Background: The aim of the present study was to assess the safety and tolerability of the controlled-release (CR) formulation of the β-blocker carvedilol in Japanese patients with chronic heart failure (HF).
Methods and results: In this multicenter, randomized, open-label, phase I/II dose-escalation study, 41 patients receiving standard therapy for chronic HF were randomized in a ratio of 1:1 to carvedilol CR or immediate-release (IR) carvedilol. The primary objective was to evaluate the tolerability and safety of escalating doses of carvedilol CR (10-40 mg/day), with a reference arm of 5-20 mg/day of carvedilol IR. In addition, the tolerability and safety of titration to a carvedilol CR dose up to 80 mg/day were examined, as were plasma concentrations of carvedilol and changes in vital signs. The proportions of patients who completed 40-mg/day carvedilol CR and 20-mg/day carvedilol IR were 42% (8/19) and 50% (11/22), respectively. In the CR group, 7/19 (37%) attained a dose of 80 mg. During the primary evaluation period, 7/19 (37%) and 4/22 (18%) patients experienced drug-related adverse events in the CR and IR groups, respectively, the characteristics of which were similar between groups.
Conclusions: No new safety issues emerged in Japanese chronic HF patients treated with carvedilol CR in contrast to those known in carvedilol IR.
Trial registration: ClinicalTrials.gov NCT00742508.