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Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication.
Vasc Med. 2000; 5(4):231-7.VM

Abstract

Prostacyclin is an endothelially derived vasodilator and inhibitor of platelet aggregation. Despite its therapeutic potential for peripheral arterial disease, the short half-life and chemical instability are barriers to routine therapy. Accordingly, prostacyclin analogs are being evaluated in patients with peripheral arterial disease. State-of-the-art non-invasive ultrasonography 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 intermittent 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 60-min intervals, followed by a 2-h period of maintenance dose at the maximum 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 throughout the washout period (p = 0.044). Blood velocity in the lower limb increased in most of the peripheral arteries. These increases achieved statistical significance in the common femoral artery (p = 0.025) and anterior tibial 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 before the infusion, arterial blood flow at the ankle level became apparent on ultrasonography during maintenance infusion. UT-15 infusion improved the pulse volume recording (p = 0.016) but the ankle/brachial index did not change significantly. Common side effects at peak dose included headache and nausea. 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 conclusion, ultrasonography is a novel approach for assessing the hemodynamic response to vasoactive agents. UT-15 is well tolerated when given for up to 2 h and increases arterial blood flow and velocity in patients with severe intermittent claudication.

Authors+Show Affiliations

Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11213235

Citation

Mohler, E R., et al. "Trial of a Novel Prostacyclin Analog, UT-15, in Patients With Severe Intermittent Claudication." Vascular Medicine (London, England), vol. 5, no. 4, 2000, pp. 231-7.
Mohler ER, Klugherz B, Goldman R, et al. Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication. Vasc Med. 2000;5(4):231-7.
Mohler, E. R., Klugherz, B., Goldman, R., Kimmel, S. E., Wade, M., & Sehgal, C. M. (2000). Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication. Vascular Medicine (London, England), 5(4), 231-7.
Mohler ER, et al. Trial of a Novel Prostacyclin Analog, UT-15, in Patients With Severe Intermittent Claudication. Vasc Med. 2000;5(4):231-7. PubMed PMID: 11213235.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trial of a novel prostacyclin analog, UT-15, in patients with severe intermittent claudication. AU - Mohler,E R,3rd AU - Klugherz,B, AU - Goldman,R, AU - Kimmel,S E, AU - Wade,M, AU - Sehgal,C M, PY - 2001/2/24/pubmed PY - 2001/6/8/medline PY - 2001/2/24/entrez SP - 231 EP - 7 JF - Vascular medicine (London, England) JO - Vasc Med VL - 5 IS - 4 N2 - Prostacyclin is an endothelially derived vasodilator and inhibitor of platelet aggregation. Despite its therapeutic potential for peripheral arterial disease, the short half-life and chemical instability are barriers to routine therapy. Accordingly, prostacyclin analogs are being evaluated in patients with peripheral arterial disease. State-of-the-art non-invasive ultrasonography 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 intermittent 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 60-min intervals, followed by a 2-h period of maintenance dose at the maximum 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 throughout the washout period (p = 0.044). Blood velocity in the lower limb increased in most of the peripheral arteries. These increases achieved statistical significance in the common femoral artery (p = 0.025) and anterior tibial 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 before the infusion, arterial blood flow at the ankle level became apparent on ultrasonography during maintenance infusion. UT-15 infusion improved the pulse volume recording (p = 0.016) but the ankle/brachial index did not change significantly. Common side effects at peak dose included headache and nausea. 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 conclusion, ultrasonography is a novel approach for assessing the hemodynamic response to vasoactive agents. UT-15 is well tolerated when given for up to 2 h and increases arterial blood flow and velocity in patients with severe intermittent claudication. SN - 1358-863X UR - https://www.unboundmedicine.com/medline/citation/11213235/Trial_of_a_novel_prostacyclin_analog_UT_15_in_patients_with_severe_intermittent_claudication_ L2 - https://www.lens.org/lens/search?q=citation_id:11213235 DB - PRIME DP - Unbound Medicine ER -