A prospective randomized, comparative, open-label trial of the safety and efficacy of paromomycin (aminosidine) plus sodium stibogluconate versus sodium stibogluconate alone for the treatment of visceral leishmaniasis

Response to treatment with organic pentavalent antimonials, the standard first-line treatment for visceral leishmaniasis (VL), has been decreasing since their introduction into India. Combining sodium stibogluconate (SB) with paromomycin (PM) may be an efficient alternative to single-agent therapy. This trial was designed to assess the safety and efficacy of PM 12 or 18 mg/kg daily plus SE 20 mg/kg daily for 21 days compared to SE alone for 30 days. One hundred and fifty patients were randomly assigned in 1996 to 1 of the 3 treatments and followed-up for 180 days. At the end of treatment, 49 of 52 patients receiving PM12+SB, 46 of 48 receiving PM18+SB, and 27 of 49 patients receiving SE alone, were cured. During follow-up there was 1 relapse in each of the treatment groups, giving final cure rates of 48 of 52 (92.3%) for PM12+SB, 45 of 48 (93.8%) for PM18+SB, and 26 of 49 (53.1%) for SE. PM plus SE for 21 days at either 12 or 18 mg/kg daily was significantly more effective than SE alone for 30 days (chi(2) P < 0.001). One patient (SB alone) had experienced a serious adverse event: cardiotoxicity at day 8 (myocarditis and ECG changes) which caused withdrawal from the study. Only 19 of 100 patients enrolled in the PM treatment arms had a complete audiogram series conducted thus making it difficult to assess oto-toxicity. PM 12 or 18 mg/kg daily plus a standard dose of SE for 21 days was statistically more effective than SE in producing a final cure for patients with VL in Bihar, India.