Treatment of Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients With Heart Failure

Heart Failure Clinical Trial

— Serve-HF  

Official title:

Treatment of Sleep-Disordered Breathing With Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00733343
• Other study ID #: 01
• Secondary ID: ISRCTN19572887
• Status: Completed
• Phase: N/A
• Start date: February 2008
• Est. completion date: June 2015

Study information

• Verified date: April 2020
• Source: ResMed
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1325
• Est. completion date: June 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Respiratory Aspiration
• Sleep Apnea Syndromes
• Sleep Apnea, Central
• Sleep Disordered Breathing

Intervention

Device:
• Europe: AutoSet CS (USA: VPAP Adapt SV)
At least 3 hours average daily usage time

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
Czechia	St. Anne's University Hospital BRNO	Brno
Denmark	Århus Universitets Hospital	Århus C
Denmark	Århus Universitets Hospital Skejby	Århus N
Denmark	Bispebjerg Hospital	Copenhagen
Denmark	Rigshospitalet	Copenhagen
Denmark	Dansk Center For Søvnmedicin	Glostrup
Denmark	Glostrup Hospital	Glostrup
Finland	Helsinki University Hospital	Helsinki
Finland	Tampere University Hospital, Pirkanmaa sairaanhoitopiiri	Tampere
Finland	Unesta Research Centre	Tampere
France	Cardiologist Dr. Papola	Amneville
France	CHU Angers	Angers
France	Centre Hospitalier d'Antibes Juan-les-Pins	Antibes
France	Hopital Prive d'Antony	Antony
France	CH Belfort	Belfort
France	CH de Besancon	Besancon
France	Centre Hospitalier de Béziers	Beziers
France	CHU Bordeaux, Hopital Pellegrin	Bordeaux
France	Clinique du Tondu	Bordeaux
France	Hôpital St. André	Bordeaux
France	Praxis Cardiologique Dr. Puel	Bordeaux
France	Praxis Cardiologique Dr. Wickers	Bordeaux
France	CHU de Caen	Caen Cedex
France	Centre Hospitalier de Cannes	Cannes
France	Hopital Henri Mondor	Creteil
France	Hôpital Sud	Echirolles
France	CH de Forbach, Hospitalor, Hopital Marie Madeleine-Pneumology	Forbach
France	CH de Forbach-Cardiology	Forbach
France	CHU Grenoble, Hopital Michallon	Grenoble
France	Clinique Mutualiste des Eaux Claires	Grenoble
France	CH Haguenau	Haguenau
France	Clinique de L'Union	L'Union
France	CHU Lille- Hopital Cardiologique	Lille
France	CHU Lille-Sleep medicine	Lille
France	Polyclinique La Louviere	Lille
France	Hospices Civils de Lyon, Hopital de la Croix-Rousse	Lyon
France	CHR Metz, Hôpital de Bon-Secours	Metz
France	CH Montbeliard	Montbeliard
France	CHU de Montpellier	Montpellier
France	CH Intercommunal André Grégoire	Montreuil
France	CH de Mulhouse, Hopital Emile Muller	Mulhouse
France	Clinique les Fleurs	Ollioules
France	CHU Tenon	Paris
France	Hôpital Bichat	Paris
France	CHU de Bordeaux, Hopital Haut Leveque	Pessac
France	CHU de Poitiers	Poitiers
France	Cabinet de cardiologie	Pont-à-mousson
France	CH Rene Dubos	Pontoise
France	Polyclinique Saint-Laurent	Rennes
France	CHU de Rouen, Hopital de Bois Guillaume	Rouen
France	CH Lemire - St Avold	Saint Avold
France	Clinique des Trois Frontières	Saint Louis
France	CHU de Saint-Etienne, Hopital Nord	Saint- Etienne
France	CH de St Dié des Vosges	St Dié des Vosges
France	CHU Toulouse, Hopital de Rangueil	Toulouse
France	CHU Toulouse, Hopital Larrey	Toulouse
France	CH Trouville	Trouville
France	CHU de Nancy, Hopital Brabois	Vandoeuvre les Nancy
France	Ch St. Nicolas	Verdun
Germany	Praxis Dr. Frieske	Aachen
Germany	Universitätsklinikum Aachen	Aachen
Germany	DRK Krankenhaus	Alzey
Germany	Gemeinschaftspraxis Weiß / Dr. Heesing	Arnsberg
Germany	Zentralklinikum Bad Berka	Bad Berka
Germany	Herzzentrum Bad Krozingen	Bad Krozingen
Germany	Klinik Lazariterhof	Bad Krozingen
Germany	Schlaflabor Breisgau	Bad Krozingen
Germany	Praxis Dr. Bauer	Bad Mergentheim
Germany	Herz- und Diabeteszentrum NRW	Bad Oeynhausen
Germany	Oberlausitz-Kliniken gGmbH	Bautzen
Germany	Kardiologie Brühl	Bergheim
Germany	Kardiopraxis Rheinberg	Bergisch Gladbach
Germany	Charité Campus Mitte - Kardiologie	Berlin
Germany	Charité Campus Mitte CCM- Schlafmedizinisches Zentrum	Berlin
Germany	Charité Campus Virchow Klinikum	Berlin
Germany	Evangelische Lungenfachklinik Buch	Berlin
Germany	Gemeinschaftspraxis Groß-Ziethener Chaussee	Berlin
Germany	Jüdisches Krankenhaus Berlin	Berlin
Germany	POLIKUM Friedenau	Berlin
Germany	Praxis Westend	Berlin
Germany	Unfallkrankenhaus Berlin	Berlin
Germany	Herzzentrum Brandenburg	Bernau
Germany	Praxis für Lunge, Herz und Schlaf	Bielefeld
Germany	Augusta Krankenanstalten Bochum	Bochum
Germany	Kardiologie Gemeinschaftspraxis Dres Tenholt&Metzger&Dexling	Bochum
Germany	Kardiologie Kemnade	Bochum
Germany	Kardiologische Praxis Dr. Staubach	Bochum
Germany	St.-Josephs-Hospital	Bochum
Germany	Universitätsklinikum Bergmannsheil	Bochum
Germany	Kardiologische Praxis Marschner	Bonn
Germany	Universitätsklinikum Bonn	Bonn
Germany	Helios Klinikum Borna	Borna
Germany	Gemeinschaftspraxis Kardiologie	Bottrop
Germany	Klinikum Bremen Ost	Bremen
Germany	Kardiologie Brühl	Brühl
Germany	Mediclin Rehazentrum Spreewald	Burg
Germany	Gemeinschaftspraxis Kardiologie Dr. Becker	Castrop-Rauxel
Germany	Kardiologische Praxis Dr. Isbruch	Castrop-Rauxel
Germany	MVZ am Küchwald	Chemnitz
Germany	Klinikum Coburg GmbH	Coburg
Germany	Fachkrankenhaus Coswig	Coswig
Germany	Ambulantes Zentrum für Lungenkrankheiten&Schlafmedizin	Cottbus
Germany	Carl-Thiem-Klinikum gGmbH	Cottbus
Germany	MECS Cottbus GmbH	Cottbus
Germany	Clinical Trial Site Services	Dortmund
Germany	Kardiologische Praxis Dr. Dröse	Dortmund
Germany	Kardiologische Praxis Dr. Golling	Dortmund
Germany	Kardiologische Praxis Dr. Lodde	Dortmund
Germany	Kardiologische Praxis Dr. Wetzel	Dortmund
Germany	Praxis Dr. Hecker	Dortmund
Germany	Facharztzentrum Dresden-Neustadt GbR	Dresden
Germany	Gemeinschaftspraxis Dres. Schmidt/Gronke	Dresden
Germany	Herzzentrum Universität Dresden	Dresden
Germany	Praxis Dr. Hohensee	Dresden
Germany	Evangelisches Krankenhaus	Düsseldorf
Germany	Florence-Nightingale Krankenhaus	Düsseldorf
Germany	Gemeinschaftspraxis PD. Dr. Lankisch	Düsseldorf
Germany	goMedus Gesundheitszentrum	Düsseldorf
Germany	Kardiologie Oberkassel	Düsseldorf
Germany	Kardiologische Praxis Dr. Horowitz	Düsseldorf
Germany	Kardiologische Praxis Dr. Raff	Düsseldorf
Germany	Fachärzte für Innere Medizin Dres Ritter, Richter, Mehrer, Kahl	Emmendingen
Germany	Helios Klinikum Erfurt-Kardiologie	Erfurt
Germany	Helios Klinikum Erfurt-Schlafmedizin	Erfurt
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Elisabeth-Krankenhaus Essen	Essen
Germany	Kardiologie Praxis Dr. Bonnekamp	Essen
Germany	Kardiologische Praxis Dr. Cord Müller	Essen
Germany	Kardiologische Praxis Prof. Winter	Essen
Germany	Kath. Kliniken Essen / Philippusstift	Essen
Germany	Praxis Dr. Rau	Essen
Germany	Praxis Dr. Tekiyeh	Essen
Germany	Ruhrlandklinik Essen	Essen
Germany	Schwerpunktpraxis Kardiologie Drs. Ophoff/Fritzsch	Essen
Germany	Westdeutsches Herzzentrum, Universitätsklinikum Essen	Essen
Germany	Gemeinschaftspraxis Dres. Guckenbiehl	Flonheim
Germany	Kardiologische Praxis Dr. Kruse	Forst
Germany	CardioVasculäres Centrum Frankfurt	Frankfurt
Germany	Praxis Dr. Diedrichs	Frechen
Germany	Universitaetsklinikum Freiburg	Freiburg im Breisgau
Germany	Gemeinschaftspraxis Dres. Böhmeke/Schmidt	Gladbeck
Germany	Kardiologische Praxis Dr. Hug	Günzburg
Germany	Kardiologische Praxis Gütersloh	Gütersloh
Germany	Gemeinschaftspraxis Dres Leischik/Littwitz	Hagen
Germany	Kardiologische Praxis Dr. Arens	Hagen
Germany	Asklepios Klinik Barmbek	Hamburg
Germany	Gemeinschaftspraxis Dres. Subin/Lutter	Hamburg
Germany	Internistenpraxis Alstertal Hamburg	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Kardiologische Praxis Dr. Cierpka	Hannover
Germany	Kardiologische Praxis Dr. Hartung	Hannover
Germany	Klinikum Hannover Oststadt-Heidehaus	Hannover
Germany	MH Hannover	Hannover
Germany	Praxis Dr. Hötte	Hannover
Germany	Siloah Krankenhaus	Hannover
Germany	Praxis Dr. Durak	Heidelberg
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Lungenklinik Hemer	Hemer
Germany	Augusta-Kranken-Anstalt gGmbH Thoraxzentrum Ruhrgebiet	Herne
Germany	Gemeinschaftspraxis Dr. Bruch	Herne
Germany	Kardiologische Praxis Dr. Furche	Herne
Germany	Kardiologische Praxis Dr. Schlichting	Herne
Germany	St. Elisabeth-Hospital Herten gGmbH	Herten
Germany	Lungenfachklinik Immenhausen	Immenhausen
Germany	Cardiopraxis Ingelheim	Ingelheim Am Rhein	Rheinland-Pfalz
Germany	Gemeinschaftspraxis Dres. Dobler/Turin	Karlstadt
Germany	Ambulantes Herzzentrum Kassel	Kassel
Germany	Kardiologische Praxis Dr. Siegfried Frickel	Kempen
Germany	Gemeinschaftspraxis Dres. Gysan/Heinzler/May	Köln
Germany	Kardiologische Praxis Dr. Fritsch	Köln
Germany	Malteser Krankenhaus St.Hildegardis	Köln
Germany	Praxis Dr. Anselm Bäumer	Köln
Germany	Prof. Franzen Institut	Köln
Germany	St.-Vinzenz Hospital	Köln
Germany	Klinikum Dahme-Spreewald GmbH	Königs Wusterhausen
Germany	Helios Klinikum Krefeld	Krefeld
Germany	Praxis Dr. Krater	Krefeld
Germany	Universitätsklinikum Leipzig-Herzzentrum	Leipzig
Germany	Helios Krankenhaus Leisnig	Leisnig
Germany	Gemeinschaftspraxis Dr. Hilgedieck/Sava	Lengerich
Germany	Kardiologische Praxis Dr. Faber	Lindlar
Germany	Ärztezentrum Holthausen-Biene	Lingen
Germany	Universitätsklinikum Schleswig-Holstein Campus Lübeck-Kardiologie	Lübeck
Germany	Universitätsklinikum Schleswig-Holstein Campus Lübeck-Schlaflabor	Lübeck
Germany	Cardiopraxis Ingelheim	Mainz
Germany	Klinikum der Johannes Gutenberg-Universität Mainz	Mainz
Germany	Gemeinschaftspraxis Dres. Brandt / Jakobs	Mannheim
Germany	Gemeinschaftspraxis Dres. Heifer/Loster/Schernus	Mannheim
Germany	Gemeinschaftspraxis für Herz & Gefäße	Mannheim
Germany	Universitätsklinik Mannheim-Kardiologie	Mannheim
Germany	Universitätsklinikum Mannheim-Schlafmedizin	Mannheim
Germany	Universitätsklinikum Gießen / Marburg, Standort Marburg-Schlafmedizin	Marburg
Germany	Universitätsklinikum Gießen/Marburg Standort Marburg-Kardiologie	Marburg
Germany	Praxis Dr. Schnabel	Meissen
Germany	Gemeinschaftspraxis Dr. Jocham	Memmingen
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	Gemeinschaftspraxis Dres. Wauer / Windstetter	München
Germany	Kardiologie am Rotkreuzplatz	München
Germany	Kardiologische Praxis Dr. Herholz	München
Germany	Klinik Augustinum München	München
Germany	Lungenärzte am Rotkreuzplatz	München
Germany	Praxis Dres. Böhme/Linke	München
Germany	Kardiologische Praxis Dr. Muradi	Münster
Germany	Praxis für Kardiologie Dr. med. Hewing	Münster
Germany	Universitätsklinikum Münster	Münster
Germany	Lukaskrankenhaus GmbH	Neuss
Germany	Kardiologische Praxis Nienburg	Nienburg
Germany	Klinikum Nürnberg Nord	Nürnberg
Germany	Klinikum Nürnberg Süd	Nürnberg
Germany	Kardiologische Praxis Dr. Gumbrecht	Ochtrup
Germany	Kardiologische Praxis Dr. Wiethölter	Radebeul
Germany	Praxis Dr. Fröhlich	Ratingen
Germany	Praxis für Kardiologie Ratingen	Ratingen
Germany	DRK Krankenhaus Mölln-Ratzeburg	Ratzeburg
Germany	Ambulantes Cardiovaskuläres Centrum	Ravensburg
Germany	Gemeinschaftspraxis Dr. Weber/Dr. Feja	Recklinghausen
Germany	Knappschafts-Krankenhaus Recklinghausen	Recklinghausen
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Krankenhaus Reinbek St. Adolf-Stift	Reinbek
Germany	Praxis Dr. Hein	Reinbek
Germany	Praxis Dr. Kestermann	Rheine
Germany	Praxis Dr. Nebel	Rheine
Germany	Praxis Dr. Ebeling	Schönefeld
Germany	Kardiologische Praxis Dr. Heinze	Schwerte
Germany	Praxisgemeinschaft Cardio-Soest	Soest
Germany	Facharztzentrum Sonneberg	Sonneberg
Germany	Kreiskrankenhaus Stollberg GmbH	Stollberg
Germany	Klinikum Uelzen GmbH	Uelzen
Germany	Herzklinik Ulm Dr. Haerer und Partner	Ulm
Germany	Zentrum für Innere Medizin Uni Ulm	Ulm
Germany	Katharinen Hospital Unna	Unna
Germany	Kardiologische Praxis Dr. Burkhard-Meier	Viersen
Germany	Praxis Dr. Gerritsen	Waldkraiburg
Germany	Fachkliniken Wangen	Wangen
Germany	Stiftungsklinik Weißenhorn	Weißenhorn
Germany	Kardiologische Praxis Dr. Vrettos	Witten
Germany	Kardiologische Praxis Dr. Rudolf/ Dr. Bernhardt	Worms
Germany	Missionsärztliche Klinik Würzburg	Würzburg
Germany	Universitätsklinikum Würzburg	Würzburg
Germany	Evangel. Khs Zweibrücken	Zweibrücken
Netherlands	University Medical Center Groningen	Groningen
Norway	Oslo University Hospital, Rikshospitalet	Oslo
Norway	Ullevål University Hospital	Oslo
Norway	Stavanger AS	Stavanger
Sweden	Sahlgrenska University Hospital / Östra	Göteborg
Sweden	Sahlgrenska University Hospital / Östra	Göteborg
Sweden	Specialistläkarmottagning Residenset AB	Jönköping
Sweden	Skaraborgs Hospital	Lidköping
Sweden	Linköping University Hospital	Linköping
Switzerland	Cardiocentro Ticino	Lugano
Switzerland	Ospedale Regionale di Lugano	Lugano
United Kingdom	Chesterfield Royal Hospital	Chesterfield
United Kingdom	Castle Hill Hospital	Cottingham	East Yorkshire
United Kingdom	Brompton Hospital	London
United Kingdom	Freeman Hospital	Newcastle
United Kingdom	Musgrove Park Hospital	Taunton
United Kingdom	Royal Wolverhampton Hospitals NHS Trust	Wolverhampton

Sponsors (2)

Lead Sponsor	Collaborator
ResMed	CRI-The Clinical Research Institute

Countries where clinical trial is conducted

Australia,  Czechia,  Denmark,  Finland,  France,  Germany,  Netherlands,  Norway,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (3)

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. — View Citation

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 — View Citation

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 R — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All Cause Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure		time to first event, assessed for up to 70 weeks
Primary	Cardiovascular Mortality or Unplanned Hospitalisation/Prolongation of Hospitalisation for Worsening Heart Failure		time to first event, assessed for up to 70 weeks
Primary	All Cause Mortality or All Cause Unplanned Hospitalisation/Prolongation of Hospitalisation		time to first event, assessed for up to 70 weeks
Secondary	Death From Any Cause		the last follow up or at the last available observation within Follow Up (FU), assessed for up to 70 weeks
Secondary	Non-cardiovascular Death		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Secondary	Cardiovascular Death		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Age Baseline		1 x at Baseline
Secondary	Body Weight Baseline		1 x at baseline
Secondary	Body Mass Index (BMI) Baseline		1 x baseline
Secondary	Left Ventricular Ejection Fraction at Baseline		1x at baseline
Secondary	Blood Pressure Systolic Baseline		1 x at baseline
Secondary	Blood Pressure Diastolic Baseline		1 x at baseline
Secondary	Hemoglobine Baseline		1 x at baseline
Secondary	Creatinine Baseline		1 x at baseline
Secondary	Glomerular Filtration Rate Baseline		1 x at baseline
Secondary	6-Min Walk Distance		1 x at baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	Central AHI/Total AHI at Baseline		1 x at baseline
Secondary	Oxygen Desaturation Index (ODI) at Baseline	Number of oxygen desaturations per hour at baseline	1 x at baseline
Secondary	Oxygen Saturation Baseline		1 x at baseline
Secondary	Time With Oxygen Saturation Below 90%		1 x at baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Atrial Fibrillation at Follow-up Visits		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Secondary	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
Secondary	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
Secondary	Difference in Cost of Resources Consumed		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Secondary	Incremental Cost-efficacy Ratio		the last follow up or at the last available observation within FU, assessed for up to 70 weeks
Secondary	Incremental Cost-utility Ratio		the last follow up or at the last available observation within FU, assessed for up to 70 weeks