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

NCT01128816 | Terminated DMC

• 1 other identifier: ADVENT-HF trial
• Study Type: interventional
• Target: 732
• Locations: 9 countries
• Sites: 49

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.

Conditions

Sleep Apnea; Heart Failure

Keywords

obstructive sleep apnea; central sleep apnea; heart failure; congestive heart failure; adaptive servo ventilation; ASV

Outcome Measures

Primary Outcomes (1)

• 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 study will end once 540 primary endpoints have occurred. The maximum follow-up period for all randomized subjects is 5 years.

  The expected study follow-up period is five years

Secondary Outcomes (10)

• Time to death from any cause

  The expected study follow-up period is 5 years

• 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

• Number of days alive not hospitalized

  Time from randomization to censoring (death, primary event or end of study)

• Changes in left ventricular function

  6 months from randomization

• Changes in plasma BNP levels

  6 months from randomization

Study Arms (2)

Standard HF therapy

NO INTERVENTION

Subjects will receive optimal standard therapy for heart failure conforming to national guidelines as determined by the referring cardiologist

Standard therapy for HF + ASV

ACTIVE COMPARATOR

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

Device: Adaptive Servo Ventilation

Interventions

Adaptive Servo Ventilation DEVICE

BiPAP autoSV ADVANCED device worn nightly during sleep

Also known as: BiPAP autoSV ADVANCED, ASV, Respironics

Standard therapy for HF + ASV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Toronto Rehabilitation Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Philips Respironics: collaborator

Study Sites (49)

University of Arizona/Southern Arizona VA Health Care System

Tucson, Arizona, 85723, United States

Location

Glacier View Research Institute, Kalispell Regional Medical Center

Kalispell, Montana, 59901, United States

Location

MetroHealth Medical Centre

Cleveland, Ohio, 44109-1998, United States

Location

Pronto Socorro Cardiologico de Pernambuco

Recife, Pernambuco, CEP 50100-060, Brazil

Location

Instituto Dante Pazzanese de Cardiologia

São Paulo, São Paulo, CEP 04012-909, Brazil

Location

CDEC Brasil - Centro de Desenvolvimento em Estudos Clínicos Brasil

São Paulo, São Paulo, CEP 04020-060, Brazil

Location

Instituto do Coração do Hospital das Clínicas da FMUSP

São Paulo, São Paulo, CEP 05403-000, Brazil

Location

Vancouver General Hospital/UBC/VCHA

Vancouver, British Columbia, V5Z 1M9, Canada

Location

St. Boniface General Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

Location

Capital District Health Authority

Halifax, Nova Scotia, B3H 2E2, Canada

Location

McMaster University Medical Centre, Hamilton Health Sciences

Hamilton, Ontario, L8S 2X2, Canada

Location

Kingston General Hospital Sleep Disorders Laboratory/Queen's University

Kingston, Ontario, K7L 2V6, Canada

Location

St. Mary's General Hospital

Kitchener, Ontario, N2M 1B2, Canada

Location

London Health Sciences Centre - Victoria Hospital

London, Ontario, N6C 2R5, Canada

Location

University of Ottawa-Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

University Health Network/TRI/Mount Sinai

Toronto, Ontario, M5G 2C4, Canada

Location

Hôpital Hôtel-Dieu du CHUM

Montreal, Quebec, H2X 0C1, Canada

Location

McGill University Health Centre, Glen Site

Montreal, Quebec, H4A 3J1, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval

Québec, Quebec, G1V 4G5, Canada

Location

Centre Hospitalier de Béziers

Béziers, 34500, France

Location

Pole d'exploration de L' apnée du sommeil, Nouvelle Clinique Bel Air

Bordeaux, 33200, France

Location

Groupe Hospitalier Ambroise Paré, AP-HP

Boulogne-Billancourt, 92100, France

Location

Hôpital Antoine Béclère, AP-HP

Clamart, 92141, France

Location

Laboratoire d'Explorations Fonctionnelles Cardio-Respiratoires, Centre Hospitalier Universitaire de Grenoble

Grenoble, 38043, France

Location

Hôpital Bichat- Claude Bernard, AP-HP

Paris, 75018, France

Location

Groupe Hospitalier Pitié-Salpêtrière Charles Foix, AP-HP

Paris, 75651, France

Location

University of Regensburg

Regensburg, Bavaria, 93053, Germany

Location

Wissenschaftliches Institut Bethanien e.V.

Solingen, 42699, Germany

Location

ASST Franciacorta, Ospedale di Chiari

Chiari, BS, 25032, Italy

Location

Prima Medicina-Spedali Civili

Brescia, 25123, Italy

Location

Istituto Auxologico Italiano - Ospedale San Luca

Milan, 20149, Italy

Location

Istituto Scientifico di Montescano, Istituti Clinici Scientifici Maugeri (ICS Maugeri)

Pavia, 27040, Italy

Location

Istituto Scientifico di Veruno, Istituti Clinici Scientifici Maugeri

Veruno, 28010, Italy

Location

Saiseikai Futsukaichi Hospital

Fukuoka, 818-8516, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Toranomon Hospital

Tokyo, 105-8470, Japan

Location

Juntendo University School of Medicine

Tokyo, 113-8421, Japan

Location

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, 10003, Spain

Location

Hospital Arnau de Vilanova

Lleida, 25198, Spain

Location

Fundación Jiménez Diaz-CAPIO

Madrid, 28040, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Rio Hortega

Valladolid, 47012, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Hospital Universitario Txagorritxu

Vitoria-Gasteiz, Álava, 01009, Spain

Location

The Sleep Disorders Centre -Nuffield House, Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Related Publications (3)

• Horvath CM, Fisser C, Floras JS, Sossalla S, Wang S, Tomlinson G, Rankin F, Yatsu S, Ryan CM, Bradley TD, Arzt M; ADVENT-HF Investigators. Nocturnal Cardiac Arrhythmias in Heart Failure With Obstructive and Central Sleep Apnea. Chest. 2024 Dec;166(6):1546-1556. doi: 10.1016/j.chest.2024.08.003. Epub 2024 Aug 20.

  PMID: 39168180 DERIVED

• Bradley TD, Logan AG, Lorenzi Filho G, Kimoff RJ, Duran Cantolla J, Arzt M, Redolfi S, Parati G, Kasai T, Dunlap ME, Delgado D, Yatsu S, Bertolami A, Pedrosa R, Tomlinson G, Marin Trigo JM, Tantucci C, Floras JS; ADVENT-HF Investigators. Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial. Lancet Respir Med. 2024 Feb;12(2):153-166. doi: 10.1016/S2213-2600(23)00374-0. Epub 2023 Dec 21.

  PMID: 38142697 DERIVED

• 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.

  PMID: 29065956 DERIVED

MeSH Terms

Conditions

Sleep Apnea Syndromes; Heart Failure; Sleep Apnea, Obstructive; Sleep Apnea, Central

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• Douglas Bradley, M.D.

  Toronto Rehabilitation Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Chairman

Study Record Dates

• First Submitted: April 26, 2010
• First Posted: May 24, 2010
• Study Start: May 1, 2010
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: November 22, 2022

Record last verified: 2022-11

Locations

BR (4); CA (13); DE (2); IT (5); ES (9); GB (1); FR (7); JP (5); US (3)