BACKGROUND: In Bihar, India, where visceral leishmaniasis (VL) is hyperendemic and refractory to antimony, amphotericin B is the most effective option for the treatment of VL. Lipid formulations of amphotericin B are able to circumvent the toxic effect of conventional amphotericin B, and the total dose of these formulations can be administered over a short duration. However, cost is a major constraint in the use of lipid formulations of amphotericin B. Amphotericin B colloidal dispersion (ABCD), which is a less expensive lipid formulation, has not been tested for the treatment of VL in India. METHODS: In an open-label, randomized clinical trial, we evaluated the efficacy and safety of a 6-day course of ABCD administered to 3 different dose groups (total dose: 7.5 mg/kg [group A], 10 mg/kg [group B], and 15 mg/kg [group C]), each of which included a cohort of 135 patients. RESULTS: Although infusion-related fever and chills occurred in 56%-68% of patients in the 3 different dose groups, 401 of 405 patients completed the treatment. All 135 patients in group A completed treatment, and the final cure rate for this group was 97%. In the group that received the highest dose of ABCD (group C), severe backache, an unusual side effect, was observed in 8 patients (5.92%). Serious adverse effects led to the withdrawal of 2 patients (1.48%) each from group B and group C. CONCLUSIONS: Although the cost of ABCD is prohibitive, the high level of efficacy associated with short-term treatment with low-dose ABCD provides another alternative for the treatment of VL, especially in regions where VL is antimony refractory.
RCT Entities:
BACKGROUND: In Bihar, India, where visceral leishmaniasis (VL) is hyperendemic and refractory to antimony, amphotericin B is the most effective option for the treatment of VL. Lipid formulations of amphotericin B are able to circumvent the toxic effect of conventional amphotericin B, and the total dose of these formulations can be administered over a short duration. However, cost is a major constraint in the use of lipid formulations of amphotericin B. Amphotericin B colloidal dispersion (ABCD), which is a less expensive lipid formulation, has not been tested for the treatment of VL in India. METHODS: In an open-label, randomized clinical trial, we evaluated the efficacy and safety of a 6-day course of ABCD administered to 3 different dose groups (total dose: 7.5 mg/kg [group A], 10 mg/kg [group B], and 15 mg/kg [group C]), each of which included a cohort of 135 patients. RESULTS: Although infusion-related fever and chills occurred in 56%-68% of patients in the 3 different dose groups, 401 of 405 patients completed the treatment. All 135 patients in group A completed treatment, and the final cure rate for this group was 97%. In the group that received the highest dose of ABCD (group C), severe backache, an unusual side effect, was observed in 8 patients (5.92%). Serious adverse effects led to the withdrawal of 2 patients (1.48%) each from group B and group C. CONCLUSIONS: Although the cost of ABCD is prohibitive, the high level of efficacy associated with short-term treatment with low-dose ABCD provides another alternative for the treatment of VL, especially in regions where VL is antimony refractory.
Authors: Caspar J Hodiamont; Piet A Kager; Aldert Bart; Henry J C de Vries; Pieter P A M van Thiel; Tjalling Leenstra; Peter J de Vries; Michèle van Vugt; Martin P Grobusch; Tom van Gool Journal: PLoS Negl Trop Dis Date: 2014-05-01