Effects of Rolofylline, a New Adenosine A1 Receptor Antagonist, on Symptoms, Renal Function, and Outcomes in Patients With Acute Heart Failure - PROTECT Pilot


The goal of this trial was to evaluate treatment with the adenosine A1 receptor antagonist rolofylline compared with placebo in patients with acute heart failure (HF).


Rolofylline will be more effective in improving clinical outcomes and preserving renal function.

Study Design

Patients Enrolled: 301
Mean Follow Up: 60 days
Mean Patient Age: 72 years
Female: 41

Patient Populations:

• Acute HF requiring intravenous diuretic therapy within 24 hours of admission
• History of HF for at least 14 days with diuretic therapy
• Estimated creatinine clearance of 20-80 ml/min
• Systolic blood pressure >95 mm Hg
• Age ≥18 years


• B-type natriuretic peptide (BNP) <250 pg/ml="" or="" nt-probnp=""><1000>
• Severe pulmonary disease
• Significant valve stenosis
• Acute coronary syndrome in the 2 weeks prior to screening
• High risk for seizure (history of seizure, stroke, brain tumor, or brain surgery within 2 years)

Primary Endpoints:

Distribution among 3 categories:
• Treatment success on days 2 and 3 (dyspnea improvement)
• Treatment failure (death or HF readmission through day 7, worsening HF, creatinine increase ≥0.3 mg/dl on day 7 and confirmed on day 14)
• Treatment unchanged (neither treatment success nor failure)

Secondary Endpoints:

• Change in creatinine at 14 days
• Change in mortality at 60 days
• Rehospitalization for HF at 60 days

Drug/Procedures Used:

Patients with acute HF were randomized to rolofylline (30 mg, n = 74; 20 mg, n = 75; 10 mg, n = 74) or placebo (n = 78).

Concomitant Medications:

In the 30 mg rolofylline group, the use of the following medications at baseline was: 73% for angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker, 65% for beta-blocker, and 37% for aldosterone inhibitor.

Principal Findings:

Serum creatinine at enrollment was 1.4, 1.7, and 1.5 mg/dl in the 30, 20, and 10 mg groups, respectively and 1.5 mg/dl for placebo.

Fewer patients in the 30 mg rolofylline group experienced an increase in serum creatinine of more than 0.3 mg/dl compared with placebo (p


Among patients with acute decompensated HF, the use of rolofylline 30 mg resulted in less worsening of renal function. There was also a favorable trend in the reduction in death or HF hospitalization for the 30 mg group. There were no adverse events reported with rolofylline.

This pilot study on the use of an adenosine receptor antagonist in decompensated HF shows promise in preserving renal function and possibly reducing adverse events.


Effects of Rolofylline, a New Adenosine A1 Receptor Antagonist, on Symptoms, Renal Function, and Outcomes in Patients With Acute Heart Failure: Results of the PROTECT Pilot Study. Presented by Dr. Barry Massie at the SCAI-ACC i2 Summit/American College of Cardiology Annual Scientific Session, Chicago, IL, March/April 2008.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Adenosine A1 Receptor Antagonists, Diuretics, Heart Failure, Blood Pressure, Xanthines, Creatinine, Receptor, Adenosine A1

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