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

Primary Purpose

Sleep Apnea, Heart Failure

Status
Terminated
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Adaptive Servo Ventilation
Sponsored by
Toronto Rehabilitation Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Apnea focused on measuring obstructive sleep apnea, central sleep apnea, heart failure, congestive heart failure, adaptive servo ventilation, ASV

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arizona/Southern Arizona VA Health Care System
  • Glacier View Research Institute, Kalispell Regional Medical Center
  • MetroHealth Medical Centre
  • Pronto Socorro Cardiologico de Pernambuco
  • Instituto Dante Pazzanese de Cardiologia
  • CDEC Brasil - Centro de Desenvolvimento em Estudos Clínicos Brasil
  • Instituto do Coração do Hospital das Clínicas da FMUSP
  • Vancouver General Hospital/UBC/VCHA
  • St. Boniface General Hospital
  • Capital District Health Authority
  • McMaster University Medical Centre, Hamilton Health Sciences
  • Kingston General Hospital Sleep Disorders Laboratory/Queen's University
  • St. Mary's General Hospital
  • London Health Sciences Centre - Victoria Hospital
  • University of Ottawa-Ottawa Heart Institute
  • St. Michael's Hospital
  • University Health Network/TRI/Mount Sinai
  • Hôpital Hôtel-Dieu du CHUM
  • McGill University Health Centre, Glen Site
  • Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval
  • Pole d'exploration de L' apnée du sommeil, Nouvelle Clinique Bel Air
  • Groupe Hospitalier Ambroise Paré, AP-HP
  • Centre Hospitalier de Béziers
  • Hôpital Antoine Béclère, AP-HP
  • Laboratoire d'Explorations Fonctionnelles Cardio-Respiratoires, Centre Hospitalier Universitaire de Grenoble
  • Hôpital Bichat- Claude Bernard, AP-HP
  • Groupe Hospitalier Pitié-Salpêtrière Charles Foix, AP-HP
  • University of Regensburg
  • Wissenschaftliches Institut Bethanien e.V.
  • ASST Franciacorta, Ospedale di Chiari
  • Prima Medicina-Spedali Civili
  • Istituto Auxologico Italiano - Ospedale San Luca
  • Istituto Scientifico di Montescano, Istituti Clinici Scientifici Maugeri (ICS Maugeri)
  • Istituto Scientifico di Veruno, Istituti Clinici Scientifici Maugeri
  • Saiseikai Futsukaichi Hospital
  • Kyoto University Hospital
  • Toranomon Hospital
  • Juntendo University School of Medicine
  • Tokyo Medical University Hospital
  • Hospital de la Santa Creu i Sant Pau
  • Hospital Universitari Vall d'Hebron
  • Hospital San Pedro de Alcántara
  • Hospital Arnau de Vilanova
  • Fundación Jiménez Diaz-CAPIO
  • Hospital Universitario Marques de Valdecilla
  • Hospital Universitario Rio Hortega
  • Hospital Universitario Miguel Servet
  • Hospital Universitario Txagorritxu
  • The Sleep Disorders Centre -Nuffield House, Guy's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Active Comparator

Arm Label

Standard HF therapy

Standard therapy for HF + ASV

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Time to death from any cause
The study will end once 540 primary endpoints have occurred.
Number of cardiovascular hospitalizations per year of follow-up
Number of days alive not hospitalized
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 left ventricular function
Changes in LV function will be assessed by echocardiography at baseline and at 6 months post randomization
Changes in plasma BNP levels
Changes in plasma NT-proBNP levels will be assessed at baseline and at 6 months post randomization
Cardiac resynchronization therapy or defibrillator implantations
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.
Changes in 6 minute walk test distance
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
New York Heart Association classification and AHA/ACC Stages of Heart Failure will be assessed at each visit.
Changes in apnea/hypopnea index
Changes in Quality of life assessments
Minnesota living with Heart Failure Questionnaire and Epworth Sleepiness Scale will be used. Scores will be compared between the 2 groups.

Full Information

First Posted
April 26, 2010
Last Updated
November 17, 2022
Sponsor
Toronto Rehabilitation Institute
Collaborators
Canadian Institutes of Health Research (CIHR), Philips Respironics
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1. Study Identification

Unique Protocol Identification Number
NCT01128816
Brief Title
Effect of Adaptive Servo Ventilation (ASV) on Survival and Hospital Admissions in Heart Failure
Acronym
ADVENT-HF
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
Philips Global Field Safety Notice for PAP Devices & Ventilators, June 14, 2021 (June 15, 2021 censor date for trial). Patient final visits and collection of endpoints prior to censor date continued to March 31, 2022.
Study Start Date
May 2010 (undefined)
Primary Completion Date
March 31, 2022 (Actual)
Study Completion Date
March 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Toronto Rehabilitation Institute
Collaborators
Canadian Institutes of Health Research (CIHR), Philips Respironics

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Apnea, Heart Failure
Keywords
obstructive sleep apnea, central sleep apnea, heart failure, congestive heart failure, adaptive servo ventilation, ASV

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
732 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard HF therapy
Arm Type
No Intervention
Arm Description
Subjects will receive optimal standard therapy for heart failure conforming to national guidelines as determined by the referring cardiologist
Arm Title
Standard therapy for HF + ASV
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Device
Intervention Name(s)
Adaptive Servo Ventilation
Other Intervention Name(s)
BiPAP autoSV ADVANCED, ASV, Respironics
Intervention Description
BiPAP autoSV ADVANCED device worn nightly during sleep
Primary Outcome Measure Information:
Title
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.
Description
The study will end once 540 primary endpoints have occurred. The maximum follow-up period for all randomized subjects is 5 years.
Time Frame
The expected study follow-up period is five years
Secondary Outcome Measure Information:
Title
Time to death from any cause
Description
The study will end once 540 primary endpoints have occurred.
Time Frame
The expected study follow-up period is 5 years
Title
Number of cardiovascular hospitalizations per year of follow-up
Time Frame
The minimum time of follow-up is expected to be 2 years. The maximum time of follow-up is expected to be 5 years
Title
Number of days alive not hospitalized
Description
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.
Time Frame
Time from randomization to censoring (death, primary event or end of study)
Title
Changes in left ventricular function
Description
Changes in LV function will be assessed by echocardiography at baseline and at 6 months post randomization
Time Frame
6 months from randomization
Title
Changes in plasma BNP levels
Description
Changes in plasma NT-proBNP levels will be assessed at baseline and at 6 months post randomization
Time Frame
6 months from randomization
Title
Cardiac resynchronization therapy or defibrillator implantations
Description
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.
Time Frame
Average number of days until first cardiac resynchronization or first defibrillator implantation
Title
Changes in 6 minute walk test distance
Description
Changes in the 6-minute walk distance between baseline and 6 months will be compared between the 2 groups
Time Frame
6 months from randomization
Title
Percentage of patients with changes in stages of heart failure and functional class
Description
New York Heart Association classification and AHA/ACC Stages of Heart Failure will be assessed at each visit.
Time Frame
Values obtained at study termination will be compared to those obtained at randomization
Title
Changes in apnea/hypopnea index
Time Frame
1 month from randomization
Title
Changes in Quality of life assessments
Description
Minnesota living with Heart Failure Questionnaire and Epworth Sleepiness Scale will be used. Scores will be compared between the 2 groups.
Time Frame
Assessments made at baseline, 1, 6, 12 and every 6 months thereafter

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas Bradley, M.D.
Organizational Affiliation
Toronto Rehabilitation Institute
Official's Role
Study Chair
Facility Information:
Facility Name
University of Arizona/Southern Arizona VA Health Care System
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85723
Country
United States
Facility Name
Glacier View Research Institute, Kalispell Regional Medical Center
City
Kalispell
State/Province
Montana
ZIP/Postal Code
59901
Country
United States
Facility Name
MetroHealth Medical Centre
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109-1998
Country
United States
Facility Name
Pronto Socorro Cardiologico de Pernambuco
City
Recife
State/Province
Pernambuco
ZIP/Postal Code
CEP 50100-060
Country
Brazil
Facility Name
Instituto Dante Pazzanese de Cardiologia
City
São Paulo
State/Province
SP
ZIP/Postal Code
CEP 04012-909
Country
Brazil
Facility Name
CDEC Brasil - Centro de Desenvolvimento em Estudos Clínicos Brasil
City
São Paulo
State/Province
SP
ZIP/Postal Code
CEP 04020-060
Country
Brazil
Facility Name
Instituto do Coração do Hospital das Clínicas da FMUSP
City
São Paulo
State/Province
SP
ZIP/Postal Code
CEP 05403-000
Country
Brazil
Facility Name
Vancouver General Hospital/UBC/VCHA
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
St. Boniface General Hospital
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2A6
Country
Canada
Facility Name
Capital District Health Authority
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2E2
Country
Canada
Facility Name
McMaster University Medical Centre, Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 2X2
Country
Canada
Facility Name
Kingston General Hospital Sleep Disorders Laboratory/Queen's University
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V6
Country
Canada
Facility Name
St. Mary's General Hospital
City
Kitchener
State/Province
Ontario
ZIP/Postal Code
N2M 1B2
Country
Canada
Facility Name
London Health Sciences Centre - Victoria Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6C 2R5
Country
Canada
Facility Name
University of Ottawa-Ottawa Heart Institute
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4W7
Country
Canada
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
University Health Network/TRI/Mount Sinai
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Hôpital Hôtel-Dieu du CHUM
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 0C1
Country
Canada
Facility Name
McGill University Health Centre, Glen Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada
Facility Name
Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
Pole d'exploration de L' apnée du sommeil, Nouvelle Clinique Bel Air
City
Bordeaux
ZIP/Postal Code
33200
Country
France
Facility Name
Groupe Hospitalier Ambroise Paré, AP-HP
City
Boulogne-Billancourt
ZIP/Postal Code
92100
Country
France
Facility Name
Centre Hospitalier de Béziers
City
Béziers
ZIP/Postal Code
34500
Country
France
Facility Name
Hôpital Antoine Béclère, AP-HP
City
Clamart
ZIP/Postal Code
92141
Country
France
Facility Name
Laboratoire d'Explorations Fonctionnelles Cardio-Respiratoires, Centre Hospitalier Universitaire de Grenoble
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Hôpital Bichat- Claude Bernard, AP-HP
City
Paris
ZIP/Postal Code
75018
Country
France
Facility Name
Groupe Hospitalier Pitié-Salpêtrière Charles Foix, AP-HP
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
University of Regensburg
City
Regensburg
State/Province
Bavaria
ZIP/Postal Code
93053
Country
Germany
Facility Name
Wissenschaftliches Institut Bethanien e.V.
City
Solingen
ZIP/Postal Code
42699
Country
Germany
Facility Name
ASST Franciacorta, Ospedale di Chiari
City
Chiari
State/Province
BS
ZIP/Postal Code
25032
Country
Italy
Facility Name
Prima Medicina-Spedali Civili
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Istituto Auxologico Italiano - Ospedale San Luca
City
Milano
ZIP/Postal Code
20149
Country
Italy
Facility Name
Istituto Scientifico di Montescano, Istituti Clinici Scientifici Maugeri (ICS Maugeri)
City
Pavia
ZIP/Postal Code
27040
Country
Italy
Facility Name
Istituto Scientifico di Veruno, Istituti Clinici Scientifici Maugeri
City
Veruno
ZIP/Postal Code
28010
Country
Italy
Facility Name
Saiseikai Futsukaichi Hospital
City
Fukuoka
ZIP/Postal Code
818-8516
Country
Japan
Facility Name
Kyoto University Hospital
City
Kyoto
ZIP/Postal Code
606-8507
Country
Japan
Facility Name
Toranomon Hospital
City
Tokyo
ZIP/Postal Code
105-8470
Country
Japan
Facility Name
Juntendo University School of Medicine
City
Tokyo
ZIP/Postal Code
113-8421
Country
Japan
Facility Name
Tokyo Medical University Hospital
City
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital San Pedro de Alcántara
City
Cáceres
ZIP/Postal Code
10003
Country
Spain
Facility Name
Hospital Arnau de Vilanova
City
Lleida
ZIP/Postal Code
25198
Country
Spain
Facility Name
Fundación Jiménez Diaz-CAPIO
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
Hospital Universitario Rio Hortega
City
Valladolid
ZIP/Postal Code
47012
Country
Spain
Facility Name
Hospital Universitario Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
Hospital Universitario Txagorritxu
City
Vitoria
State/Province
Álava
ZIP/Postal Code
01009
Country
Spain
Facility Name
The Sleep Disorders Centre -Nuffield House, Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
29065956
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. Erratum In: J Clin Sleep Med. 2018 Apr 15;14(4):703.
Results Reference
derived

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

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