DOUBLE-BLIND PLACEBO-CONTROLLED CROSSOVER STUDY OF ORAL NICARDIPINE IN THE TREATMENT OF RAYNAUDS-PHENOMENON

The purpose of this study was to measure the efficacy and side effects of oral nicardipine in the treatment of Raynaud's phenomenon (RP). The study consisted of a 3-week baseline period followed by a double-blind, randomized, two-period placebo-controlled, balanced crossover design. Both treatment periods of 3 weeks with either oral nicardipine (3 x 30 mg) or matching placebo were interrupted by a 2-week washout period. Twenty-five patients with either primary (n = 16) or secondary (n = 9) RP participated. Twelve of them had taken part in a previous study on the acute effects of i.v. nicardipine to find out whether long-term efficacy could be predicted by the acute circulatory effects. No statistically significant differences were found between nicardipine and placebo for number, duration, or severity of vasospastic attacks or for any of the microcirculatory parameters (finger skin temperature and laser Doppler- flux) measured during a finger cooling test. In patients with primary RP, heart rate significantly increased during nicardipine treatment (mean +/- SD: 9 +/- 6 beats/min; p < 0.05). The long-term effects could not be predicted by the outcome of the i.v. study. Plasma nicardipine concentrations varied considerably, but in general were on the low side (17.4 +/- 3.7 ng/ml; range, 0-55.4 ng/ml). The adverse effects reported with nicardipine were similar to those with placebo, and required withdrawal of two patients on nicardipine and one on placebo. In conclusion, the results show that oral nicardipine does not significantly alter the course of RP. This is in contrast to a previous study with i.v. nicardipine in which the microcirculatory measurements improved significantly. A possible explanation is the lower plasma nicardipine concentrations obtained during the oral study. However, as the daily dose of nicardipine was already 90 mg, a higher dose could have substantially increased the frequency and severity of side effects.