Abstract 12341: Evaluation of Trans Sodium Crocetinate on Safety and Exercise Performance in Patients with Peripheral Artery Disease and Intermittent Claudication
Background: Trans sodium crocetinate (TSC) is a synthetic carotenoid that improves the diffusion of oxygen in animal models of hypoxia and ischemic disease. This clinical study tested the hypotheses that multiple doses of TSC are safe in PAD and a preliminary dose-response relationship could be identified as increased peak walking time (PWT).
Methods: Forty-eight patients with symptomatic PAD and an ankle-brachial index < 0.90 were included, while critical limb ischemia, recent revascularization, and exercise limited by symptoms other than claudication were exclusionary. Eight dosing levels of TSC were evaluated ranging from 0.25 mg/kg to 2.0 mg/kg (5 patients/dose) and 8 patients were randomized to placebo (saline). Blinded study medication was given intravenously once daily for 5 days. Subjects were tested on a graded treadmill protocol to claudication-limited PWT at baseline, after the first and fifth doses, and 5 days after completion of dosing. Changes in log-transformed PWT from baseline to Day 5 (primary) were fit with a cubic regression to detect a prespecified inverted U-shaped dose-response relationship at the upper end of dosing with only 65% power to detect this response. Patient-reported change in walking distance from the Walking Impairment Questionnaire was a secondary endpoint.
Results: Patient demographics were well balanced among dose groups. Adverse events were not predominant on any drug dose relative to placebo. Changes in PWT demonstrated a cubic trend for dose (p=0.07, r=0.39, r2=0.15) with morphologic signals of benefit at doses above 1.00 mg/kg at both the first and fifth dosing days. Similar improvements occurred with the walking distance score at doses above 1.00 mg/kg.
Conclusions: TSC was safe and well tolerated at all doses. Notable signals of benefit were observed at higher doses for both PWT and patient-perceived walking distance. These results support a phase II study to define the optimal dose for longer term therapy with TSC.
- © 2010 by American Heart Association, Inc.