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.
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.


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.


CONCLUSIONS
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.
Weatherley
Beth Davison
BD
Momentum Research, Inc., Durham, NC.
Cotter
Gad
G
Dittrich
Howard C
HC
DeLucca
Paul
P
Mansoor
George A
GA
Bloomfield
Daniel M
DM
Ponikowski
Piotr
P
O'Connor
Christopher M
CM
Metra
Marco
M
Massie
Barry M
BM
D058916:Adenosine A1 Receptor Antagonists; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D007677:Kidney Function Tests / Q000379:methods* / Q000639:trends*; D008297:Male; D010865:Pilot Projects; D043682:Receptor, Adenosine A1 / Q000502:physiology; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome; D014970:Xanthines / Q000494:pharmacology / Q000627:therapeutic use*
D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D014970:Xanthines; C073525:rolofylline