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

Toronto Rehabilitation Institute732 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

732

Conditions

Sleep Apnea Heart Failure

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (49)

University of Arizona/Southern Arizona VA Health Care System

Tucson, Arizona, United States

Glacier View Research Institute, Kalispell Regional Medical Center

Kalispell, Montana, United States

MetroHealth Medical Centre

Cleveland, Ohio, United States

Pronto Socorro Cardiologico de Pernambuco

Recife, Pernambuco, Brazil

Instituto Dante Pazzanese de Cardiologia

São Paulo, São Paulo, Brazil

Outcomes

Primary Outcomes

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.

Time frame: The expected study follow-up period is five years

Secondary Outcomes

Time to death from any cause

The study will end once 540 primary endpoints have occurred.

Time frame: The expected study follow-up period is 5 years

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

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.

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

Changes in left ventricular function

Changes in LV function will be assessed by echocardiography at baseline and at 6 months post randomization

Time frame: 6 months from randomization

Changes in plasma BNP levels

Changes in plasma NT-proBNP levels will be assessed at baseline and at 6 months post randomization

Time frame: 6 months from 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.

Time frame: Average number of days until first cardiac resynchronization or first defibrillator implantation

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

Time frame: 6 months from randomization

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.

Time frame: Values obtained at study termination will be compared to those obtained at randomization

Changes in apnea/hypopnea index

Time frame: 1 month from randomization

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.

Time frame: Assessments made at baseline, 1, 6, 12 and every 6 months thereafter