title: Rationale for and design of the TRUE-AHF trial: the effects of ularitide on the short-term clinical course and long-term mortality of patients with acute heart failure.
abstract: The TRUE-AHF is a randomized, double-blind, parallel-group, placebo-controlled trial which is evaluating the effects of a 48-h infusion of ularitide (15 ng/kg/min) on the short- and long-term clinical course of patients with acute heart failure. Noteworthy features of the study include the early enrolment of patients following their initial clinical presentation (within 12 h), and entry blood pressure criteria and thresholds for the adjustment of drug infusion rates, which aim to minimize the risk of hypotension. The trial has two primary endpoints: (i) cardiovascular mortality during long-term follow-up; and (ii) the clinical course of patients during their index hospitalization. Cardiovascular mortality is evaluated in this event-driven trial by following all randomized patients for the occurrence of death until the end of the entire study without truncation at an arbitrarily determined early time point. The clinical course during the index hospitalization is evaluated using the hierarchical clinical composite endpoint, which combines information regarding changes in symptoms and the occurrence of in-hospital worsening heart failure events and death into a single ranked metric that captures interval clinical events and minimizes the likelihood of missing data and confounding due to intensification of background therapy. The design of the TRUE-AHF trial capitalizes on lessons learned from earlier trials and aims to evaluate definitively the potential benefit of ularitide in patients with acute heart failure.
  
  
  
  NCT01661634.
authors.affiliation: Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: Study Biostatistician Wayzata, MN, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Holcomb
authors.affiliation: Ohio State University Heart and Vascular Center, Columbus, OH, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Abraham
authors.affiliation: Innovative Clinical Trials, Department of Cardiology & Pneumology, University Medical Center Göttingen (UMG), Göttingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Anker
authors.affiliation: Division of Cardiology, University of Bergen, Stavanger, Norway.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Dickstein
authors.affiliation: National and Kapodistrian University of Athens, School of Medicine, Attikon Athens University Hospital, Department of Cardiology, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Monash University, Centre of Cardiovascular Research & Education in Therapeutics, Melbourne, Australia.
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.affiliation: Centro Studi ANMCO, Fondazione 'per il Tuo cuore' HCF ONLUS, Firenze, Italy.
authors.forename: Aldo P
authors.initials: AP
authors.lastname: Maggioni
authors.affiliation: Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: John J V
authors.initials: JJV
authors.lastname: McMurray
authors.affiliation: University of Paris, Department of Anesthesia and Critical Care, Hôpitaux Universitaire Saint Louis Lariboisière, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Mebazaa
authors.affiliation: Inova Heart and Vascular Institute, Falls Church, VA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: O'Connor
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Peacock
authors.affiliation: Poland Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Cardiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
authors.affiliation: University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Cardiology, University Hospital Zurich, Zurich, Switzerland.|Cardiorentis AG, Zug, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Holzmeister
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage*; D004232:Diuretics / Q000008:administration & dosage; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D014943:Global Health; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004232:Diuretics; D010446:Peptide Fragments; C056452:Ularitide; D009320:Atrial Natriuretic Factor
keywords: Acute heart failure; Clinical composite endpoint; Randomized clinical trials; Ularitide