Adjunctive parenteral therapy with lipo-ecraprost, a prostaglandin E1 analog, in patients with critical limb ischemia undergoing distal revascularization does not improve 6-month outcomes.

ABSTRACT

PURPOSE: In patients with critical limb ischemia (CLI), distal revascularization remains the procedure of choice for preventing limb loss, but long-term outcomes for pain relief, wound healing, and prevention of amputation remain suboptimal. Prostaglandin drug therapy as an adjuvant to revascularization may improve these outcomes. The current trial was designed to test the hypothesis that the use of lipo-ecraprost, a lipid encapsulated prostaglandin E(1) prodrug, as an adjunctive therapy after distal revascularization would improve amputation-free survival in patients with CLI. METHODS: The study was randomized, multicenter, double blind, and placebo controlled. Patients meeting clinical and hemodynamic criteria for CLI who were undergoing either bypass or endovascular revascularization of the below knee popliteal or more distal arteries were randomized to receive placebo or a 60-microg dose of lipo-ecraprost administered intravenously starting death or amputation at or above the level of the ankle at 180 days.

RESULTS:

The study randomized 322 patients, and 284 received at least one dose of study medication and were included in the intention-to-treat population. A total of 213 patients underwent surgical bypass, and 71 underwent endovascular revascularization before receiving study medication. The distribution of index revascularization procedures and location of distal target arteries were similar for both placebo and lipo-ecraprost groups. At 180 days, 21 patients (7.4%) were lost to follow-up before reaching the primary end point. Seventy-one percent of the patients taking the placebo completed at least half the doses of the study medication compared with 48% of those taking lipo-ecraprost. Index leg revascularization-assisted primary patency was 82% in the placebo group and 84% in the lipo-ecraprost group (P = .874). Changes in lower extremity hemodynamics as a result of the revascularization during the study period did not differ between the placebo and lipo-ecraprost treatment arms. For the primary event of amputation-free survival, there were no differences between groups 19 major amputations occurred in the placebo group and 17 in the lipo-ecraprost group; 19 deaths occurred in the placebo group and 13 in the lipo-ecraprost group.

CONCLUSION:

Eight weeks of parenteral therapy with lipo-ecraprost after distal revascularization in patients with CLI provided no additional benefit in the reduction of major amputation or death at 180 days.