To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Rolofylline Reduces Congestion and Improves Renal Function for Patients Hospitalised With Acute Heart Failure and Volume Overload: Presented at HF2008 URL: http://www.pslgroup.com/dg/223EFA.htm Doctor's Guide June 20, 2008
By Chris Berrie MILAN, Italy -- June 20, 2008 -- Infusions of the adenosine A1 receptor antagonist rolofylline are safe and can provide significantly improved renal function and reduced death and rehospitalisation of patients hospitalised for acute heart failure (AHF) who require diuretics, researchers reported here at the Heart Failure 2008 Congress (HF2008). The results of the placebo-controlled, randomised study were presented on June 15 by Gad Cotter, MD, Momentum Research Inc., Durham, North Carolina. "Heart failure is the leading cause of hospitalisation in patients over 65 years of age, and the current practice guidelines include treatment with diuretics," Dr. Cotter said. However, there are suggestions that diuretics can be associated with worsening renal function, which is itself associated with poor prognosis. Early clinical studies showed that rolofylline increases the glomerular filtration rate and renal plasma flow. To determine the preferred dosage regimen of rolofylline, the appropriateness of the primary endpoint, and the safety of rolofylline treatment, Dr. Cotter and colleagues conducted a pilot phase of the ongoing study, Placebo-Controlled, Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT). The study enrolled patients who were 18 years or older, had at least a 14-day history of AHF, and continued to require IV diuretics. Patients had impaired renal function (creatinine clearance 20-80 mL/min) and systolic blood pressure >95 mm Hg. Among 301 patients with AHF with renal impairment and volume overload, 78 patients were randomised to receive placebo (mean age, 70 years; male, 72%), 74 patients to rolofylline 10 mg (mean age, 69 years; male, 58%), 75 patients to rolofylline 20 mg (mean age, 72 years; male, 53%), and 74 patients to receive rolofylline 30 mg (mean age, 72 years; male, 54%). Treatment was infused daily over 4 hours for 3 days. An IV loop diuretic was recommended during active treatment, and lorazepam 1 mg PO daily with active treatment was used prophylactically for patients with intermediate risk of seizures. Effects of treatment were evaluated by patient reports of dyspnoea changes (Likert scale) and central laboratory assessments. The efficacy assessment of rolofylline was decided through a post hoc analysis based on the endpoints for the subsequent phase 3 studies, with results expressed as success, unchanged, and failure, as the primary endpoint. Of note, failure related specifically to death or rehospitalisation for worsening heart failure or renal function through day 7. Patients' clinical and medication baselines were similar across the 4 treatment groups. For the primary endpoint, increasing success was associated with increasing rolofylline dose (nominal P < .05 for dose-related trend at day 14). At 24 hours, dyspnoea improved by 51% in the placebo group and in the rolofylline groups by 62% (10 mg), 63% (20 mg), and 66% (30 mg). Serum creatinine changes to day 14 also reached significant benefit: +0.21, +0.13, +0.03, and -0.04 mg, respectively (placebo vs rolofylline 30 mg, P < .05). Failure rates were 33%, 32%, 24%, and 19%, respectively, providing a trend in the placebo versus rolofylline 30 mg hazard ratio of 0.55 (95% confidence interval, 0.28-1.04). For safety, the rates of adverse events were similar across the treatment groups, and no seizures occurred. Therefore, while data from the ongoing phase 3 trial are awaited, Dr. Cotter noted, "The preservation of renal function associated with rolofylline is the first evidence that an intervention to prevent renal impairment may positively affect acute symptoms and 60-day outcome in patients with acute heart failure." Funding for the PROTECT study was provided by NovaCardia Inc., which is owned by Merck & Co. [Presentation title: A Placebo-Controlled, Randomised Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalised With Acute Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function. Abstract O229] --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. P\S\L shall not be liable for any errors, omissions or delays in this content or any other content on its sites, newsletters or other publications, nor for any decisions or actions taken in reliance on such content. --------------------------------------------------------------------------------------------- This news story was printed from *Doctor's Guide to the Internet* located at http://www.docguide.com --------------------------------------------------------------------------------------- Return to News Story Page This site is maintained by webmaster@pslgroup.com Please contact us with any comments, problems or bugs. All contents Copyright (c) 1998 P\S\L Consulting Group Inc. All rights reserved.