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ABSTRACT: Background
SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa.Methods
A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments.Results
In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92) in all arms. At D210, definitive cure was 87% (95% CI: 77-97) for AmBisome + SSG, 77% (95% CI 64-90) for AmBisome + miltefosine and 72% (95% CI 60-85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults.Conclusion
No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated.Trial registration
The study was registered with ClinicalTrials.gov, number NCT01067443.
SUBMITTER: Wasunna M
PROVIDER: S-EPMC5023160 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
Wasunna Monique M Njenga Simon S Balasegaram Manica M Alexander Neal N Omollo Raymond R Edwards Tansy T Dorlo Thomas P C TP Musa Brima B Ali Mohammed Hassan Sharaf MH Elamin Mohammed Yasein MY Kirigi George G Juma Rashid R Kip Anke E AE Schoone Gerard J GJ Hailu Asrat A Olobo Joseph J Ellis Sally S Kimutai Robert R Wells Susan S Khalil Eltahir Awad Gasim EA Strub Wourgaft Nathalie N Alves Fabiana F Musa Ahmed A
PLoS neglected tropical diseases 20160914 9
<h4>Background</h4>SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa.<h4>Methods</h4>A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safet ...[more]