Rationalisation of regimens of treatment of kala-azar with sodium stibogluconate in India: a randomised study.

The efficacy and safety of six regimens of treatment for kala-azar (visceral leishmaniasis) with sodium stibogluconate were evaluated in a prospective randomised study to ascertain the optimal treatment for Indian patients. Altogether 371 patients with kala-azar were randomised to receive sodium stibogluconate intramuscularly at a dose of 10 mg/kg body weight/day for 20 or 40 days (groups A and A1, respectively), 15 mg/kg body weight/day for 20 or 40 days (groups B and B1, respectively), or 20 mg/kg body weight/day for 20 or 40 days (groups C and C1, respectively). Patients were examined blind before and at the end of treatment and every month for six months. The number of patients who were apparently cured--that is, those whose temperature had returned to normal at the end of their regimen of treatment--was 45 (78%) in group A, 53 (87%) in group A1, 50 (81%) in group B, 60 (95%) in group B1, 58 (92%) in group C, and 62 (97%) in group C1. At six months 62 patients (97%) in group C1, 51 (81%) in group C, 54 (86%) in group B1, 42 (68%) in group B, 45 (74%) in group A1, and 33 (57%) in group A had not relapsed and were cured as confirmed by a bone marrow aspirate free of parasites. The differences between groups C1 and C, B1 and B, and A1 and A were significant. Logistic regression of the proportion cured with the dose and length of treatment showed that both factors were significant in improving the rate of cure; the highest dose for the longer time (group C1) had the best rate of cure. One patient in group C1, 12 in group C, nine in group B1, 18 in group B, 15 in group A1, and 23 in group A were cured with extended courses of 20 mg sodium stibogluconate. One patient in each of groups C1, B, A1, and A became unresponsive to antimony and were cured with pentamidine. One patient in each of groups C1, B, and A became unresponsive to both antimony and pentamidine. The patients tolerated the longer duration of treatment safely, and side effects were minor. Sodium stibogluconate should be given intramuscularly in the dosage of 20 mg/kg for at least 40 days, when patients should be assessed for further treatment if necessary. Such a regimen should achieve the highest rate of cure with low toxicity and low rates of relapse and unresponsiveness.