Condition category
Circulatory System
Date applied
29/04/2010
Date assigned
30/04/2010
Last edited
01/04/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Heart failure is caused by the heart not pumping enough blood around the body at the right pressure. People with heart failure often have breathing problems while they sleep (sleep apnea), such as obstructive sleep apnoea, where the walls of the throat narrow and interrupt breathing, and central sleep apnoea, where the brain fails to send signals to the breathing muscles. Adaptive Servo Ventilation (ASV) machines can be used to treat sleep apnoea by providing support to regular breathing during sleep. This study will test whether ASV treatment improves outcomes for heart failure patients with obstructive sleep apnea and/or central sleep apnea.

Who can participate?
Heart failure patients aged 18 or over with obstructive sleep apnea and/or central sleep apnea.

What does the study involve?
Participants are randomly allocated to receive either standard treatment for heart failure or both standard treatment and an ASV machine to use during sleep.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Toronto Rehabilitation Institute (Canada)

When is the study starting and how long is it expected to run for?
May 2010 to September 2017

Who is funding the study?
1. Canadian Institutes of Health Research (CIHR) (Canada)
2. Philips Respironics Inc.

Who is the main contact?
Dr Douglas Bradley

Trial website

Contact information

Type

Scientific

Primary contact

Dr Douglas Bradley

ORCID ID

Contact details

Toronto Rehabilitation Institute
550 University Avenue
12 floor
Toronto
M5G 2A2
Canada

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01128816

Protocol/serial number

IS2-95225

Study information

Scientific title

Multi-centre, randomized study to assess the effects of adaptive servo ventilation on survival and frequency of cardiovascular hospital admissions in patients with heart failure and sleep apnea: the ADVENT-HF trial

Acronym

ADVENT-HF

Study hypothesis

This study will test the hypothesis that in a long-term multi-centre randomized clinical trial (RCT), treatment of Obstructive Sleep Apnea and/or Central Sleep Apnea with Adaptive Servo Ventilation in subjects with Heart Failure will:
1. Reduce the composite primary endpoint of death from all causes, cardiovascular hospitalizations, new onset atrial fibrillation/flutter requiring anticoagulation but not hospitalization, or delivery of an appropriate shock from an ICD, not resulting in hospitalization
2. Cause regression of left ventricular remodelling
3. Reduce plasma levels of N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP)
4. Improve submaximal exercise capacity
5. Improve quality of life

Ethics approval

University Health Network Research Ethics Board, University of Toronto, 11/03/2010, ref: REB # 09-0834-B

Study design

Multicentre randomized parallel-group open label trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please contact Dr. Douglas Bradley [douglas.bradley@utoronto.ca] for more information

Condition

Heart failure; sleep apnea

Intervention

Eligible participants will be randomized to receive either standard optimized treatment for Heart Failure conforming to national guidelines plus Adaptive Servo Ventilation to be worn during sleep or standard optimized treatment for Heart Failure conforming to national guidelines alone.

Intervention type

Device

Phase

Drug names

Primary outcome measures

Time from randomization to death from all causes or to the first hospitalization for a cardiovascular cause or new onset atrial fibrillation/flutter requiring anticoagulation but not hospitalization, or delivery of an appropriate shock from an ICD, not resulting in hospitalization. The trial will end when 540 primary outcomes have been adjudicated.

Secondary outcome measures

1. Time from randomization to death from any cause
2. Time from randomization to CV hospitalizations, new onset atrial fibrillation/flutter requiring anticoagulation but not hospitalization, or delivery of an appropriate shock from an ICD, not resulting in hospitalization
3. Number of days alive not hospitalised
4. Changes in left ventricular function at 6 months post randomization
5. Changes in plasma NT-proBNP levels at 6 months post randomization
6. Occurrence of CRT or AICD implantation
7. Change in 6-minute walk test distance at 6 months post randomization
8. Changes in American Heart Association/American College of Cardiology stages of HF and changes in New York Heart Association class measured at 1 month, 3 months, 6 months and every 6 months thereafter post randomization until study end
8. Changes in apnea-hypopnea index (AHI) measured at 1 month post randomization
9. Changes in quality of life assessed by the Minnesota Living With Heart Failure questionnaire and Epworth Sleepiness Scale measured at 1 month, 3 months, 6 months and every 6 months thereafter post randomization until study completion

Overall trial start date

10/05/2010

Overall trial end date

01/09/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male or female 18 years or older
2. Documented American Heart Association Stages B, C and D HF due to ischemic, idiopathic or hypertensive causes for at least 3 months
3. Left ventricular ejection fraction (LVEF) ≤ 45%, as determined by echocardiography at screening
4. On optimal medical therapy conforming to contemporary national or American Heart Association guidelines, as determined by the patient's primary cardiologist
5. No changes in active cardiac medication during 2 weeks prior to randomization; if patient is on a beta-blocker, beta-blocker therapy must have been started at least 3 months prior to randomization
6. Sleep apnea with an Apnea/Hypopnea Index (AHI) ≥ 15, which will be divided into Obstructive Sleep Apnea (OSA) (greater than or equal to 50% events obstructive), or Central Sleep Apnea (CSA) (> 50% of events central in nature). For patients with OSA, an Epworth Sleepiness Scale (ESS) score of ≤ 10 and no or mild daytime sleepiness (by the International Classification of Sleep Disorders: occasionally falling asleep during passive situations, is considered mild and not pathological). For patients with CSA, no ESS or subjective sleepiness criteria will be used, since there is very little evidence that CSA is associated with hypersomnolence, or that treating CSA reduces sleepiness.
7. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

860 randomized participants

Participant exclusion criteria

1. HF due to primary valvular heart disease
2. Presence of moderate to severe mitral insufficiency due to intrinsic mitral valve disease. If mitral insufficiency is secondary to the cardiomyopathic state, patients can be included
3. Hypertrophic obstructive or restrictive or post partum cardiomyopathy
4. Exercise capacity limited by class IV angina pectoris
5. Acute Myocardial Infarction (MI), cardiac surgery, Percutaneous Coronary Intervention (PCI), Automatic Implantable Cardioverter Defibrillator (AICD)-if implanted for pacing function or secondary prevention , or Cardiac Resynchronization Therapy (CRT) within 3 months of randomization; only a 2-week waiting period before randomization is required if the AICD is implanted for primary prevention
6. Active myocarditis
7. Planned AICD or CRT
8. Presence of a left-ventricular assist device (LVAD)
9. Transplanted heart or expected to receive a transplanted heart within the next 6 months
10. Pregnancy
11. Current use of ASV, BiPAP, CPAP or mandibular advancement device for treatment of sleep apnea or treatment with any investigational therapy during the last 4 weeks (including approved therapies being used in unapproved indications)
12. A clinical history that would interfere with the objectives of this study or that would in the investigator's opinion reduce 5 year life expectancy
13. 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)
14. Any contraindication to ASV therapy as detailed in the device provider manual

Recruitment start date

10/05/2010

Recruitment end date

30/04/2017

Locations

Countries of recruitment

Brazil, Canada, France, Germany, Japan, Spain, United Kingdom, United States of America

Trial participating centre

University Health Network - Toronto Rehabilitation Institute
550 University Avenue
Toronto
M5G 2A2
Canada

Sponsor information

Organisation

University Health Network/Toronto Rehabilitation Institute (Canada)

Sponsor details

c/o Dr Douglas Bradley
550 University Avenue-12 floor]
Toronto
M5G 2A2
Canada

Sponsor type

Research organisation

Website

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (ref: IS2-95225)

Alternative name(s)

Instituts de Recherche en Santé du Canada, CIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Canada

Funder name

Unrestricted gift from Philips Respironics Inc.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

01/04/2016: Plain English summary added. 16/09/2015: Overall trial end date updated from 10/05/2015 to 01/09/2017 Recruitment end date updated from 10/05/2015 to 30/04/2017. Hypothesis point 1 updated from "Reduce the composite primary endpoint of death, heart transplantation, left ventricular assist device implantation and cardiovascular hospitalizations" to "Reduce the composite primary endpoint of death from all causes, cardiovascular hospitalizations, new onset atrial fibrillation/flutter requiring anticoagulation but not hospitalization, or delivery of an appropriate shock from an ICD, not resulting in hospitalization" Outcome measures updated to include "new onset atrial fibrillation/flutter requiring anticoagulation but not hospitalization, or delivery of an appropriate shock from an ICD, not resulting in hospitalization"