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Dianne Zwicke, MD; Brian Buggy, MD; Don Lobacz, MD; Wendy Schmidt, RN; Karen Harris, RN; Michael Wade, PhD; Kristan Rollins, PharmD; Deborah Strootman, RN, BSN, Aurora St. Luke's Medical Center, University of Wisconsin School of Medicine and Public Health-Milwaukee Clinical Campus, Milwaukee, Wis; United Therapeutics Inc., Silver Springs, Md
Background: Refractory critical limb ischemia (CLI) results in loss of limbs and digits regardless of etiology. Prostacyclin (PGI2) and its analogs have been proposed as a pharmacologic therapy. Treatment with the prostacyclin analog treprostinil sodium* has been shown to improve blood flow in the legs of patients with severe vascular disease.
Methods: Twelve weeks of treatment with treprostinil*(continuous subcutaneous infusion) in an open label trial showed encouraging results on ischemic pain (visual analog scale and medication usage) and wound healing in adults with CLI. Eight of these subjects have entered into a 12-week extension study to determine whether additional treatment would be beneficial; both trials are ongoing
Results: Further improvement of the wounds occurred with additional treatment and continued escalation of the treprostinil dose. Four subjects completed an additional 12 weeks of treprostinil therapy, 2 subjects withdrew due to side effects, 1 subject with progressive CHF withdrew for end of life planning, and 1 subject withdrew when wounds improved. Three subjects had complete healing. All subjects reported continued pain relief, with 3 patients discontinuing narcotic pain medications. One subject had digital ischemic lesions recur. Mean peak dose of treprostinil was 24 ng/kg/min. Side effects were manageable and included subcutaneous infusion site pain, jaw pain, headache, and diarrhea.
Conclusions: Treprostinil sodium* appears to contribute to wound healing and relieve ischemic pain in the presence of CLI. Previous studies have limited the duration of therapy to 12 weeks and doses were limited to 15 ng/kg/min. The preliminary results of this extension study suggest that treatments with higher doses and longer durations may increase the benefit of treprostinil in patients with CLI.
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