Abstract
BackgroundAlternative treatments for visceral leishmaniasis (VL) are required in East Africa. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India.MethodsA multi-centre randomized-controlled trial (RCT) to compare efficacy and safety of PM (20 mg/kg/day for 21 days) and PM plus sodium stibogluconate (SSG) combination (PM, 15 mg/kg/day and SSG, 20 mg/kg/day for 17 days) with SSG (20 mg/kg/day for 30 days) for treatment of VL in East Africa. Patients aged 4–60 years with parasitologically confirmed VL were enrolled, excluding patients with contraindications. Primary and secondary efficacy outcomes were parasite clearance at 6-months follow-up and end of treatment, respectively. Safety was assessed mainly using adverse event (AE) data.FindingsThe PM versus SSG comparison enrolled 205 patients per arm with primary efficacy data available for 198 and 200 patients respectively. The SSG & PM versus SSG comparison enrolled 381 and 386 patients per arm respectively, with primary efficacy data available for 359 patients per arm. In Intention-to-Treat complete-case analyses, the efficacy of PM was significantly lower than SSG (84.3% versus 94.1%, difference = 9.7%, 95% confidence interval, CI: 3.6 to 15.7%, p = 0.002). The efficacy of SSG & PM was comparable to SSG (91.4% versus 93.9%, difference = 2.5%, 95% CI: −1.3 to 6.3%, p = 0.198). End of treatment efficacy results were very similar. There were no apparent differences in the safety profile of the three treatment regimens.ConclusionThe 17 day SSG & PM combination treatment had a good safety profile and was similar in efficacy to the standard 30 day SSG treatment, suggesting suitability for VL treatment in East Africa.Clinical Trials Registration www.clinicaltrials.gov NCT00255567
Highlights
The parasitic disease visceral leishmaniasis (VL) has an incidence of 500,000 new cases annually occurring primarily in India, Bangladesh, Nepal, Sudan, and Brazil and is fatal if untreated [1]
The efficacy of paromomycin sulphate (PM) monotherapy for the treatment of VL has been demonstrated in India, where it is registered for the treatment of VL [9] and the safety and efficacy of the combination of sodium stibogluconate (SSG) and Paromomycin sulphate (PM) has been demonstrated in trials in India and a small Kenyan study [10,11]
Kg/day plus PM at 15 mg/kg/day for 17 days); aPatients 4–17 years old were classified as children and patients 18–60 years old were classified as adults. bThese are presented as mean (SD). cClassification based on World Health Organization child growth standards in patients #19 years or using body mass index in those $20 years. d340 out of 386, 203 out of 205, and 335 out of 381 patients were tested for HIV in the SSG, PM and SSG & PM arms respectively
Summary
The parasitic disease visceral leishmaniasis (VL) has an incidence of 500,000 new cases annually occurring primarily in India, Bangladesh, Nepal, Sudan, and Brazil and is fatal if untreated [1]. It is an important disease in several other East African countries, with an incidence rate of 30,000 cases per year and a mortality rate of 4,000 deaths per year [2,3]. SSG unresponsiveness is emerging in East Africa and treatment with a combination of SSG & PM may limit the spread of the emerging resistant strains of leishmania parasites [8]. Paromomycin sulphate (PM) has been shown to be efficacious for VL treatment in India
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