Intermittent intravenous urokinase for critical limb ischemia in diabetic foot ulceration

Matthias Weck; Hannes Rietzsch; Holger Lawall; Uwe Pichlmeier; Peter Bramlage; Sebastian Schellong

doi:10.1160/TH08-02-0110

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(03): 475-482
DOI: 10.1160/TH08-02-0110

Wound Healing and Inflammation / Infection

Schattauer GmbH

Intermittent intravenous urokinase for critical limb ischemia in diabetic foot ulceration

Matthias Weck

¹Clinic Bavaria, Dept. Diabetes, Metabolism and Endocrinology, Kreischa, Germany

²Diabetic Foot Unit, Freital Hospital, Freital, Germany

,

Hannes Rietzsch

³Medical Clinic III, Technical University Dresden, Germany

,

Holger Lawall

⁴Department of Internal Medicine/Vascular Medicine, Hospital Karlsbad-Langen-steinbach, University of Heidelberg, Karlsbad, Germany

,

Uwe Pichlmeier

⁵Medac GmbH, Wedel, Germany

,

Peter Bramlage

⁶Institute for Clinical Pharmacology, Technical University Dresden, Germany

,

Sebastian Schellong

³Medical Clinic III, Technical University Dresden, Germany

› Author Affiliations

Abstract

Summary

Patients with diabetic foot ulceration and critical limb ischemia have a high risk of major amputation, especially if limbs can not be revascularized. Urokinase is effective in improving microcirculation in critical limb ischemia and might improve outcomes. There are no data on the efficacy and safety of urokinase treatment (survival free of major amputation, ulcer healing and the rate of minor and major bleeding). Therefore, we aimed to investigate the effect of urokinase treatment in a phase II clinical trial. We performed an open, prospective, non-controlled, multi-center phase II cohort study in 77 type-2 diabetic patients with critical limb ischemia and diabetic foot ulceration. Patients had no surgical or endovascular treatment option based on interdisciplinary consensus. Urokinase (1 Mio IU if plasma fibrinogen ≥2.5 g/l, 0.5 Mio IU if fibrinogen < 2.5 g/l) was administered for 21 days as an intravenous infusion over 30 minutes. Each patient was followed up for 12 months. Treatment for a median of 21 days resulted in 33% of patients being alive, having no major amputation and completely healed ulcers after 12 months. Total survival rate was 84.6%,amputation-free survival 69.2% and rate of major amputation 21.1%.Eighty-two percent of patients experienced at least once a complete ulcer healing within the course of study. Three serious adverse events were urokinase-related. Urokinase treatment in diabetic patients with critical limb ischemia appears to be effective, feasible and safe. Although this calls for a larger, randomized and controlled trial, the results are highly relevant for clinical practice to prevent these patients from receiving major amputation due to diabetic foot syndrome.

Clinical Trial Registration No.: NCT00537498

Keywords

Urokinase - critical limb ischemia - diabetic foot syndrome - peripheral arterial disease - revascularization

Full Text

References

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