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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Sleep Apnea, Heart Failure

Intervention / Treatment
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* Device: Adaptive Servo Ventilation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard HF therapy<br>Subjects will receive optimal standard therapy for heart failure conforming to national guidelines as determined by the referring cardiologist | |
| Active Comparator: Standard therapy for HF + ASV<br>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<br>* BiPAP autoSV ADVANCED device worn nightly during sleep<br>* Other names: Respironics;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to death from any cause | The study will end once 540 primary endpoints have occurred. | 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 | 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 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 | 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 | 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. | 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 | 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. | Values obtained at study termination will be compared to those obtained at randomization | 
| Changes in apnea/hypopnea index |  | 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. | Assessments made at baseline, 1, 6, 12 and every 6 months thereafter | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obstructive sleep apnea, central sleep apnea, heart failure, congestive heart failure, adaptive servo ventilation, ASV