BACKGROUND: Beraprost sodium (BPS) is a new stable, orally active prostaglandin I2 analogue with antiplatelet and vasodilating properties. It has been widely used for the treatment of pulmonary hypertension and atherosclerotic peripheral arterial disease (PAD), but its efficacy in peripheral microvascular dysfunction has not been established. We designed a placebo-controlled, double-blind, randomized trial of BPS in patients with symptom of microvascular dysfunction in high-risk diabetic patients, and report the results of the interim analysis.
METHODS: In this placebo-controlled, double-blind, randomized trial (conducted from Oct 2009 to May 2010), 46 patients (male 33%, 60 ± 6 years) with symptoms of microvascular dysfunction but without evidence of PAD were randomized to receive BPS (40 microgram, tid) or placebo for 8 weeks. Blood was sampled for routine chemistry at baseline and at 8 weeks. All patients underwent temperature rebound (TR) and nadir to peak (NP) as an objective index of vascular reactivity using digital thermal monitoring device (Vendys, Endothelix Inc., Houston). Intensity and frequency of symptoms – pain, burning sensation, paresthesia and numbness - were recorded as a subjective index at inclusion and at the end of the study. The primary end point was the improvement of total symptom score (TSS), TR and NP above baseline.
RESULTS: At 8 weeks of treatment, the change of TR, NP and TSS did not reach statistical significance of differences between BPS and placebo (TR: 0.13 ± 0.63 vs. 0.22 ± 0.67 °C, p=0.62; NP: 0.57 ± 0.80 vs. 0.59 ± 0.60 °C, p=0.90; TSS: 2.43 ± 2.23 vs. 3.24 ± 2.70 points, p=0.29). The number of patients who showed an improvement of TR (8 vs. 11, p=0.226), NP (14 vs. 21, p=0.170), and TSS (16 vs. 21, p=0.506) was also similar between BPS and placebo.
CONCLUSION: The BPS did not reach statistically significance in both subjective symptoms and objective parameters. The beneficial effects of beraprost on symptomatic microvascular dysfunction in high-risk diabetic patients should be confirmed in long-term large clinical trials.
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