Clinical trial NCT01128816: Effect of Adaptive Servo Ventilation (ASV) on Survival and Hospital Admissions in Heart Failure
Official title: A Multi-Centre, Randomized Study to Assess the Effects of Adaptive Servo Ventilation (ASV) on Survival and Frequency of Hospital Admissions in Patients With Heart Failure (HF) and Sleep Apnea (SA)-The ADVENT-HF Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Sleep Apnea
Heart Failure
Keywords: obstructive sleep apnea
central sleep apnea
heart failure
congestive heart failure
adaptive servo ventilation
ASV
Lead sponsor: Toronto Rehabilitation Institute
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Philips Respironics
First posted: 2010-05-24
Enrollment: 732
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: The expected study follow-up period is five years
Secondary outcomes:
measure: Time to death from any cause
timeFrame: The expected study follow-up period is 5 years
measure: Number of cardiovascular hospitalizations per year of follow-up
timeFrame: The minimum time of follow-up is expected to be 2 years. The maximum time of follow-up is expected to be 5 years
measure: Number of days alive not hospitalized
timeFrame: Time from randomization to censoring (death, primary event or end of study)
measure: Changes in left ventricular function
timeFrame: 6 months from randomization
measure: Changes in plasma BNP levels
timeFrame: 6 months from randomization
measure: Cardiac resynchronization therapy or defibrillator implantations
timeFrame: Average number of days until first cardiac resynchronization or first defibrillator implantation
measure: Changes in 6 minute walk test distance
timeFrame: 6 months from randomization
measure: Percentage of patients with changes in stages of heart failure and functional class
timeFrame: Values obtained at study termination will be compared to those obtained at randomization
measure: Changes in apnea/hypopnea index
timeFrame: 1 month from randomization
measure: Changes in Quality of life assessments
timeFrame: Assessments made at baseline, 1, 6, 12 and every 6 months thereafter
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona/Southern Arizona VA Health Care System
state: Arizona
city: Kalispell
country: United States
facility: Glacier View Research Institute, Kalispell Regional Medical Center
state: Montana
city: Cleveland
country: United States
facility: MetroHealth Medical Centre
state: Ohio
city: Recife
country: Brazil
facility: Pronto Socorro Cardiologico de Pernambuco
state: Pernambuco
city: São Paulo
country: Brazil
facility: Instituto Dante Pazzanese de Cardiologia
state: SP
city: São Paulo
country: Brazil
facility: CDEC Brasil - Centro de Desenvolvimento em Estudos Clínicos Brasil
state: SP
city: São Paulo
country: Brazil
facility: Instituto do Coração do Hospital das Clínicas da FMUSP
state: SP
city: Vancouver
country: Canada
facility: Vancouver General Hospital/UBC/VCHA
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Halifax
country: Canada
facility: Capital District Health Authority
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University Medical Centre, Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital Sleep Disorders Laboratory/Queen's University
state: Ontario
city: Kitchener
country: Canada
facility: St. Mary's General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa-Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network/TRI/Mount Sinai
state: Ontario
city: Montreal
country: Canada
facility: Hôpital Hôtel-Dieu du CHUM
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre, Glen Site
state: Quebec
city: Quebec City
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval
state: Quebec
city: Bordeaux
country: France
facility: Pole d'exploration de L' apnée du sommeil, Nouvelle Clinique Bel Air
city: Boulogne-Billancourt
country: France
facility: Groupe Hospitalier Ambroise Paré, AP-HP
city: Béziers
country: France
facility: Centre Hospitalier de Béziers
city: Clamart
country: France
facility: Hôpital Antoine Béclère, AP-HP
city: Grenoble
country: France
facility: Laboratoire d'Explorations Fonctionnelles Cardio-Respiratoires, Centre Hospitalier Universitaire de Grenoble
city: Paris
country: France
facility: Hôpital Bichat- Claude Bernard, AP-HP
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière Charles Foix, AP-HP
city: Regensburg
country: Germany
facility: University of Regensburg
state: Bavaria
city: Solingen
country: Germany
facility: Wissenschaftliches Institut Bethanien e.V.
city: Chiari
country: Italy
facility: ASST Franciacorta, Ospedale di Chiari
state: BS
city: Brescia
country: Italy
facility: Prima Medicina-Spedali Civili
city: Milano
country: Italy
facility: Istituto Auxologico Italiano - Ospedale San Luca
city: Pavia
country: Italy
facility: Istituto Scientifico di Montescano, Istituti Clinici Scientifici Maugeri (ICS Maugeri)
city: Veruno
country: Italy
facility: Istituto Scientifico di Veruno, Istituti Clinici Scientifici Maugeri
city: Fukuoka
country: Japan
facility: Saiseikai Futsukaichi Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Tokyo
country: Japan
facility: Toranomon Hospital
city: Tokyo
country: Japan
facility: Juntendo University School of Medicine
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Fundación Jiménez Diaz-CAPIO
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Vitoria
country: Spain
facility: Hospital Universitario Txagorritxu
state: Álava
city: London
country: United Kingdom
facility: The Sleep Disorders Centre -Nuffield House, Guy's Hospital
Study officials:
affiliation: Toronto Rehabilitation Institute
name: Douglas Bradley, M.D.
role: STUDY_CHAIR
References:
citation: Perger E, Inami T, Lyons OD, Alshaer H, Smith S, Floras JS, Logan AG, Arzt M, Duran Cantolla J, Delgado D, Fitzpatrick M, Fleetham J, Kasai T, Kimoff RJ, Leung RST, Lorenzi Filho G, Mayer P, Mielniczuk L, Morrison DL, Parati G, Parthasarathy S, Redolfi S, Ryan CM, Series F, Tomlinson GA, Woo A, Bradley TD; ADVENT-HF Investigators. Distinct Patterns of Hyperpnea During Cheyne-Stokes Respiration: Implication for Cardiac Function in Patients With Heart Failure. J Clin Sleep Med. 2017 Nov 15;13(11):1235-1241. doi: 10.5664/jcsm.6788.