Randomised controlled trial of aminosidine (paromomycin) v sodium stibogluconate for treating visceral leishmaniasis in North Bihar, India.
Jha TK., Olliaro P., Thakur CP., Kanyok TP., Singhania BL., Singh IJ., Singh NK., Akhoury S., Jha S.
OBJECTIVES:To assess the efficacy and tolerability of aminosidine compared with sodium stibogluconate for treating visceral leishmaniasis. DESIGN:Randomised, unblinded, controlled trial with 180 day follow up. SETTING:Kala-Azar Research Centre, Brahmpura, Muzaffarpur, Bihar, India. SUBJECTS:People of either sex aged 6-50 years with symptoms and signs suggestive of visceral leishmaniasis (fever, loss of appetite, enlarged spleen) with leishmania amastigotes detected in Giemsa stained aspirates of spleen or bone marrow. INTERVENTIONS:Aminosidine at three daily doses (12, 16, and 20 mg/kg) for 21 days and sodium stibogluconate 20 mg/kg/day for 30 days. MAIN OUTCOME MEASURES:Laboratory measures of efficacy: parasite count, haemoglobin concentration, white cell count, platelet count, serum albumin concentration. Clinical measures of efficacy: spleen size, fever, body weight, and liver size. Measures of safety: liver and renal function tests, reports of adverse events. RESULTS:Of the 120 patients enrolled (30 per treatment arm), 119 completed treatment and follow up. Cure at end of follow up was achieved in 23 (77%), 28 (93%), and 29 (97%) patients treated with 12, 16, and 20 mg aminosidine/kg/day respectively, and in 19 (63%) patients given sodium stibogluconate. At 16 and 20 mg/kg/day, aminosidine was significantly more active than sodium stibogluconate in both clinical and laboratory measures of efficacy. No significant clinical or laboratory toxicity occurred in any treatment group. CONCLUSIONS:A 21 day course of aminosidine 16 or 20 mg/kg/day should be considered as first line treatment for visceral leishmaniasis in Bihar.