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| |  Primary Endpoints Not Met in Rolofylline for Heart Failure Study: Presented at ESC By Walter Alexander BARCELONA, Spain -- September 4, 2009 -- In contrast to the promising results demonstrated for rolofylline in the Prophylaxis for Thromboembolism in Critical Care Trial (PROTECT)-Pilot study, the larger PROTECT trial did not reach its primary endpoints and revealed higher incidence of seizure with a trend toward more occurrences of stroke. Research on rolofylline has been discontinued, said Marco Metra, MD, University of Brescia, Brescia, Italy, on September 1 at the 2009 Congress of the European Society of Cardiology (ESC). In the PROTECT-Pilot study, treatment with rolofylline 30 mg was associated with trends toward better symptom improvement, lesser worsening renal function, and fewer deaths or readmissions for heart failure or renal dysfunction over the next 60 days. In the larger PROTECT study, patients were randomised 2:1 to rolofylline 30 mg per day (n = 1,356) or placebo (n = 677) administered as a daily infusion for 4 hours daily for 3 days. The primary endpoint was a 3-way evaluation into categories of treatment success, patient unchanged, or treatment failure. Treatment success entailed moderate to markedly better dyspnoea at 24 and 48 hours after the start of study drug compared with baseline, in the absence of any other criteria for treatment failure. Among inclusion criteria were heart failure histories of at least 14 days duration (with diuretic therapy), hospitalisation for acute heart failure symptoms requiring intravenous diuretics with ongoing need anticipated for at least 24 hours, impaired renal function, and systolic blood pressure of >=95 mm Hg but <160 mm Hg at baseline. Analysis showed treatment success in 36.0% of patients in the placebo group and in 40.6% of the rolofylline group. Treatment failures were slightly higher in the rolofylline group (19.8% placebo vs 21.8% rolofylline). Dyspnoea improvement was found in 44.5% of patients in the placebo group and in 51.2% of patients in the rolofylline group. Persistent renal impairment was found more often in the rolofylline group (15.0%) than in the placebo group (13.7%; P = .441). Time to death or rehospitalisation for cardiovascular or renal symptoms was similar for both groups. Serious nervous system disorders (placebo [n = 4], rolofylline [n = 20]), seizures (placebo [n = 0], rolofylline [n = 11]), and strokes (ischaemic and haemorrhagic; placebo [n = 3], rolofylline [n = 16]) were all higher in the rolofylline group. Dr. Metra said that neither the primary nor secondary PROTECT endpoints were met, but that the overall safety profiles were similar without increases in cardiac adverse events for rolofylline. To a question posed at the official ESC press conference as to what was learned from PROTECT, Dr. Metra responded, “As frequently happens, successes in pilot studies are not replicated in large multicentre trials.” He said further that patients in [PROTECT-Pilot] receiving rolofylline did show some improvements in symptoms, but these were attended by important side effects.
[Presentation title: Effects of Rolofylline in Patients With Acute Heart Failure Syndrome and Renal Impairment: Findings From the PROTECT Study]
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