Efficacy of an Oral Prostacyclin Analog (Treprostinil Diethanolamine) in Patients with Advanced Lower Extremity Peripheral Arterial Disease and Ischemic Rest Pain

OBJECTIVES: Infused Treprostinil sodium, a prostacyclin analog has improved limb blood flow, reduced ischemic rest pain and promoted ischemic wound healing in patients with severe vascular disease in several studies. This study evaluates UT-15C (Treprostinil diethanolamine), a sustained release (SR) oral form of Treprostinil in patients with CLI (Fontaine IIIb-IVa) and ischemic lower limb rest pain.
METHODS: Eligible patients aged 45-85 years with Fontaine Stage III/IVa who required at least two weeks of analgesic therapy for ischemic rest pain, were given 2 mg BID of UT-15C SR for oral administration for 8 weeks. Ischemic rest pain was assessed using the Short Form McGill pain questionnaire (SF-MPQ), visual analog scale (VAS), and present pain intensity (PPI) scales along with analgesic use. Sleep interference was assessed using a visual analog scale in which patients rated their overall sleep for the past 2 weeks (0= excellent sleep, 10 =no sleep). Dosing was initiated at 1 mg QD and titrated weekly to the maximum dose (2mg BID). Follow-up values were compared to baseline values using the Wilcoxon signed rank test.
RESULTS: Eight out of 10 patients (mean age 72 years) completed study assessments. Mean baseline total SF-MPQ score was 19.4± 3.5 and decreased to 9.5 ± 2.7; p<0.01. Significant improvements from baseline to final assessment were observed in the VAS (4.7 ± 0.7 vs 1.5± 0.5; p=0.047) and sensory pain (16.4± 2.7 vs 8.4± 2.7; p<0.01) SF-MPQ scores. Although not significant, sleep interference VAS score decreased by 58% from 6.7 at baseline to 3.9 at final assessment, and PPI decreased from 2.9 to 1.8. Two adverse events were reported by two patients (mild headache and one episode of chills following the first dose).
CONCLUSIONS:The oral Prostacyclin analog Treprostinil diethanolamine was well-tolerated and associated with ischemic pain relief and improved sleep in patients with CLI. Patient outcomes at 2 mg BID are encouraging and suggest that a larger placebo-controlled trial is warranted.