Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication

Prostacyclin is an endothelially derived vasodilator and inhibitor of plate let aggregation. Despite its therapeutic potential for peripheral arterial disease, the short half-life and chemical instability are barriers to routi ne therapy. Accordingly, prostacyclin analogs are being evaluated in patien ts with peripheral arterial disease. State-of-the-art non-invasive ultrason ography allows for serial testing of the hemodynamic effects of vasoactive drugs. The safety, efficacy and hemodynamic effects of UT-15, a novel, long -acting prostacyclin analog, were studied in patients with severe intermitt ent claudication. A total of eight patients with stable severe intermittent claudication, Fontaine classes IIb-III, were admitted to the hospital for intravenous infusion of UT-15. A symptom-limited, dose-escalation protocol was instituted, beginning with placebo and then with increasing dosage at 6 0-min intervals, followed by a 2-h period of maintenance dose at the maximu m well-tolerated infusion rate. The hemodynamic response in the lower limbs was assessed with serial ultrasonography, segmental arterial pressures and pulse volumes. Blood flow in the common femoral artery increased 29% (p= 0 .003) by the end of the maintenance period and remained above baseline thro ughout the washout period (p= 0.044). Blood velocity in the lower limb incr eased in most of the peripheral arteries. These increases achieved statisti cal significance in the common femoral artery (p = 0.025) and anterior tibi al artery (p = 0.019), and approached significance in the popliteal artery (p =0.062). In two of four patients in whom blood flow was undetectable bef ore the infusion, arterial blood flow at the ankle level became apparent on ultrasonography during maintenance infusion. UT-15 infusion improved the p ulse volume recording (p = 0.016) but the ankle/brachial index did not chan ge significantly. Common side effects at peak dose included headache and na usea. There were no serious adverse events attributable to UT-15 treatment. In most patients, the optimal infusion rate was 10-20 ng/kg per min. In co nclusion, ultrasonography is a novel approach for assessing the hemodynamic response to vasoactive agents. UT-15 is well tolerated when given for up t o 2 h and increases arterial blood flow and velocity in patients with sever e intermittent claudication.