Acute effect of NKH477, a novel forskolin derivative, in patients with acute heart failure: A multicenter placebo-controlled double-blind trial

We conducted a multicenter two-stage randomized double-blind placebo- controlled study to assess the efficacy and safety of NKH477. This drug, a newly synthesized water-soluble forskolin derivative, has been previously shown to improve hemodynamics and subjective symptoms in patients with acute heart failure. In the first stage (study 1), 62 patients with acute heart failure were randomly assigned to receive either NKH477 by intravenous administration at 0.5 μg/kg/min for 30 min or a lower dose of NKH477 as a 'substitute' placebo, namely 0.2 μg/kg/min for 30 min. The second stage (study 2) began within 10 min after the end of dosing in study 1. Thirty-six patients were randomly assigned to either continue treatment with NKH477 at 0.5 μg/kg/min for 1 hr or to receive matching vehicle placebo. In study 1, the percentage improvement in hemodynamic and subjective and objective conditions in the control group as judged by attending physicians was 25.7 %. In contrast, improvement in the NKH477 group was 70.4 %, this difference being significant (p<0.01). No significant difference was seen between the groups with respect to side effects and abnormal changes in laboratory data. Usefulness as rated according to the above assessment was 23.3 % in the lower dose group and 70.4 % in the NKH477 group, this difference again being significant (p<0.01). Moreover, in study 2, the percentage improvement was even greater in the NKH477 group compared to the placebo group, at 83.3 % and 8.3 %, respectively. Again, there was no significant difference between the groups with respect to side effects and abnormal changes in laboratory data. Respective usefulness values were 75.0 % and 8.3 %, this difference again being significant (p<0.01). These results indicate that NKH477 is useful and safe in the treatment of acute heart failure.