Clinical trial NCT01953874: Cardiovascular Improvements With MV ASV Therapy in Heart Failure
Official title: Cardiovascular Improvements With Minute Ventilation-targeted ASV Therapy in Heart Failure (CAT-HF)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Decompensated Heart Failure
Sleep Disordered Breathing
Keywords: heart failure
congestive heart failure
acute decompensated heart failure
chronic heart failure
left-sided heart failure
heart failure decompensation
sleep apnea
sleep disordered breathing
central sleep apnea
obstructive sleep apnea
cheyne-stokes respiration
Lead sponsor: ResMed
Sponsor class: INDUSTRY
Collaborators: name: ResMed Foundation
First posted: 2013-10-01
Enrollment: 126
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Global Rank Endpoint
timeFrame: Baseline, 6 months
Secondary outcomes:
measure: Six-minute Walk Distance
timeFrame: Change from Baseline to 6 months
measure: NT Pro-BNP
timeFrame: Change from Baseline to 6 months
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ)
timeFrame: Change from Baseline to 6 months
measure: Biomarkers - Inflammation
timeFrame: Change from Baseline to 6 months
measure: Biomarkers - Cardiovascular
timeFrame: Change from Baseline to 6 months
measure: Biomarkers - Renal Function
timeFrame: Change from Baseline to 6 months
measure: ECHO Parameters - LVEF
timeFrame: Change from Baseline to 6 months
measure: ECHO Parameters - LVESVI
timeFrame: Change from Baseline to 6 months
measure: ECHO Parameters - E/e' Ratio
timeFrame: Change from Baseline to 6 months
measure: Win Ratio
timeFrame: 6 months
measure: Sleep Parameters
timeFrame: Change from Baseline to 6 months
measure: Number of Subjects With HF Hospitalization
timeFrame: 2 days, 1 week, 1, 2, 3, and 6 months
measure: Death
timeFrame: 2 days, 1 week, 1, 2, 3, and 6 months
measure: Time Dead/Hospitalized
timeFrame: 6 months
measure: DASI
timeFrame: Change from Baseline to 6 months
measure: EQ-5D-5L Index
timeFrame: Change from Baseline to 6 months
measure: PHQ-9
timeFrame: Change from Baseline to 6 months
measure: PSQI
timeFrame: Change from Baseline to 6 months
measure: ESS
timeFrame: Change from Baseline to 6 months
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: The Heart Center
state: Alabama
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Denver
country: United States
facility: VA Medical Center
state: Colorado
city: Macon
country: United States
facility: Mercer University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Kansas City
country: United States
facility: St. Luke's Hospital of Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson Heart Institute
state: Pennsylvania
city: Norfolk
country: United States
facility: Sentara Cardiovascular Research Institute
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Bad Oeynhausen
country: Germany
facility: Heart and Diabetes Center - North Rhine-Westphalia (HDZ-NRW)
Study officials:
affiliation: Duke University
name: Christopher O'Connor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Piccini JP, Pokorney SD, Anstrom KJ, Oldenburg O, Punjabi NM, Fiuzat M, Tasissa G, Whellan DJ, Lindenfeld J, Benjafield A, Woehrle H, Blase A, O'Connor CM. Adaptive servo-ventilation reduces atrial fibrillation burden in patients with heart failure and sleep apnea. Heart Rhythm. 2019 Jan;16(1):91-97. doi: 10.1016/j.hrthm.2018.07.027. Epub 2018 Jul 27.
citation: O'Connor CM, Whellan DJ, Fiuzat M, Punjabi NM, Tasissa G, Anstrom KJ, Benjafield AV, Woehrle H, Blase AB, Lindenfeld J, Oldenburg O. Cardiovascular Outcomes With Minute Ventilation-Targeted Adaptive Servo-Ventilation Therapy in Heart Failure: The CAT-HF Trial. J Am Coll Cardiol. 2017 Mar 28;69(12):1577-1587. doi: 10.1016/j.jacc.2017.01.041.
citation: Fiuzat M, Oldenberg O, Whellan DJ, Woehrle H, Punjabi NM, Anstrom KJ, Blase AB, Benjafield AV, Lindenfeld J, O'Connor CM. Lessons learned from a clinical trial: Design, rationale, and insights from The Cardiovascular Improvements with Minute Ventilation-targeted Adaptive Sero-Ventilation (ASV) Therapy in Heart Failure (CAT-HF) Study. Contemp Clin Trials. 2016 Mar;47:158-64. doi: 10.1016/j.cct.2016.01.001. Epub 2016 Jan 19.