Design and rationale of the PROTECT study: a placebo-controlled randomized study of the selective A1 adenosine receptor antagonist rolofylline for patients hospitalized with acute decompensated heart failure and volume overload to assess treatment effect on congestion and renal function.

Journal Article (Journal Article;Multicenter Study)

BACKGROUND: Current treatment for acute decompensated heart failure (ADHF) is associated with incomplete resolution of symptoms and signs, recurrent symptoms of heart failure in-hospital and after discharge and high mortality. Studies have consistently demonstrated an association between worsening renal function in ADHF and adverse outcomes. Adenosine A(1) receptor antagonists, such as rolofylline, appear in preliminary studies to produce potentially beneficial effects on natriuresis, diuresis, renal blood flow, and glomerular filtration rate. In a previous dose-finding study, rolofylline 30 mg intravenously daily for 3 days was associated with symptom improvement, less worsening of renal function, and trends toward lower 60-day rates of death or readmission for cardiovascular or renal causes. METHODS AND RESULTS: This manuscript describes the rationale underlying the design of the phase 3 PROTECT (Placebo-controlled Randomized study of the selective A(1) adenosine receptor antagonist rolofylline for patients hospitalized with acute heart failure and volume Overload to assess Treatment Effect on Congestion and renal funcTion) trial. CONCLUSION: Rolofylline 30 mg or matching placebo was given intravenously as a 4-hour continuous infusion on 3 consecutive days and the hospital course was assessed by measurements dyspnea, clinical status, renal function, and subsequent morbidity and mortality in a large population of patients with ADHF with renal impairment.

Full Text

Duke Authors

Cited Authors

  • Weatherley, BD; Cotter, G; Dittrich, HC; DeLucca, P; Mansoor, GA; Bloomfield, DM; Ponikowski, P; O'Connor, CM; Metra, M; Massie, BM; PROTECT Steering Committee, Investigators, and Coordinators,

Published Date

  • January 2010

Published In

Volume / Issue

  • 16 / 1

Start / End Page

  • 25 - 35

PubMed ID

  • 20123315

Electronic International Standard Serial Number (EISSN)

  • 1532-8414

Digital Object Identifier (DOI)

  • 10.1016/j.cardfail.2009.10.025


  • eng

Conference Location

  • United States