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| |  Study Fails to Demonstrate Efficacy, Safety of Tonapofylline for Decompensated Heart Failure: Presented at Heart Failure 2010 By Betty S. Riggs BERLIN -- June 2, 2010 -- Treatment of patients with acute decompensated heart failure (ADHF) with tonapofylline produced no significant reduction of body weight or decrease in length of hospital stay and increased risk of neurological adverse events, researchers said here at the European Society of Cardiology's Heart Failure Congress 2010. Markku S. Nieminen, MD, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland, reported findings from the Study to Assess the Safety and Tolerability of IV Tonapofylline in Subjects With Acute Decompensated Heart Failure and Renal Insufficiency (TRIDENT-1) trial here on May 30 during a Late-Breaking Trials Session. TRIDENT-1 was conducted to explore the safety, tolerability, and clinical effects of intravenous (IV) tonapofylline, a potent adenosine A1-receptor antagonist, in patients with ADHF and renal dysfunction. In the study, adult patients with chronic heart failure with volume overload and renal insufficiency who required hospitalisation and who received at least 40 mg of intravenous furosemide were randomised to tonapofylline 0.03, 0.15, or 0.30 mg/kg every 12 hours for 2 to 5 days or placebo. The primary efficacy endpoints were change in body weight at 24 hours, improvements in Dyspnea Symptom Score, percentage of patients with worsening renal function, length of hospitalisation, days of hospital-free survival, and all-cause mortality or cardiovascular re-hospitalisation. The trial was terminated early (August 2009), following review of interim efficacy (renal function) data by the Independent Data Monitoring Committee. There were no statistically significant differences between placebo and active treatment with regard to body weight change. There were also no significant between-group differences in the percent of subjects with improved dyspnoea or subjects with worsened renal function. The length of hospital stay and days of hospital-free survival were not improved with active therapy. The number of patients with any adverse event was 61, 63, 62, and 62 for placebo and the 3 tonapofylline groups, respectively. However, none of the placebo patients experienced a neurological serious adverse event compared with 4 patients receiving tonapofylline. One convulsion occurred in the middle-dose group of tonapofylline and 1 simple partial seizure occurred in the high-dose group. The absence of a clear efficacy signal with an approximate 1% risk of seizure led to early trial termination, and these results do not support the further development of this drug. Funding for this study was provided by Biogen Idec. [Presentation title: Results of the TRIDENT-1 Trial: A Phase 2b Study to Assess the Safety and Tolerability of IV Tonapofylline in Subjects With Acute Decompensated Heart Failure and Renal Insufficiency]
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