title: 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.
abstract: OBJECTIVE
  The CAT-HF Study was designed to evaluate the safety and efficacy of minute ventilation-targeted adaptive servo-ventilation (MV-ASV) during sleep in addition to optimized medical therapy (active therapy) versus optimized medical therapy alone (usual care) at 6 months, initiated in patients after hospitalization for acute decompensated heart failure (ADHF). This paper outlines the rationale, design and information learned at the time of study discontinuation.
  
  
  BACKGROUND
  Sleep disordered breathing (SDB) is common in heart failure patients and is associated with worse outcomes in this patient population. Based on a belief that MV-ASV was safe in stable HF patients, CAT-HF was designed to examine whether MV-ASV improved outcomes in hospitalized HF patients During the course of CAT-HF, new results from SERVE-HF indicated that ASV therapy may be harmful in patients with left ventricular ejection fractions (LVEF)≤45% and central sleep apnea, a subgroup of patients enrolled in CAT-HF.
  
  
  METHODS
  CAT-HF was a prospective, randomized, controlled, multicenter clinical trial (NCT: 01953874) in HF patients with either reduced or preserved ejection fraction and an Apnea-Hypopnea Index ≥15 events per hour randomized to usual care or active treatment in a 1:1 ratio. 215 patients were intended to be randomized following a hospitalization for ADHF. At the time of discontinuation, 126 patients were randomized. The primary endpoint is a global rank composite endpoint of death, CV hospitalizations, and Six minute walk distance (6MWD). Secondary endpoints will include changes in functional parameters, biomarkers, quality of life (QOL), sleep, and breathing.
  
  
  CONCLUSIONS
  The CAT-HF study was designed to assess the efficacy and safety of MV ASV treatment in patients after hospitalization for ADHF, but was stopped early due to safety concerns in HF patients with (LVEF)≤45% and predominant central sleep apnea.
authors.affiliation: Duke University, Duke Clinical Research Institute, Durham, NC, United States. Electronic address: mona.fiuzat@duke.edu.
authors.forename: Mona
authors.initials: M
authors.lastname: Fiuzat
authors.affiliation: Ruhr University Bochum, Bad Oeynhausen, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Oldenberg
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Whellan
authors.affiliation: ResMed Science Center, ResMed Corp., San Diego, CA, United States.
authors.forename: Holger
authors.initials: H
authors.lastname: Woehrle
authors.affiliation: Johns Hopkins University, Baltimore, MD, United States.
authors.forename: Naresh M
authors.initials: NM
authors.lastname: Punjabi
authors.affiliation: Duke University, Duke Clinical Research Institute, Durham, NC, United States.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: ResMed Science Center, ResMed Corp., San Diego, CA, United States.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Blase
authors.affiliation: ResMed Science Center, ResMed Corp., San Diego, CA, United States.
authors.forename: Adam V
authors.initials: AV
authors.lastname: Benjafield
authors.affiliation: Vanderbilt University, Nashville, TN, United States.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Lindenfeld
authors.affiliation: Duke University, Duke Clinical Research Institute, Durham, NC, United States; Inova Heart and Vascular Institute, Falls Church, VA, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: O'Connor
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057239:Early Termination of Clinical Trials; D005260:Female; D006333:Heart Failure / Q000150:complications*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D012107:Research Design; D012121:Respiration, Artificial / Q000009:adverse effects / Q000379:methods*; D012891:Sleep Apnea Syndromes / Q000209:etiology / Q000628:therapy*; D016896:Treatment Outcome
keywords: ASV; Heart failure; Hospitalization; Sleep apnea