A randomized phase II trial of Arginine Butyrate with standard local therapy in refractory sickle cell leg ulcers

P>Sickle cell leg ulcers are often debilitating, refractory to healing, and prone to recurrence. Healing of leg ulcers was incidentally observed during dose-ranging trials of Arginine Butyrate in beta haemoglobinopathies. Here, a controlled Phase II trial was performed in sickle cell patients who had lower extremity ulcers refractory to standard care for at least 6 months. Patients were randomized to receive standard local care alone (Control Arm) or standard care with Arginine Butyrate administered 5 d/week (Treatment Arm), for 12 weeks. Ulcers were photographed weekly, traced, and ulcer areas were calculated by computerized planimetry and compared between the two study arms. Twenty-seven study courses were evaluated. Control Arm subjects had 25 ulcers with a mean area of 25 center dot 7 cm2 initially and 23 center dot 2 cm2 after 12 weeks; 2/25 (8%) healed completely. Treatment Arm subjects had 37 ulcers with a mean area of 50 center dot 6 cm2 initially and 28 center dot 3 cm2 at 12 weeks; 11/37 of these (30%) healed completely. After 3 months, proportions of ulcers which healed were 6/25 (24%) and 29/37 (78%), in the Control and Treatment Arms respectively (P < 0 center dot 001). These findings strongly suggest that Arginine Butyrate merits further evaluation for the treatment of refractory sickle cell leg ulcers in larger trials.