The purpose of this study was to assess the safety of continuous subcutaneous
therapy with
treprostinil sodium (
Remodulin), a
prostacyclin analog, and its effect on ischemic rest
pain and ischemic wound healing in subjects with
critical limb ischemia (CLI) and no planned revascularization procedure. This was a 12-week, open-label, single-center pilot study enrolling 10 subjects (mean age 82.4 years) with Fontaine stage III to IV (Rutherford class 4-6)
peripheral arterial disease and ankle brachial indices less than 0.55. The primary end point was safety, and the secondary end points were the effects of treatment on ischemic rest
pain,
limb salvage, and wound healing. There was a 62% reduction in mean worst rest
pain and a 57% reduction in mean average rest
pain at week 12, with most subjects using less
pain medication. Three subjects experienced complete healing of their
wounds. No subject developed a new
wound during the trial.
Treprostinil was generally well tolerated.
Subcutaneous infusion-site
pain was the most frequently reported side effect, with one subject withdrawing from the study as a result. Jaw
pain was reported by two subjects. One subject experienced two serious adverse events considered unrelated to
treprostinil (
cholecystitis and
congestive heart failure). This study demonstrates that chronic, continuous subcutaneous
treprostinil is safe and can be useful in the treatment of ischemic
pain and
wounds in subjects with CLI. Future controlled studies are needed to evaluate these effects and determine appropriate patient selection.