Double-blind crossoer clinical trial of pyridinolcarbamate in peripheral arterial disease (arteriosclerosis obliterans).

Abstract

A double-blind crossover clinical trial of pyridinolcarbamate, a bradykinin antagonist, was carried out in 33 men with peripheral vascular disease causing intermittent claudication. Results in 25 men are reported.Peripheral circulation was assessed by measurement ofwork done before claudication in a step test, claudication point, and measurement of cal bloodflow by venous occlusion plethysmography before and after exercise in a temperature-controlled environment. Performance in all three tests decreased during the placebo control period, making the evaluation of treatment difficult. During the trial a significant improvement occurred in the step test. No dose-related drug effect was shown but a cumulative drug effect could not be decisively excluded. Performance in the step test correlated with alteration of external environmental temperature. Claudication point showed some improvement but only analysis over time produced a value significantly differentfrom the combined control. Calf blood-flow increased to a small extent over treatment and time but did not exceed control values sgnificantly.The possible role of bradykinin in peripheral vascular disease in relation to the rationale of treatment with pyridinolcarbamate and the possibility of a seasonal variation in sensitivity to bradykinin (to account for the findings noted) are discussed.