Aminosidine plus sodium stibogluconate for the treatment of Indian kala-azar: a randomized dose-finding clinical trial

Abstract

This randomized, open sequential design trial was set up to assess the efficacy, tolerability and toxicity of 20 d courses of combined intramuscular aminosidine and sodium stibogluconate at various dosages in patients with newly-diagnosed kala-azar in Bihar, India. Three successive studies of 96 patients each were originally planned with aminosidine administered at 12, 6 and 3 mg/kg/d, respectively. For each aminosidine dosage, patients were randomly assigned to receive sodium stibogluconate at 20, 10 or 5 mg/kg/d of antimony. Ninety-six patients were enrolled and assigned aminosidine 12 mg/kg/d as scheduled. In the subsequent study with aminosidine at 6 mg/kg/d, the trial was interrupted after 40 patients had entered owing to inadequacy of the treatment. With aminosidine 12 mg/kg/d the success rates with sodium stibogluconate at 20, 10 and 5 mg/kg/d were 88%, 71% and 72%, respectively and did not differ significantly. With aminosidine 6 mg/kg/d, 69%, 50% and 46% of patients were cured with the same sodium stibogluconate doses, respectively; again, there was no significant difference between the subgroups. The overall success rate with aminosidine at 12 mg/kg/d (76%) was significantly higher than that with 6 mg/kg/d (55%) (odds ratio = 2.69; 95% confidence interval, 1.11-6.4). Patients improved clinically and the treatments were equally well tolerated. The combination of aminosidine 12 mg/kg/d and sodium stibogluconate 20 mg/kg/d for 20 d appears to be an effective and safe replacement in Bihar for sodium stibogluconate alone for > or = 40 d.