Cardiovascular Improvements With MV ASV Therapy in Heart Failure

N/ATerminatedNCT01953874

ResMed126 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Enrollment

126

Conditions

Acute Decompensated Heart Failure Sleep Disordered Breathing

Interventions

MV ASVDEVICE

Minute ventilation-targeted servo-ventilation therapy.

Optimized Medical TreatmentDRUG

Beta Blockers, ACE inhibitor or ARB, loop diuretics and/or spironolactone as appropriate, statin if indicated, aspirin and/or warfarin if indicated

Eligibility

Sex: ALLMin age: 21 Years

Medical Language ↔ Plain English

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

Locations (15)

The Heart Center

Huntsville, Alabama, United States

VA Greater Los Angeles Healthcare System

Los Angeles, California, United States

Outcomes

Primary Outcomes

Global Rank Endpoint

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.

Time frame: Baseline, 6 months

Secondary Outcomes

Six-minute Walk Distance

Change in functional parameters as measured by 6-minute walk test (6MWT)

Time frame: Change from Baseline to 6 months

NT Pro-BNP

Change in neurohumoral activation as measured by N-terminal pro b-type natriuretic peptide.

Time frame: Change from Baseline to 6 months

Kansas City Cardiomyopathy Questionnaire (KCCQ)

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.

Time frame: Change from Baseline to 6 months

Biomarkers - Inflammation

Biomarkers of inflammation reported as troponin I ultra-sensitive

Time frame: Change from Baseline to 6 months

Biomarkers - Cardiovascular

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Denver, Colorado, United States

Mercer University

Macon, Georgia, United States

Northwestern University

Chicago, Illinois, United States

University of Maryland

Baltimore, Maryland, United States

St. Luke's Hospital of Kansas City

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

...and 5 more locations

Biomarkers of cardiovascular function reported as hs-CRP

Time frame: Change from Baseline to 6 months

Biomarkers - Renal Function

Biomarkers of renal function reported as creatinine

Time frame: Change from Baseline to 6 months

ECHO Parameters - LVEF

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).

Time frame: Change from Baseline to 6 months

ECHO Parameters - LVESVI

Time frame: Change from Baseline to 6 months

ECHO Parameters - E/e' Ratio

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).

Time frame: Change from Baseline to 6 months

Win Ratio

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.

Time frame: 6 months

Sleep Parameters

Sleep and sleep disordered breathing parameters (AHI, nocturnal hypoxemia)

Time frame: Change from Baseline to 6 months

Number of Subjects With HF Hospitalization

Rates of hospitalization or urgent clinic visit for worsening of heart failure and for any reason

Time frame: 2 days, 1 week, 1, 2, 3, and 6 months

Death

Rate of Cardiovascular and all-cause death

Time frame: 2 days, 1 week, 1, 2, 3, and 6 months

Time Dead/Hospitalized

Total days dead or hospitalized at study end

Time frame: 6 months

DASI

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.

Time frame: Change from Baseline to 6 months

EQ-5D-5L Index

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.

Time frame: Change from Baseline to 6 months

PHQ-9

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.

Time frame: Change from Baseline to 6 months

PSQI

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.

Time frame: Change from Baseline to 6 months

ESS

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.

Time frame: Change from Baseline to 6 months