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

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Sleep Disorder; Cheyne Stokes Respiration
• Intervention / Treatment: Device: adaptive servoventilation (ASV)

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)

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Rivercity Private Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Melbourne Sleep Disorders Centre
    • Melbourne, Victoria, Australia, 3065
      • St. Vincents and Mercy Private Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Hollywood Private Hospital (CVS)
• Czech Republic
  • Brno, Czech Republic, 65691
    • St. Anne's University Hospital
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Hospital
  • Tampere, Finland, 33520
    • Unesta Research Centre
  • Tampere, Finland, 33521
    • Tampere University Hospital, Pirkanmaa sairaanhoitopiiri
• France
  • Grenoble, France, 38000
    • Clinique Mutualiste des Eaux Claires
  • Grenoble, France, 38043
    • CHU Grenoble, Hopital Michallon
  • Poitiers, France, 86000
    • CHU de Poitiers
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen
  • Alzey, Germany, 55232
    • DRK Krankenhaus
  • Bad Krozingen, Germany, 79189
    • Herzzentrum Bad Krozingen
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW
  • Berlin, Germany, 12683
    • Unfallkrankenhaus Berlin
  • Berlin, Germany, 10117
    • Charité Campus Mitte
  • Berlin, Germany, 10117
    • Charité Campus Mitte CCM
  • Berlin, Germany, 12157
    • POLIKUM Friedenau
  • Berlin, Germany, 13347
    • Jüdisches Krankenhaus Berlin
  • Bielefeld, Germany, 33617
    • Praxis für Lunge Herz und Schlaf
  • Bonn, Germany, 53225
    • Kardiologische Praxis Marschner
  • Borna, Germany, 04552
    • Helios Klinikum Borna
  • Brühl, Germany, 50321
    • Kardiologie Brühl
  • Castrop-Rauxel, Germany, 44575
    • Gemeinschaftspraxis Kardiologie Dr. Becker
  • Castrop-Rauxel, Germany, 44577
    • Kardiologische Praxis Dr. Isbruch
  • Dortmund, Germany, 44135
    • Praxis Dr. Hecker
  • Dortmund, Germany, 44141
    • Kardiologische Praxis Dr. Wetzel
  • Dortmund, Germany, 44147
    • Praxis Dr. Lodde
  • Dresden, Germany, 01099
    • Facharztzentrum Dresden-Neustadt GbR
  • Dresden, Germany, 01219
    • Gemeinschaftpraxis Dres. Schmidt/Gronke
  • Dresden, Germany, 01277
    • Praxis Dr. Hohensee
  • Dresden, Germany, 01307
    • Herzzentrum Universität Dresden
  • Duesseldorf, Germany, 40489
    • Khs Florence-Nightingale
  • Düsseldorf, Germany, 40545
    • Kardiologie Oberkassel
  • Düsseldorf, Germany, 40597
    • Gemeinschaftspraxis PD Dr. Lankisch
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
  • Essen, Germany, 45239
    • Ruhrlandklinik Essen
  • Essen, Germany, 45136
    • Kardiologie Praxis Dr. Bonnekamp
  • Essen, Germany, 45136
    • Praxis Dr. Tekiyeh
  • Essen, Germany, 45359
    • Kath. Kliniken Essen/ Philippusstift
  • Flonheim, Germany, 55237
    • Gemeinschaftspraxis Dres. Guckenbiehl
  • Frankfurt, Germany, 60389
    • CardioVaskuläres Centrum Frankfurt
  • Frechen, Germany, 50226
    • Praxis Dr. Diedrichs
  • Freiburg im Breisgau, Germany, 79106
    • Universitätsklinikum Freiburg
  • Gütersloh, Germany, 33330
    • Kardiologische Praxis Gütersloh
  • Hagen, Germany, 58095
    • Gemeinschaftspraxis Dres Leischik/Littwitz
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Hamburg, Germany, 22291
    • Asklepios Klinik Barmbek
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • Hemer, Germany, 58675
    • Lungenklinik Hemer
  • Herne, Germany, 44629
    • Gemeinschaftspraxis Dr. Bruch
  • Herne, Germany, 44649
    • Kardiologische Praxis Dr. Schlichting
  • Herne, Germany, 44623
    • B&B GmbH
  • Herne, Germany, 44623
    • Cardio-Praxis Herne Dr. Furche
  • Herne, Germany, 44651
    • Augusta-Kranken-Anstalt gGmbH Thoraxzentrum Ruhrgebiet
  • Herten, Germany, 45699
    • St. Elisabeth-Hospital Herten gGmbH
  • Immenhausen, Germany, 34376
    • Lungenfachklinik Immenhausen
  • Ingelheim, Germany, 55218
    • Cardiopraxis Ingelheim
  • Karlstadt, Germany, 97753
    • Gemeinschaftspraxis Dres. Dobler/Turin
  • Köln, Germany, 50931
    • Malteser Krankenhaus St. Hildegardis
  • Köln, Germany, 50937
    • Klinikum der Universität zu Köln- Herzzentrum
  • Köln, Germany, 51065
    • Praxis Dr. Anselm Bäumer
  • Köln, Germany, 51105
    • Gemeinschaftspraxis Dres. Gysan/Heinzler/May
  • Köln, Germany, 50937
    • Klinikum der Universität zu Köln-Schlaflabor
  • Leipzig, Germany, 04289
    • Universität Leipzig -Herzzentrum
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein Campus Lübeck-Kardiologie
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein Campus Lübeck-Schlaflabor
  • Menden, Germany, 58706
    • Praxis Für Kardiologie Dr. med. Menz
  • Moers, Germany, 47441
    • Krankenhaus Bethanien
  • Mühldorf, Germany, 84453
    • Kardiologische Praxis Dr. Schön
  • Mülheim an der Ruhr, Germany, 45468
    • Evangelisches Krankenhaus Mülheim
  • München, Germany, 81375
    • Klinikum Augustinum München
  • München, Germany, 80634
    • Lungenärzte am Rotkreuzplatz
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
  • Neuss, Germany, 41472
    • Städtisches Khs Lukas
  • Nienburg, Germany, 31582
    • Kardiologische Praxis Nienburg
  • Ratingen, Germany, 40885
    • Praxis Dr. Fröhlich
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
  • Reinbek, Germany, 21465
    • Khs St. Adolf Stift
  • Reinbek, Germany, 21465
    • Praxis Dr. Hein
  • Unna, Germany, 59423
    • Katharinen Hospital Unna
  • Waldkraiburg, Germany, 84478
    • Praxis Dr. Gerritsen
  • Wiesbaden, Germany, 65183
    • Kardiologisch angiologische Gemeinschaftspraxis
  • Wiesbaden, Germany, 65183
    • Kardiologische Gemeinschaftspraxis Dr. K. Vorbeck
  • Wuerzburg, Germany, 97074
    • Missionsärztliche Klinik Würzburg
  • Würzburg, Germany, 97080
    • Comprehensive Heart Failure Center, Universitätsklinikum Würzburg
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • University Medical Center Groningen
• Switzerland
  • Lugano, Switzerland, 6900
    • Cardiocentro Ticino
  • Lugano, Switzerland, 6903
    • Ospedale Regionale di Lugano
• United Kingdom
  • London, United Kingdom, UK-SW36NP
    • Brompton Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Therapy with adaptive servo ventilation; optimal medical therapy + adaptive servoventilation	Device: adaptive servoventilation (ASV); Patients randomised to therapygroup should use the adaptive servoventilation (ASV) device each night at least 3 hours; Other Names: Adaptive Servo-Ventilation with AutoSet CS
NO_INTERVENTION: Optimal medical therapy according to guidelines; optimal medical therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in left and right ventricular function	Baseline (Randomization), 6-and 12-month-Follow-up visit
Changes in LV systolic and diastolic indexed volumes	Baseline (Randomization), 6- and 12-month-Follow-up-visit
Changes in right ventricular (RV) systolic and diastolic indexed volumes	Baseline (Randomization), 6- and 12-month-Follow-up-visit
Changes in LV and RV mass	Baseline (Randomization), 6- and 12-month-Follow-up-visit
Changes in LV sphericity index and LV end-systolic global wall stress	Baseline (Randomization), 6- and 12-month-Follow-up-visit
Changes in sleep duration and sleep stages as well as arousals	Baseline (Randomization), 6- and 12-month-Follow-up-visit
Changes in sleep-disordered breathing	Baseline (Randomization), 6- and 12-month-Follow-up-visit
Changes in quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)	Baseline (Randomization), 6- and 12-month-Follow-up-visit
Changes in mental status assessed by Mini-Mental State Examination (MMSE)	Baseline (Randomization), 6- and 12-month-Follow-up-visit
Changes in Patient Health Questionnaire-9 (PHQ-9) score and Patient Anxiety Questionnaire GAD-7	Baseline (Randomization), 6- and 12-month-Follow-up-visit

Collaborators and Investigators

• Sponsor: ResMed
• Investigators: Principal Investigator: Martin Cowie, Prof, Royal Brompton Hospital, London

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ACTUAL): April 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: July 15, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (ESTIMATE): July 16, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): August 7, 2015
• Last Update Submitted That Met QC Criteria: August 4, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Adaptive Servoventilation (ASV); Heart failure (HF); Sleep disordered breathing (SDB); Cheyne Stokes Respiration (CSR)
• Additional Relevant MeSH Terms: Mental Disorders; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Neurologic Manifestations; Signs and Symptoms, Respiratory; Heart Failure; Sleep Wake Disorders; Cheyne-Stokes Respiration
• Other Study ID Numbers: 01a