55 research outputs found
Rationale, design, and results from RENO-DEFEND 1: A randomized, dose-finding study of the selective A1 adenosine antagonist SLV320 in patients hospitalized with acute heart failure
Background Baseline renal impairment as well as worsening renal function
during hospitalization is associated with worse short-and long-term
outcomes in patients hospitalized for acute heart failure (AHF). We
hypothesized that selective A1 adenosine receptor blockade would induce
natriuresis while preserving renal function in AHF patients with renal
dysfunction.
Methods A phase II, randomized, double-blind, placebo-controlled,
parallel group, multicenter study to evaluate the efficacy and safety of
2.5, 7.5, 15, and 30 mg/d SLV320 (1 hour intravenous infusions of 1.25,
3.75, 7.5, and 15 mg SLV320, every 12 hours for 3 days [a total of 6
doses] in addition to standard therapy) in subjects hospitalized with
AHF and renal impairment who meet all inclusion/exclusion criteria. The
study planned to enroll 450 subjects, with 90 subjects allocated equally
to each treatment arm.
Results The study was terminated early. The decision, which was
unrelated to the study conduct or results, with a total of 46 subjects
randomized. Of those randomized, 6: 8: 8: 8 and 6 patients,
respectively, completed the study in each of the dosing subgroups, with
placebo as the fifth group. For the 1.25-mg study group, the mean age
was 73 years; mean (SD) systolic blood pressure (SBP), 128.5 (16.2);
heart rate, 80.8 (25.0); brain natriuretic peptide, 969.7 (571.28);
creatinine (mu mol/L), 149.7 (41.0); cystatin C, 1.468 (0.2777);
estimated glomerular filtration rate, 33.8 (7.913); and blood urea
nitrogen, 12.1 (2.9), with roughly similar values in each treatment arm.
No seizures were reported during the study. Eight patients died during
the study, none of whom were associated with the study drug per an
independent, blinded, data safety monitoring board.
Conclusion Because of the limited number of subjects and variability
observed in the results, no definite conclusions can be made regarding
the efficacy and safety of SLV320. (Am Heart J 2011;161:1012-1023.e3.
- …