Parenteral therapy with lipo-ecraprost, a lipid-based formulation of a PGE1
analog, does not alter six-month outcomes in patients with critical leg ischemia.
Author(s): Brass EP, Anthony R, Dormandy J, Hiatt WR, Jiao J, Nakanishi A, McNamara T,
Nehler M; Circulase investigators.
Affiliation(s): Harbor-UCLA Medical Center for Clinical Pharmacology, Torrance, California 90502,
USA. ebrass@ucla.edu
Publication date & source: 2006, J Vasc Surg. , 43(4):752-9
PURPOSE: Eicosanoids with vasodilating and angiogenic properties have been
postulated to be effective therapies for critical leg ischemia (CLI) secondary to
atherosclerotic peripheral arterial disease. The ability to deliver active drug
to the site of action at adequate doses for sufficient duration has been a major
limitation in the clinical development of such therapies. Lipo-ecraprost is a
lipid-encapsulated prostaglandin E1 prodrug with the potential to deliver active
prostaglandin to the site of critical arterial ischemia. The current trial was
designed to test the hypothesis that lipo-ecraprost would improve amputation-free
survival in patients with CLI who had no revascularization options.
METHODS: The study was randomized, multicenter, double blind, and placebo
controlled. Patients who met clinical and hemodynamic criteria were randomized to
receive placebo or lipo-ecraprost (60 microg) administered intravenously on each
of 5 days per week, for a total of 8 weeks. The study's primary endpoint was the
rate of a composite end point of death or amputation above the level of the ankle
at 180 days (6 months).
RESULTS: The study was terminated on a recommendation from the Data and Safety
Monitoring Board after the completion of a protocol-specified interim analysis
for futility. At the time of termination, 383 of the planned 560 patients had
been randomized, of which 379 received at least one dose of study medication and
thus were included in the intention-to-treat population. Twenty-three patients
were lost to follow-up and were not available for 6-month assessments. At 6
months of follow-up, there were 23 amputations in the 177 patients who received
placebo, and 29 amputations in the 179 patients randomized to lipo-ecraprost. At
6 months, 10 deaths had occurred in the placebo group and 18 deaths had occurred
in the lipo-ecraprost arm. Changes in lower-extremity hemodynamics over the
6-month study period did not differ between the placebo and lipo-ecraprost
treatment arms.
CONCLUSION: Intensive treatment with lipo-ecraprost failed to modify the 6-month
amputation rate in patients with CLI who were not candidates for
revascularization.
|