Cardiovascular Improvements With MV ASV Therapy in Heart Failure

Not Applicable

Terminated

Conditions: Acute Decompensated Heart Failure
Sleep Disordered Breathing

Interventions: Drug: Optimized Medical Treatment
Device: MV ASV

Registration Number: NCT01953874

Lead Sponsor: ResMed

Brief Summary: The aim of the study is to compare the effects of MV targeted ASV in addition to optimized medical therapy versus optimized medical therapy alone at 6 months in patients with acute decompensated HF. The study will also assess changes in functional parameters, biomarkers, quality of life (QOL), and sleep.

Detailed Description: This study is a randomized, unblinded, multi-center trial with parallel group design, with subjects randomized to either control (optimized medical therapy for chronic heart failure) or active treatment (optimized medical therapy plus use of MV-targeted ASV) in a 1:1 ratio.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 126

Inclusion Criteria

Patients 21 years or older
Patients with prior clinical diagnosis of heart failure (HFrEF or HFpEF), or de novo diagnosis of HFpEF indicated by a local BNP≥300 pg/mL or NT pro-BNP≥1200 pg/mL on admission without systolic blood pressure >180 mmHg or atrial fibrillation, or diagnosis of HFrEF indicated by documented evidence of prescribed beta-blockers and ACE-inhibitors or ARBs for at least 4 weeks prior to admission
Hospital admission for acute decompensated HF as determined by:
- Dyspnea at rest or with minimal exertion
  - AND At least two of the following signs and symptoms:
- Orthopnea
- Pulmonary rales beyond basilar
- Chest congestion on x-ray
- BNP≥300pg/mL or NT pro-BNP≥1200pg/mL
- Pulmonary capillary wedge pressure (PCWP) ≥25mmHg during current hospitalization
Presented to hospital or clinic at least 24 hours prior to consent
Patient stable enough to stop oxygen use for duration of polygraphy test or have access to dual lumen cannula for polygraphy test
Sleep disordered breathing (SDB) documented by polygraphy with an AHI≥15 events/hour
Patient is able to fully understand study information and sign a consent form

Exclusion Criteria

Right-sided heart failure without left-sided heart failure
Sustained systolic blood pressure <80 mmHg at baseline
Acute coronary syndrome within 1 months of randomization
Active myocarditis
Complex congenital heart disease
Constrictive pericarditis
Non-cardiac pulmonary edema
Clinical evidence of digoxin toxicity
Need for mechanical hemodynamic support at time of randomization
Oxygen saturation ≤85% at rest during the day or at start of nocturnal oximetry recording or regular use of oxygen therapy (day or night)
COPD exacerbation as the primary reason for hospital admission
Current use (within 4 weeks of study entry) of any PAP-therapy (eg, fixed, bi-level, or APAP)
Life expectancy < 1 year for diseases unrelated to HF
Transient ischemic attack (TIA) or Stroke within 3 months prior to randomization
CABG procedure within 3 months prior to randomization, or planned to occur during study period
CRT implant within 3 months prior to randomization , or planned to occur during study period
VAD implant planned to occur during study period
Heart transplant list Status 1a or 1b
Status post-transplant or LVAD
Prescribed inotrope therapy anticipated at discharge
Chronic Dialysis
Known amyloidosis, hypertrophic obstructive cardiomyopathy, arteriovenous fistulas
Primary hemodynamically significant uncorrected valvular heart disease (obstructive or regurgitant) with planned intervention within 6 months of randomization
Pregnant, or planning to become pregnant
Cannot tolerate ASV treatment during run-in
Cannot perform 6MWT at baseline
Occupation as a commercial driver or pilot and plan to be performing these activities during the study period
Inability to comply with planned study procedures
Participation in pharmaceutical or treatment-related clinical study within 1 month of study enrollment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OMT only	Optimized Medical Treatment	Optimized Medical Treatment for heart failure in accordance with applicable guidelines (ACCF/AHA Guideline for the Management of Heart Failure and HFSA Heart Failure Guidelines.
MV ASV+OMT	MV ASV	Minute Ventilation-targeted adaptive servo-ventilation therapy plus optimized medical treatment
MV ASV+OMT	Optimized Medical Treatment	Minute Ventilation-targeted adaptive servo-ventilation therapy plus optimized medical treatment

Primary Outcome Measures

Name	Time	Method
Global Rank Endpoint	Baseline, 6 months	A rank order response based on survival free from CV hospitalization and improvement in functional capacity measured by 6MWD. All participants were first ranked by time to death, then ranked by time to CV hospitalization, and then ranked by percentage change in 6MWD. For time to event measures (time to death and time to hospitalization), the shorter the amount of time, the lower the rank assigned to that participant. For percentage changes in 6MWD, the smaller the percentage change, the lower the rank assigned to that participant. Each component was then combined to create a rank value that ranged between 0 and 100. Overall, higher rank values are associated with better outcomes.

Secondary Outcome Measures

Name	Time	Method
Kansas City Cardiomyopathy Questionnaire (KCCQ)	Change from Baseline to 6 months	The KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
Six-minute Walk Distance	Change from Baseline to 6 months	Change in functional parameters as measured by 6-minute walk test (6MWT)
NT Pro-BNP	Change from Baseline to 6 months	Change in neurohumoral activation as measured by N-terminal pro b-type natriuretic peptide.
ECHO Parameters - LVEF	Change from Baseline to 6 months	Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFrEF or HFpEF (heart failure with preserved ejection fraction).
ECHO Parameters - LVESVI	Change from Baseline to 6 months	Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFrEF or HFpEF (heart failure with preserved ejection fraction).
Biomarkers - Inflammation	Change from Baseline to 6 months	Biomarkers of inflammation reported as troponin I ultra-sensitive
Biomarkers - Cardiovascular	Change from Baseline to 6 months	Biomarkers of cardiovascular function reported as hs-CRP
Biomarkers - Renal Function	Change from Baseline to 6 months	Biomarkers of renal function reported as creatinine
ECHO Parameters - E/e' Ratio	Change from Baseline to 6 months	Echocardiographic parameters, including LVEF (left ventricular ejection fraction) and LVESVI (left ventricular end-systolic volume index) for patients with HFrEF (heart failure with reduced ejection fraction), and E/e' (ratio between early mitral inflow velocity and mitral annular early diastolic velocity) for patients with HFpEF (heart failure with preserved ejection fraction).
Win Ratio	6 months	Patients in the new treatment and control groups are formed into matched pairs based on their risk profiles. For each matched pair, the new treatment patient is labeled a 'winner' or a 'loser' depending on who had a CV death first. If that is not known, they are labeled a 'winner' or 'loser' depending on who had a HF hospitalization first. Otherwise they are considered tied. The win ratio is the total number of winners divided by the total numbers of losers.
Sleep Parameters	Change from Baseline to 6 months	Sleep and sleep disordered breathing parameters (AHI, nocturnal hypoxemia)
Number of Subjects With HF Hospitalization	2 days, 1 week, 1, 2, 3, and 6 months	Rates of hospitalization or urgent clinic visit for worsening of heart failure and for any reason
EQ-5D-5L Index	Change from Baseline to 6 months	The EQ-5D-5L is a standardized self-report questionnaire that is used as a measure of health outcome. The EQ-5D-5L questionnaire is comprised of the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses were indexed using the EQ-5D-5L US value set to scale the 5 dimensions. A score of -0.109 indicates extreme problems for all dimensions and a score of 1.000 indicates no problems for all dimensions. Therefore, a higher score indicates better general health.
PSQI	Change from Baseline to 6 months	The Pittsburgh Sleep Quality Index is a 19-item subjective measurement of sleep. It is an effective instrument used to measure the quality and patterns of sleep in the older adult. It differentiates "poor" from "good" sleep by measuring seven areas: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction over the last month. The subject self-rates each of these seven areas of sleep. The seven component scores are then added to yield a total score with a range of 0-21 points, "0" indicating no difficulty and "21" indicating severe difficulties in all areas.
ESS	Change from Baseline to 6 months	The Epworth Sleepiness Scale is a simple, 8-item self-administered questionnaire which provides a measurement of the subject's general level of daytime sleepiness. The individual is asked on a scale of 0-3 to score the likelihood of falling asleep in eight various situations. With a total range of 0 to 24, a higher score indicates increased severity.
Death	2 days, 1 week, 1, 2, 3, and 6 months	Rate of Cardiovascular and all-cause death
Time Dead/Hospitalized	6 months	Total days dead or hospitalized at study end
DASI	Change from Baseline to 6 months	The Duke Activity Status Index is a 12-item patient-reported outcome validated for the assessment of functional capacity based on the ability to perform everyday activities. With a total range of 0 to 58.20, a higher score indicates better quality of life.
PHQ-9	Change from Baseline to 6 months	The PHQ-9 is the nine item depression scale of the Patient Health Questionnaire. The PHQ-9 is a self-administered instrument for screening, diagnosing, monitoring and measuring the severity of depression. The PHQ-9 incorporates DSM-IV depression diagnostic criteria with other leading major depressive symptoms into a brief self-report tool. The tool rates the frequency of the symptoms which factors into the following scoring severity index: 0 - Not at all, 1 - Several Days, 2 - More than Half the Days, 3 - Nearly Every Day. Total score can range from 0 to 27. A higher score indicates increased severity.

Trial Locations

Locations (15): The Heart Center
🇺🇸
Huntsville, Alabama, United States
Mercer University
🇺🇸
Macon, Georgia, United States
VA Greater Los Angeles Healthcare System
🇺🇸
Los Angeles, California, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
University of Maryland
🇺🇸
Baltimore, Maryland, United States
St. Luke's Hospital of Kansas City
🇺🇸
Kansas City, Missouri, United States
Penn State Hershey
🇺🇸
Hershey, Pennsylvania, United States
Jefferson Heart Institute
🇺🇸
Philadelphia, Pennsylvania, United States
Heart and Diabetes Center - North Rhine-Westphalia (HDZ-NRW)
🇩🇪
Bad Oeynhausen, Germany
Sentara Cardiovascular Research Institute
🇺🇸
Norfolk, Virginia, United States
VA Medical Center
🇺🇸
Denver, Colorado, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
University of Washington
🇺🇸
Seattle, Washington, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States