Efficacy and Safety of AmBisome® in combination with sodium stibogluconate or miltefosine and miltefosine monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

Visceral leishmaniasis, or kala-azar, is a parasitic disease which is fatal without treatment. A 17-day treatment of sodium stibogluconate (SSG) with paromomycin (PM) is the recommended treatment in eastern Africa, but requires painful injections, causes adverse events, and patients need to stay in the hospital during treatment. An affordable, safe and effective oral treatment would be preferable. Whilst research to identify entirely new drugs is underway, existing treatments are being optimized as a short-term solution. Combination regimens based on AmBisome and miltefosine have been shown to be safe and effective in treating Indian patients, but there are no published data from use of these drugs in combination regimens from Africa, where efficacy of treatments can be different from India. Three regimens were evaluated for treating VL in eastern Africa, using AmBisome in combination with SSG or miltefosine, or miltefosine alone. Once again, drugs which are effective in India were found to be less so in African patients, and none of the regimes tested showed sufficiently high definitive cure rates to evaluate in Phase III trials. The results also suggest miltefosine was under-dosed in children and so allometric dosing, which takes into account the differences in drug metabolism seen in children compared to adults, needs to be studied.