs St. Adolf Stift	Reinbek
Germany	Praxis Dr. Hein	Reinbek
Germany	Katharinen Hospital Unna	Unna
Germany	Praxis Dr. Gerritsen	Waldkraiburg
Germany	Kardiologisch angiologische Gemeinschaftspraxis	Wiesbaden
Germany	Kardiologische Gemeinschaftspraxis Dr. K. Vorbeck	Wiesbaden
Germany	Missionsärztliche Klinik Würzburg	Wuerzburg
Germany	Comprehensive Heart Failure Center, Universitätsklinikum Würzburg	Würzburg
Netherlands	University Medical Center Groningen	Groningen
Switzerland	Cardiocentro Ticino	Lugano
Switzerland	Ospedale Regionale di Lugano	Lugano
United Kingdom	Brompton Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
ResMed

Countries where clinical trial is conducted

Australia,  Czech Republic,  Finland,  France,  Germany,  Netherlands,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Left Ventricular Ejection Fraction (LVEF) from baseline to 12 months of therapy as measured by echocardiography (Echo).		Baseline (Randomization), 6- and 12 month-Follow-up-visit	Yes
Secondary	Changes in left and right ventricular function		Baseline (Randomization), 6-and 12-month-Follow-up visit	Yes
Secondary	Changes in LV systolic and diastolic indexed volumes		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes
Secondary	Changes in right ventricular (RV) systolic and diastolic indexed volumes		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes
Secondary	Changes in LV and RV mass		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes
Secondary	Changes in LV sphericity index and LV end-systolic global wall stress		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes
Secondary	Changes in sleep duration and sleep stages as well as arousals		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes
Secondary	Changes in sleep-disordered breathing		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes
Secondary	Changes in quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes
Secondary	Changes in mental status assessed by Mini-Mental State Examination (MMSE)		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes
Secondary	Changes in Patient Health Questionnaire-9 (PHQ-9) score and Patient Anxiety Questionnaire GAD-7		Baseline (Randomization), 6- and 12-month-Follow-up-visit	Yes