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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Sleep Disordered Breathing
• Intervention / Treatment: Device: Europe: AutoSet CS (USA: VPAP Adapt SV)

Detailed Description

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), New York Heart Association (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, radionuclide ventriculography 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 hospitalisation/prolongation of hospitalisation for worsening heart failure
2. cardiovascular mortality or unplanned hospitalisation/prolongation of hospitalisation for worsening heart failure.
3. all cause mortality or all cause unplanned hospitalisation/prolongation of hospitalisation Heart transplantation, appropriate shock from implantable cardioverter-defibrillator (ICD), long term assist device (LTAD) insertion 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 (FU) 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 Oxygen desaturation index (ODI) below 5 per hour at twelve months, atrial fibrillation at follow-up visits.

Number and cost of hospitalizations (with tariff/diagnostic-related Group (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.

• Study Type: Interventional
• Enrollment (Actual): 1325
• Phase: Not Applicable

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)
• Czechia
  • Brno, Czechia, 65691
    • St. Anne's University Hospital Brno
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Copenhagen, Denmark, 2400
    • Bispebjerg Hospital
  • Glostrup, Denmark, 2600
    • Glostrup Hospital
  • Glostrup, Denmark, 2600
    • Dansk Center For Søvnmedicin
  • Århus C, Denmark, 8000
    • Århus Universitets Hospital
  • Århus N, Denmark, 8200
    • Århus Universitets Hospital Skejby
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Hospital
  • Tampere, Finland, 33520
    • Unesta Research Centre
  • Tampere, Finland, 33521
    • Tampere University Hospital, Pirkanmaa sairaanhoitopiiri
• France
  • Amneville, France, 57360
    • Cardiologist Dr. Papola
  • Angers, France, 49933
    • CHU Angers
  • Antibes, France, 06606
    • Centre Hospitalier d'Antibes Juan-les-Pins
  • Antony, France, 92166
    • Hopital Prive d'Antony
  • Belfort, France, 90000
    • CH Belfort
  • Besancon, France, 25000
    • CH de Besançon
  • Beziers, France, 34525
    • Centre Hospitalier de Béziers
  • Bordeaux, France, 33000
    • Clinique du Tondu
  • Bordeaux, France, 33000
    • Hôpital St. André
  • Bordeaux, France, 33000
    • Praxis Cardiologique Dr. Puel
  • Bordeaux, France, 33000
    • Praxis Cardiologique Dr. Wickers
  • Bordeaux, France, 33076
    • CHU Bordeaux, Hôpital Pellegrin
  • Caen Cedex, France, 14033
    • CHU de Caen
  • Cannes, France, 06401
    • Centre Hospitalier de Cannes
  • Creteil, France, 94010
    • Hopital Henri Mondor
  • Echirolles, France, 38434
    • Hopital Sud
  • Forbach, France, 57604
    • CH de Forbach, Hospitalor, Hopital Marie Madeleine-Pneumology
  • Forbach, France, 57604
    • CH de Forbach-Cardiology
  • Grenoble, France, 38000
    • Clinique Mutualiste des Eaux Claires
  • Grenoble, France, 38043
    • CHU Grenoble, Hopital Michallon
  • Haguenau, France, 67504
    • CH Haguenau
  • L'Union, France, 31240
    • Clinique de l'Union
  • Lille, France, 59037
    • CHU Lille- Hopital Cardiologique
  • Lille, France, 59037
    • CHU Lille-Sleep medicine
  • Lille, France, 59042
    • Polyclinique La Louviere
  • Lyon, France, 69317
    • Hospices Civils de Lyon, Hopital de la Croix-Rousse
  • Metz, France, 57000
    • CHR Metz, Hôpital de Bon-Secours
  • Montbeliard, France, 25209
    • CH Montbeliard
  • Montpellier, France, 34295
    • CHU de Montpellier
  • Montreuil, France, 93105
    • CH Intercommunal André Grégoire
  • Mulhouse, France, 68070
    • CH de Mulhouse, Hopital Emile Muller
  • Ollioules, France, 83190
    • Clinique les Fleurs
  • Paris, France, 75018
    • Hopital Bichat
  • Paris, France, 75790
    • CHU Tenon
  • Pessac, France, 33600
    • CHU de Bordeaux, Hopital Haut Leveque
  • Poitiers, France, 86000
    • CHU de Poitiers
  • Pont-à-mousson, France, 54700
    • Cabinet de cardiologie
  • Pontoise, France, 95303
    • CH René Dubos
  • Rennes, France, 35706
    • Polyclinique Saint-Laurent
  • Rouen, France, 76031
    • CHU de Rouen, Hopital de Bois Guillaume
  • Saint Avold, France, BP 30011
    • CH Lemire - St Avold
  • Saint Louis, France, 68300
    • Clinique des Trois Frontières
  • Saint- Etienne, France, 42055
    • CHU de Saint-Etienne, Hopital Nord
  • St Dié des Vosges, France, 88187
    • CH de St Dié des Vosges
  • Toulouse, France, 31059
    • CHU Toulouse, Hopital de Rangueil
  • Toulouse, France, 31059
    • CHU Toulouse, Hôpital Larrey
  • Trouville, France, 14360
    • CH Trouville
  • Vandoeuvre les Nancy, France, 54511
    • CHU de Nancy, Hôpital Brabois
  • Verdun, France, 55100
    • Ch St. Nicolas
• Germany
  • Aachen, Germany, 52074
    • Universitätsklinikum Aachen
  • Aachen, Germany, 52062
    • Praxis Dr. Frieske
  • Alzey, Germany, 55232
    • DRK Krankenhaus
  • Arnsberg, Germany, 59821
    • Gemeinschaftspraxis Weiß / Dr. Heesing
  • Bad Berka, Germany, 99437
    • Zentralklinikum Bad Berka
  • Bad Krozingen, Germany, 79189
    • Herzzentrum Bad Krozingen
  • Bad Krozingen, Germany, 79189
    • Klinik Lazariterhof
  • Bad Krozingen, Germany, 79189
    • Schlaflabor Breisgau
  • Bad Mergentheim, Germany, 97980
    • Praxis Dr. Bauer
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW
  • Bautzen, Germany, 02625
    • Oberlausitz-Kliniken gGmbH
  • Bergheim, Germany, 50126
    • Kardiologie Brühl
  • Bergisch Gladbach, Germany, 51465
    • Kardiopraxis Rheinberg
  • Berlin, Germany, 12683
    • Unfallkrankenhaus Berlin
  • Berlin, Germany, 13353
    • Charite Campus Virchow Klinikum
  • Berlin, Germany, 12157
    • POLIKUM Friedenau
  • Berlin, Germany, 12355
    • Gemeinschaftspraxis Groß-Ziethener Chaussee
  • Berlin, Germany, 13347
    • Jüdisches Krankenhaus Berlin
  • Berlin, Germany, 14050
    • Praxis Westend
  • Berlin, Germany, 10117
    • Charité Campus Mitte - Kardiologie
  • Berlin, Germany, 10117
    • Charité Campus Mitte CCM- Schlafmedizinisches Zentrum
  • Berlin, Germany, 13125
    • Evangelische Lungenfachklinik Buch
  • Bernau, Germany, 16321
    • Herzzentrum Brandenburg
  • Bielefeld, Germany, 33617
    • Praxis für Lunge, Herz und Schlaf
  • Bochum, Germany, 44789
    • Universitätsklinikum Bergmannsheil
  • Bochum, Germany, 44791
    • Augusta Krankenanstalten Bochum
  • Bochum, Germany, 44791
    • St.-Josephs-Hospital
  • Bochum, Germany, 44797
    • Kardiologie Kemnade
  • Bochum, Germany, 44866
    • Kardiologische Praxis Dr. Staubach
  • Bochum, Germany, 44787
    • Kardiologie Gemeinschaftspraxis Dres Tenholt&Metzger&Dexling
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • Bonn, Germany, 53225
    • Kardiologische Praxis Marschner
  • Borna, Germany, 04552
    • Helios Klinikum Borna
  • Bottrop, Germany, 46236
    • Gemeinschaftspraxis Kardiologie
  • Bremen, Germany, 28325
    • Klinikum Bremen Ost
  • Brühl, Germany, 50321
    • Kardiologie Brühl
  • Burg, Germany, 03096
    • Mediclin Rehazentrum Spreewald
  • Castrop-Rauxel, Germany, 44575
    • Gemeinschaftspraxis Kardiologie Dr. Becker
  • Castrop-Rauxel, Germany, 44577
    • Kardiologische Praxis Dr. Isbruch
  • Chemnitz, Germany, 09113
    • MVZ am Küchwald
  • Coburg, Germany, 96450
    • Klinikum Coburg GmbH
  • Coswig, Germany, 01640
    • Fachkrankenhaus Coswig
  • Cottbus, Germany, 03050
    • MECS Cottbus GmbH
  • Cottbus, Germany, 03042
    • Carl-Thiem-Klinikum gGmbH
  • Cottbus, Germany, 03050
    • Ambulantes Zentrum für Lungenkrankheiten&Schlafmedizin
  • Dortmund, Germany, 44135
    • Praxis Dr. Hecker
  • Dortmund, Germany, 44137
    • Kardiologische Praxis Dr. Golling
  • Dortmund, Germany, 44141
    • Clinical Trial Site Services
  • Dortmund, Germany, 44141
    • Kardiologische Praxis Dr. Wetzel
  • Dortmund, Germany, 44147
    • Kardiologische Praxis Dr. Lodde
  • Dortmund, Germany, 44263
    • Kardiologische Praxis Dr. Dröse
  • Dresden, Germany, 01099
    • Facharztzentrum Dresden-Neustadt GbR
  • Dresden, Germany, 01277
    • Praxis Dr. Hohensee
  • Dresden, Germany, 01307
    • Herzzentrum Universität Dresden
  • Dresden, Germany, 01219
    • Gemeinschaftspraxis Dres. Schmidt/Gronke
  • Düsseldorf, Germany, 40217
    • Evangelisches Krankenhaus
  • Düsseldorf, Germany, 40212
    • goMedus Gesundheitszentrum
  • Düsseldorf, Germany, 40215
    • Kardiologische Praxis Dr. Horowitz
  • Düsseldorf, Germany, 40237
    • Kardiologische Praxis Dr. Raff
  • Düsseldorf, Germany, 40489
    • Florence-Nightingale Krankenhaus
  • Düsseldorf, Germany, 40545
    • Kardiologie Oberkassel
  • Düsseldorf, Germany, 40597
    • Gemeinschaftspraxis PD. Dr. Lankisch
  • Emmendingen, Germany, 79312
    • Fachärzte für Innere Medizin Dres Ritter, Richter, Mehrer, Kahl
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt-Kardiologie
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt-Schlafmedizin
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Essen, Germany, 45239
    • Ruhrlandklinik Essen
  • Essen, Germany, 45138
    • Elisabeth-Krankenhaus Essen
  • Essen, Germany, 45122
    • Westdeutsches Herzzentrum, Universitätsklinikum Essen
  • Essen, Germany, 45131
    • Kardiologische Praxis Dr. Cord Müller
  • Essen, Germany, 45131
    • Schwerpunktpraxis Kardiologie Drs. Ophoff/Fritzsch
  • Essen, Germany, 45134
    • Kardiologische Praxis Prof. Winter
  • Essen, Germany, 45136
    • Kardiologie Praxis Dr. Bonnekamp
  • Essen, Germany, 45136
    • Praxis Dr. Tekiyeh
  • Essen, Germany, 45276
    • Praxis Dr. Rau
  • Essen, Germany, 45359
    • Kath. Kliniken Essen / Philippusstift
  • Flonheim, Germany, 55237
    • Gemeinschaftspraxis Dres. Guckenbiehl
  • Forst, Germany, 03149
    • Kardiologische Praxis Dr. Kruse
  • Frankfurt, Germany, 60389
    • CardioVasculäres Centrum Frankfurt
  • Frechen, Germany, 50226
    • Praxis Dr. Diedrichs
  • Freiburg im Breisgau, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Gladbeck, Germany, 45964
    • Gemeinschaftspraxis Dres. Böhmeke/Schmidt
  • Günzburg, Germany, 89312
    • Kardiologische Praxis Dr. Hug
  • Gütersloh, Germany, 33334
    • Kardiologische Praxis Gütersloh
  • Hagen, Germany, 58095
    • Gemeinschaftspraxis Dres Leischik/Littwitz
  • Hagen, Germany, 58095
    • Kardiologische Praxis Dr. Arens
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Hamburg, Germany, 22291
    • Asklepios Klinik Barmbek
  • Hamburg, Germany, 20095
    • Gemeinschaftspraxis Dres. Subin/Lutter
  • Hamburg, Germany, 22399
    • Internistenpraxis Alstertal Hamburg
  • Hannover, Germany, 30159
    • Kardiologische Praxis Dr. Cierpka
  • Hannover, Germany, 30449
    • Praxis Dr. Hötte
  • Hannover, Germany, 30449
    • Siloah Krankenhaus
  • Hannover, Germany, 30559
    • Kardiologische Praxis Dr. Hartung
  • Hannover, Germany, 30625
    • MH Hannover
  • Hannover, Germany, 30659
    • Klinikum Hannover Oststadt-Heidehaus
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • Heidelberg, Germany, 69115
    • Praxis Dr. Durak
  • Hemer, Germany, 58675
    • Lungenklinik Hemer
  • Herne, Germany, 44623
    • Kardiologische Praxis Dr. Furche
  • Herne, Germany, 44629
    • Gemeinschaftspraxis Dr. Bruch
  • Herne, Germany, 44649
    • Kardiologische Praxis Dr. Schlichting
  • Herne, Germany, 44651
    • Augusta-Kranken-Anstalt gGmbH Thoraxzentrum Ruhrgebiet
  • Herten, Germany, 45699
    • St. Elisabeth-Hospital Herten gGmbH
  • Immenhausen, Germany, 34376
    • Lungenfachklinik Immenhausen
  • Karlstadt, Germany, 97753
    • Gemeinschaftspraxis Dres. Dobler/Turin
  • Kassel, Germany, 34121
    • Ambulantes Herzzentrum Kassel
  • Kempen, Germany, 47906
    • Kardiologische Praxis Dr. Siegfried Frickel
  • Krefeld, Germany, 47805
    • Helios Klinikum Krefeld
  • Krefeld, Germany, 47799
    • Praxis Dr. Krater
  • Köln, Germany, 50733
    • St.-Vinzenz Hospital
  • Köln, Germany, 50737
    • Kardiologische Praxis Dr. Fritsch
  • Köln, Germany, 50937
    • Prof. Franzen Institut
  • Köln, Germany, 51065
    • Praxis Dr. Anselm Bäumer
  • Köln, Germany, 51105
    • Gemeinschaftspraxis Dres. Gysan/Heinzler/May
  • Köln, Germany, 50931
    • Malteser Krankenhaus St.Hildegardis
  • Königs Wusterhausen, Germany, 15711
    • Klinikum Dahme-Spreewald GmbH
  • Leipzig, Germany, 04289
    • Universitätsklinikum Leipzig-Herzzentrum
  • Leisnig, Germany, 04703
    • Helios Krankenhaus Leisnig
  • Lengerich, Germany, 49525
    • Gemeinschaftspraxis Dr. Hilgedieck/Sava
  • Lindlar, Germany, 51784
    • Kardiologische Praxis Dr. Faber
  • Lingen, Germany, 49808
    • Ärztezentrum Holthausen-Biene
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein Campus Lübeck-Kardiologie
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein Campus Lübeck-Schlaflabor
  • Mainz, Germany, 55101
    • Klinikum der Johannes Gutenberg-Universität Mainz
  • Mainz, Germany, 55116
    • Cardiopraxis Ingelheim
  • Mannheim, Germany, 68161
    • Gemeinschaftspraxis Dres. Heifer/Loster/Schernus
  • Mannheim, Germany, 68161
    • Gemeinschaftspraxis für Herz & Gefäße
  • Mannheim, Germany, 68167
    • Universitätsklinik Mannheim-Kardiologie
  • Mannheim, Germany, 68305
    • Gemeinschaftspraxis Dres. Brandt / Jakobs
  • Mannheim, Germany, 68135
    • Universitätsklinikum Mannheim-Schlafmedizin
  • Marburg, Germany, 35043
    • Universitätsklinikum Gießen/Marburg Standort Marburg-Kardiologie
  • Marburg, Germany, 35033
    • Universitätsklinikum Gießen / Marburg, Standort Marburg-Schlafmedizin
  • Meissen, Germany, 01662
    • Praxis Dr. Schnabel
  • Memmingen, Germany, 87700
    • Gemeinschaftspraxis Dr. Jocham
  • 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, 80634
    • Kardiologie am Rotkreuzplatz
  • München, Germany, 80799
    • Gemeinschaftspraxis Dres. Wauer / Windstetter
  • München, Germany, 80809
    • Kardiologische Praxis Dr. Herholz
  • München, Germany, 81667
    • Praxis Dres. Böhme/Linke
  • München, Germany, 80634
    • Lungenärzte am Rotkreuzplatz
  • München, Germany, 81375
    • Klinik Augustinum München
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
  • Münster, Germany, 29633
    • Kardiologische Praxis Dr. Muradi
  • Münster, Germany, 48151
    • Praxis für Kardiologie Dr. med. Hewing
  • Neuss, Germany, 41464
    • Lukaskrankenhaus GmbH
  • Nienburg, Germany, 31582
    • Kardiologische Praxis Nienburg
  • Nürnberg, Germany, 90419
    • Klinikum Nürnberg Nord
  • Nürnberg, Germany, 90471
    • Klinikum Nürnberg Süd
  • Ochtrup, Germany, 48607
    • Kardiologische Praxis Dr. Gumbrecht
  • Radebeul, Germany, 01445
    • Kardiologische Praxis Dr. Wiethölter
  • Ratingen, Germany, 40878
    • Praxis für Kardiologie Ratingen
  • Ratingen, Germany, 40885
    • Praxis Dr. Fröhlich
  • Ratzeburg, Germany, 23909
    • DRK Krankenhaus Mölln-Ratzeburg
  • Ravensburg, Germany, 88212
    • Ambulantes Cardiovaskuläres Centrum
  • Recklinghausen, Germany, 45657
    • Gemeinschaftspraxis Dr. Weber/Dr. Feja
  • Recklinghausen, Germany, 45657
    • Knappschafts-Krankenhaus Recklinghausen
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
  • Reinbek, Germany, 21465
    • Praxis Dr. Hein
  • Reinbek, Germany, 21465
    • Krankenhaus Reinbek St. Adolf-Stift
  • Rheine, Germany, 48429
    • Praxis Dr. Nebel
  • Rheine, Germany, 48431
    • Praxis Dr. Kestermann
  • Schwerte, Germany, 58239
    • Kardiologische Praxis Dr. Heinze
  • Schönefeld, Germany, 12529
    • Praxis Dr. Ebeling
  • Soest, Germany, 59494
    • Praxisgemeinschaft Cardio-Soest
  • Sonneberg, Germany, 96515
    • Facharztzentrum Sonneberg
  • Stollberg, Germany, 09366
    • Kreiskrankenhaus Stollberg GmbH
  • Uelzen, Germany, 29525
    • Klinikum Uelzen GmbH
  • Ulm, Germany, 89077
    • Herzklinik Ulm Dr. Haerer und Partner
  • Ulm, Germany, 89081
    • Zentrum für Innere Medizin Uni Ulm
  • Unna, Germany, 59423
    • Katharinen Hospital Unna
  • Viersen, Germany, 41747
    • Kardiologische Praxis Dr. Burkhard-Meier
  • Waldkraiburg, Germany, 84478
    • Praxis Dr. Gerritsen
  • Wangen, Germany, 88239
    • Fachkliniken Wangen
  • Weißenhorn, Germany, 89264
    • Stiftungsklinik Weißenhorn
  • Witten, Germany, 58452
    • Kardiologische Praxis Dr. Vrettos
  • Worms, Germany, 67547
    • Kardiologische Praxis Dr. Rudolf/ Dr. Bernhardt
  • Würzburg, Germany, 97080
    • Universitatsklinikum Wurzburg
  • Würzburg, Germany, 97074
    • Missionsärztliche Klinik Würzburg
  • Zweibrücken, Germany, 66482
    • Evangel. Khs Zweibrücken
  • Rheinland-Pfalz
    • Ingelheim Am Rhein, Rheinland-Pfalz, Germany, 55218
      • Cardiopraxis Ingelheim
• Netherlands
  • Groningen, Netherlands, 9700
    • University Medical Center Groningen
• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital, Rikshospitalet
  • Oslo, Norway, 0407
    • Ullevål University Hospital
  • Stavanger, Norway, 4011
    • Stavanger AS
• Sweden
  • Göteborg, Sweden, 41345
    • Sahlgrenska University Hospital / Östra
  • Göteborg, Sweden, U/6 85
    • Sahlgrenska University Hospital / Östra
  • Jönköping, Sweden, 55316
    • Specialistläkarmottagning Residenset AB
  • Lidköping, Sweden, 53185
    • Skaraborgs Hospital
  • Linköping, Sweden, 58185
    • Linköping University Hospital
• Switzerland
  • Lugano, Switzerland, 6900
    • Cardiocentro Ticino
  • Lugano, Switzerland, 6903
    • Ospedale Regionale di Lugano
• United Kingdom
  • Chesterfield, United Kingdom, Calow S44 5DX
    • Chesterfield Royal Hospital
  • London, United Kingdom, SW36NP
    • Brompton Hospital
  • Newcastle, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Taunton, United Kingdom, TA1 5DA
    • Musgrove Park Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • Royal Wolverhampton Hospitals NHS Trust
  • East Yorkshire
    • Cottingham, East Yorkshire, United Kingdom, HU165JQ
      • Castle Hill 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

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 (angiotensin converting Enzyme) inhibitors/ ARB (angiotensin receptor blocker) 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 (TM)/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 (chronic obstructive pulmonary disease) 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 (cardiac resynchronisation therapy)-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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment Group; treatment with Adaptive Servoventilation (Europe: AutoSet CS (USA: VPAP (Variable Positive Airway Pressure) Adapt SV)) + standard medical therapy according to applicable guidelines (ESC, ACC/AHA)	Device: Europe: AutoSet CS (USA: VPAP Adapt SV); At least 3 hours average daily usage time
No Intervention: Control Group; standard medical therapy according to applicable guidelines (ESC, ACC/AHA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All Cause Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure	time to first event, assessed for up to 70 weeks
Cardiovascular Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure	time to first event, assessed for up to 70 weeks
All Cause Mortality or All Cause Unplanned Hospitalisation/Prolongation of Hospitalisation	time to first event, assessed for up to 70 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death From Any Cause		the last follow up or at the last available observation within Follow Up (FU), assessed for up to 70 weeks
Non-cardiovascular Death		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Cardiovascular Death		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Unplanned Hospitalisation/Prolongation of Hospitalisation Due to Worsening of Heart Failure		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Unplanned Hospitalisation/Prolongation of Hospitalisation for Other Reasons or Death		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Adequate Shock in Patients With ICD (Evaluation of Appropriateness Will Also be Made by the Endpoint Review Committee, ERC), Long-Term Atrial Defibrillator Insertion or Cardiovascular Death		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
First Survived Resuscitation for Any Reason (Evaluation Will Also be Made by the ERC)		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
First Survived Resuscitation of Sudden Cardiac Arrest (Evaluation Will Also be Made by the ERC)		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Age Baseline		1 x at Baseline
Body Weight Baseline		1 x at baseline
Body Mass Index (BMI) Baseline		1 x baseline
Left Ventricular Ejection Fraction at Baseline		1x at baseline
Blood Pressure Systolic Baseline		1 x at baseline
Blood Pressure Diastolic Baseline		1 x at baseline
Hemoglobine Baseline		1 x at baseline
Creatinine Baseline		1 x at baseline
Glomerular Filtration Rate Baseline		1 x at baseline
6-Min Walk Distance		1 x at baseline
Epworth Sleepiness Scale (ESS)	Measure Description: ESS is a self-administered questionnaire. It contains 8 questions. Questions are rated on a 4-point Likert scale (0-3); 0= would never doze, 3=high Chance of dozing. Range of scores 0-24. Global score= sum of all item scores. Copyright (c)MW Johns	1 x at baseline
Apnoea-Hypopnea-Index (AHI) at Baseline	Measure Description: The AHI is an index to describe the severity of Sleep Apnea. Apnea is cessation of breathing during sleep. Hypopnea is diminished breathing during sleep. The number of Apneas and Hypopneas are added up and divided by hours of sleep (Apneas + Hypopneas per hour). An AHI ranging from 5-15 describes mild Sleep Apnea. AHI 15-30 describes moderate Sleep Apnea. AHI >30 describes severe Sleep Apnea.	1 x at baseline
Central Apnoea Index/Total AHI	Measure Description: Central apneas are partial or complete cessations of airflow caused by reduced or stopped neural Stimulation of the breathing muscles. For comparison: In obstructive apneas are caused by blocked airways that shut off the air although the breathing Stimulus is working.	1 x at baseline
Central AHI/Total AHI at Baseline		1 x at baseline
Oxygen Desaturation Index (ODI) at Baseline	Number of oxygen desaturations per hour at baseline	1 x at baseline
Oxygen Saturation Baseline		1 x at baseline
Time With Oxygen Saturation Below 90%		1 x at baseline
Time Until Unplanned Hospitalisation/Prolongation of Hospitalisation for Cardiovascular Cause or Cardiovascular Death/ Time Frame		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Percent of Follow up Days Which Patient Survives and is Not Hospitalized/Hospital Stay is Not Prolonged for Cardiovascular Cause		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Changes in NYHA Classification as Compared to Baseline		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Changes in QoL (Minnesota) as Compared to Baseline		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Changes in Renal Function (Based on Serum Creatinine) as Compared to Baseline		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Changes in Six Minute Walking Distance (6MWD) as Compared to Baseline		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Changes of AHI and Oxygen Desaturation Index Compared to Baseline		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
AHI Below 10 Per Hour at Twelve Months and ODI Below 5 Per Hour at Twelve Months		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Atrial Fibrillation at Follow-up Visits		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Number and Cost of Hospitalisations (With Tariff/DRG, Diagnoses and Procedures for Calculating DRG or Length of Stay and Level of Care Provided)		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Difference in Utilities / QoL (Minnesota and EQ5D) Compared to Control Arm		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Difference in Cost of Resources Consumed		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Incremental Cost-efficacy Ratio		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Incremental Cost-utility Ratio		the last follow up or at the last available observation within FU, assessed for up to 70 weeks

Collaborators and Investigators

• Sponsor: ResMed
• Collaborators: CRI-The Clinical Research Institute GmbH
• Investigators: Principal Investigator: Helmut Teschler, Prof., Universitätsklinikum Essen; Principal Investigator: Martin Cowie, Prof., National Heart and Lung Institute (NHLI) Brompton Hospital, London

Publications and helpful links

General Publications

• Cowie MR, Wegscheider K, Teschler H. Adaptive Servo-Ventilation for Central Sleep Apnea in Heart Failure. N Engl J Med. 2016 Feb 18;374(7):690-1. doi: 10.1056/NEJMc1515007. No abstract available.
• Eulenburg C, Wegscheider K, Woehrle H, Angermann C, d'Ortho MP, Erdmann E, Levy P, Simonds AK, Somers VK, Zannad F, Teschler H, Cowie MR. Mechanisms underlying increased mortality risk in patients with heart failure and reduced ejection fraction randomly assigned to adaptive servoventilation in the SERVE-HF study: results of a secondary multistate modelling analysis. Lancet Respir Med. 2016 Nov;4(11):873-881. doi: 10.1016/S2213-2600(16)30244-2. Epub 2016 Aug 31.
• Woehrle H, Cowie MR, Eulenburg C, Suling A, Angermann C, d'Ortho MP, Erdmann E, Levy P, Simonds AK, Somers VK, Zannad F, Teschler H, Wegscheider K. Adaptive servo ventilation for central sleep apnoea in heart failure: SERVE-HF on-treatment analysis. Eur Respir J. 2017 Aug 31;50(2):1601692. doi: 10.1183/13993003.01692-2016. Print 2017 Aug.
• Shafazand S, Badr MS. Adaptive Servo-Ventilation and Central Apnea Associated with Systolic Heart Failure. J Clin Sleep Med. 2016 Jan;12(1):147-50. doi: 10.5664/jcsm.5420. No abstract available.
• Cowie MR, Woehrle H, Wegscheider K, Angermann C, d'Ortho MP, Erdmann E, Levy P, Simonds AK, Somers VK, Zannad F, Teschler H. Adaptive Servo-Ventilation for Central Sleep Apnea in Systolic Heart Failure. N Engl J Med. 2015 Sep 17;373(12):1095-105. doi: 10.1056/NEJMoa1506459. Epub 2015 Sep 1.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: February 14, 2008
• First Submitted That Met QC Criteria: August 11, 2008
• First Posted (Estimate): August 13, 2008

Study Record Updates

• Last Update Posted (Actual): May 12, 2020
• Last Update Submitted That Met QC Criteria: April 29, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: sleep apnea; left ventricular systolic dysfunction; heart failure (HF); sleep disordered breathing (SDB)
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Nervous System Diseases; Respiratory Tract Diseases; Apnea; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Heart Failure; Sleep Apnea Syndromes; Respiratory Aspiration; Sleep Apnea, Central
• Other Study ID Numbers: 01 (Miami VAHS); ISRCTN19572887 (Other Identifier: International Standard Randomised Controlled Trials)