A randomized phase II trial of Arginine Butyrate with standard local therapy in refractory sickle cell leg ulcers.
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 25·7 cm(2) initially and 23·2 cm(2) after 12 weeks; 2/25 (8%) healed completely. Treatment Arm subjects had 37 ulcers with a mean area of 50·6 cm(2) initially and 28·3 cm(2) 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 < 0·001). These findings strongly suggest that Arginine Butyrate merits further evaluation for the treatment of refractory sickle cell leg ulcers in larger trials.
McMahon
Lillian
L
Cancer Center and Hemoglobinopathy Thalassemia Research Unit, Boston University School of Medicine, Boston, MA 02118, USA.
Tamary
Hannah
H
Askin
Melissa
M
Adams-Graves
Patricia
P
Eberhardt
Robert T
RT
Sutton
Millicent
M
Wright
Elizabeth C
EC
Castaneda
Serguei A
SA
Faller
Douglas V
DV
Perrine
Susan P
SP
D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications*; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002087:Butyrates / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007871:Leg Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects; D055815:Young Adult
D002087:Butyrates; D001120:Arginine; C033018:arginine butyrate