Effect of Adaptive Servo Ventilation (ASV) on Survival and Hospital Admissions in Heart Failure

Not Applicable

Terminated

• Conditions: Sleep Apnea; Heart Failure
• Interventions: Device: Adaptive Servo Ventilation

• Registration Number: NCT01128816
• Lead Sponsor: Toronto Rehabilitation Institute

Brief Summary

Sleep Apnea (SA) is a disorder that causes pauses in breathing during sleep that expose the heart to oxygen deprivation. It is common in patients with heart failure (HF) where it is associated with increased risk of hospitalizations and death. It is not known however whether treating SA reduces these risks. This study is looking at whether a respiratory device known as Adaptive Servo Ventilation (ASV) can reduce the rate of cardiovascular hospitalizations and death in subjects with HF and SA. Study subjects will randomly receive either their regular medications OR their regular medications plus ASV. They will be followed for approximately 5 years and information relevant to their health will be collected and compared.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-04-26
• Study Start: 2010-05
• Study First Submitted QC: 2010-05-21
• Study First Posted: 2010-05-24
• Primary Completion: 2022-03-31
• Study Completion: 2022-03-31
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-17
• Last Update Posted: 2022-11-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 732

Inclusion Criteria

• American Heart Association Stage B-D Heart failure due to ischemic, idiopathic or hypertensive causes, present for at least 3 months
• Left Ventricular Ejection Fraction ≤ 45 %
• Optimal medical therapy for heart failure
• No change in active cardiac medications for 2 weeks prior to randomization, beta-blockers must be started 3 months prior to randomization
• Sleep apnea with an AHI ≥ 15. Subjects with obstructive sleep apnea must also have an Epworth Sleepiness Scale score of ≤ 10 and no or mild daytime sleepiness
• Written informed consent

Exclusion Criteria

• Heart failure due to primary valvular heart disease
• Presence of moderate to severe mitral insufficiency due to intrinsic mitral valve disease
• Hypertrophic obstructive or restrictive or post partum cardiomyopathy
• Exercise capacity limited by class IV angina pectoris
• Acute MI, cardiac surgery, PCI, AICD, or CRT within 3 months of randomization
• Active myocarditis
• Planned AICD or CRT
• Presence of a left-ventricular assist device
• Transplanted heart or expected to receive a transplanted heart within the next 6 months
• Pregnancy
• Current use of ASV or CPAP or mandibular advancement device for treatment of sleep apnea or treated with any investigational therapy during the last 4 weeks (including approved therapies being used in unapproved indications)
• A clinical history that would interfere with the objectives of this study or that would in the investigator's opinion preclude safe conclusion of the study
• Any other medical, social, or geographical factor, which would make it unlikely that the patient will comply with the study procedures (e.g. alcohol abuse, lack of permanent residence, severe depression, disorientation, distant location, or history of non-compliance)
• Any contraindication to ASV therapy as detailed in the device provider manual

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard therapy for HF + ASV	Adaptive Servo Ventilation	Subjects will receive treatment with Adaptive Servo Ventilation in addition to optimal standard therapy for heart failure conforming to national guidelines, as determined by the referring cardiologist

Primary Outcome Measures

Name	Time	Method
The time to the composite outcome of death or first CV hospital admission or new onset atrial fibrillation/flutter requiring anti-coagulation but not hospitalization or delivery of an appropriate shock from an ICD not resulting in hospitalization.	The expected study follow-up period is five years	The study will end once 540 primary endpoints have occurred. The maximum follow-up period for all randomized subjects is 5 years.

Secondary Outcome Measures

Name	Time	Method
Time to death from any cause	The expected study follow-up period is 5 years	The study will end once 540 primary endpoints have occurred.
Number of cardiovascular hospitalizations per year of follow-up	The minimum time of follow-up is expected to be 2 years. The maximum time of follow-up is expected to be 5 years
Changes in left ventricular function	6 months from randomization	Changes in LV function will be assessed by echocardiography at baseline and at 6 months post randomization
Changes in Quality of life assessments	Assessments made at baseline, 1, 6, 12 and every 6 months thereafter	Minnesota living with Heart Failure Questionnaire and Epworth Sleepiness Scale will be used. Scores will be compared between the 2 groups.
Number of days alive not hospitalized	Time from randomization to censoring (death, primary event or end of study)	The number of days the patient is hospitalized are subtracted from the total number of days in the study from randomization. This number will be compared between the 2 groups.
Changes in plasma BNP levels	6 months from randomization	Changes in plasma NT-proBNP levels will be assessed at baseline and at 6 months post randomization
Changes in 6 minute walk test distance	6 months from randomization	Changes in the 6-minute walk distance between baseline and 6 months will be compared between the 2 groups
Percentage of patients with changes in stages of heart failure and functional class	Values obtained at study termination will be compared to those obtained at randomization	New York Heart Association classification and AHA/ACC Stages of Heart Failure will be assessed at each visit.
Changes in apnea/hypopnea index	1 month from randomization
Cardiac resynchronization therapy or defibrillator implantations	Average number of days until first cardiac resynchronization or first defibrillator implantation	The average number of days from randomization to the first occurrence of CRT or defibrillator implantation will be calculated and compared between each treatment arm.

Trial Locations

Locations (49)

University of Arizona/Southern Arizona VA Health Care System; 🇺🇸 Tucson, Arizona, United States

MetroHealth Medical Centre; 🇺🇸 Cleveland, Ohio, United States

CDEC Brasil - Centro de Desenvolvimento em Estudos Clínicos Brasil; 🇧🇷 São Paulo, SP, Brazil

Instituto do Coração do Hospital das Clínicas da FMUSP; 🇧🇷 São Paulo, SP, Brazil

St. Mary's General Hospital; 🇨🇦 Kitchener, Ontario, Canada

Kingston General Hospital Sleep Disorders Laboratory/Queen's University; 🇨🇦 Kingston, Ontario, Canada

McMaster University Medical Centre, Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada

Hôpital Hôtel-Dieu du CHUM; 🇨🇦 Montreal, Quebec, Canada

St. Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

London Health Sciences Centre - Victoria Hospital; 🇨🇦 London, Ontario, Canada

University of Ottawa-Ottawa Heart Institute; 🇨🇦 Ottawa, Ontario, Canada

University Health Network/TRI/Mount Sinai; 🇨🇦 Toronto, Ontario, Canada

McGill University Health Centre, Glen Site; 🇨🇦 Montreal, Quebec, Canada

Centre Hospitalier de Béziers; 🇫🇷 Béziers, France

Pole d'exploration de L' apnée du sommeil, Nouvelle Clinique Bel Air; 🇫🇷 Bordeaux, France

Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval; 🇨🇦 Quebec City, Quebec, Canada

Groupe Hospitalier Ambroise Paré, AP-HP; 🇫🇷 Boulogne-Billancourt, France

Hôpital Antoine Béclère, AP-HP; 🇫🇷 Clamart, France

Hôpital Bichat- Claude Bernard, AP-HP; 🇫🇷 Paris, France

Laboratoire d'Explorations Fonctionnelles Cardio-Respiratoires, Centre Hospitalier Universitaire de Grenoble; 🇫🇷 Grenoble, France

Groupe Hospitalier Pitié-Salpêtrière Charles Foix, AP-HP; 🇫🇷 Paris, France

Wissenschaftliches Institut Bethanien e.V.; 🇩🇪 Solingen, Germany

Saiseikai Futsukaichi Hospital; 🇯🇵 Fukuoka, Japan

Kyoto University Hospital; 🇯🇵 Kyoto, Japan

Toranomon Hospital; 🇯🇵 Tokyo, Japan

Juntendo University School of Medicine; 🇯🇵 Tokyo, Japan

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital San Pedro de Alcántara; 🇪🇸 Cáceres, Spain

Fundación Jiménez Diaz-CAPIO; 🇪🇸 Madrid, Spain

Hospital Arnau de Vilanova; 🇪🇸 Lleida, Spain

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Spain

Hospital Universitario Rio Hortega; 🇪🇸 Valladolid, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Hospital Universitario Txagorritxu; 🇪🇸 Vitoria, Álava, Spain

The Sleep Disorders Centre -Nuffield House, Guy's Hospital; 🇬🇧 London, United Kingdom

St. Boniface General Hospital; 🇨🇦 Winnipeg, Manitoba, Canada

ASST Franciacorta, Ospedale di Chiari; 🇮🇹 Chiari, BS, Italy

Prima Medicina-Spedali Civili; 🇮🇹 Brescia, Italy

Istituto Auxologico Italiano - Ospedale San Luca; 🇮🇹 Milano, Italy

Istituto Scientifico di Montescano, Istituti Clinici Scientifici Maugeri (ICS Maugeri); 🇮🇹 Pavia, Italy

Istituto Scientifico di Veruno, Istituti Clinici Scientifici Maugeri; 🇮🇹 Veruno, Italy

Instituto Dante Pazzanese de Cardiologia; 🇧🇷 São Paulo, SP, Brazil

Capital District Health Authority; 🇨🇦 Halifax, Nova Scotia, Canada

Vancouver General Hospital/UBC/VCHA; 🇨🇦 Vancouver, British Columbia, Canada

Pronto Socorro Cardiologico de Pernambuco; 🇧🇷 Recife, Pernambuco, Brazil

Glacier View Research Institute, Kalispell Regional Medical Center; 🇺🇸 Kalispell, Montana, United States

University of Regensburg; 🇩🇪 Regensburg, Bavaria, Germany

Tokyo Medical University Hospital; 🇯🇵 Tokyo, Japan