1. A phase II, non-comparative randomised trial of two treatments involving liposomal amphotericin B and miltefosine for post-kala-azar dermal leishmaniasis in India and Bangladesh.
- Author
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Sundar S, Pandey K, Mondal D, Madhukar M, Kamal Topno R, Kumar A, Kumar V, Kumar Verma D, Chakravarty J, Chaubey R, Kumari P, Rashid MU, Maruf S, Ghosh P, Raja S, Rode J, den Boer M, Das P, Alvar J, Rijal S, and Alves F
- Subjects
- Humans, Bangladesh, Male, Adult, Adolescent, Female, Middle Aged, Young Adult, Child, India, Treatment Outcome, Drug Therapy, Combination, Amphotericin B therapeutic use, Amphotericin B adverse effects, Amphotericin B administration & dosage, Phosphorylcholine analogs & derivatives, Phosphorylcholine therapeutic use, Phosphorylcholine administration & dosage, Phosphorylcholine adverse effects, Antiprotozoal Agents therapeutic use, Antiprotozoal Agents adverse effects, Antiprotozoal Agents administration & dosage, Leishmaniasis, Visceral drug therapy, Leishmaniasis, Cutaneous drug therapy, Leishmaniasis, Cutaneous parasitology
- Abstract
Background: In Southeast Asia, treatment is recommended for all patients with post-kala-azar dermal leishmaniasis (PKDL). Adherence to the first-line regimen, twelve weeks of miltefosine (MF), is low and ocular toxicity has been observed with this exposure period. We assessed the safety and efficacy of two shorter-course treatments: liposomal amphotericin B (LAmB) alone and combined with MF., Methodology/principal Findings: An open-label, phase II, randomized, parallel-arm, non-comparative trial was conducted in patients with parasitologically confirmed PKDL, 6 to ≤60 years. Patients were assigned to 20 mg/kg LAmB (total dose, in five injections over 15 days) alone or combined with allometric MF (3 weeks). The primary endpoint was definitive cure at 12 months, defined as complete resolution of papular and nodular lesions and >80% re-pigmentation of macular lesions. Definitive cure at 24 months was a secondary efficacy endpoint. 118/126 patients completed the trial. Definitive cure at 12 months was observed in 29% (18/63) patients receiving LAmB and 30% (19/63) receiving LAmB/MF (mITT), increasing to 58% and 66%, respectively, at 24 months. Most lesions had resolved/improved at 12 and 24 months for patients receiving LAmB (90%, 83%) and LAmB/MF (85%, 88%) by qualitative assessment. One death, unrelated to study drugs, was reported; no study drug-related serious adverse events were observed. The most frequent adverse drug reactions were MF-related vomiting and nausea, and LAmB-related hypokalaemia and infusion reactions. Most adverse events were mild; no ocular adverse events occurred., Conclusions/significance: Both regimens are suitably safe and efficacious alternatives to long-course MF for PKDL in South Asia., Trial Registration: CTRI/2017/04/008421., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: MdB declares consultancy fees from DNDi. The remaining authors report no conflicts of interest., (Copyright: © 2024 Sundar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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