Multicentric, controlled clinical study to evaluate effectiveness and safety of miltefosine and allopurinol for canine leishmaniosis.

The aim of this trial was to evaluate the effectiveness and safety of miltefosine-allopurinol combination therapy vs. the current reference combination therapy, meglumine antimoniate-allopurinol, for canine leishmaniosis. Dogs included in the study exhibited clinical signs of the disease, were positive by PCR and serologically positive by immunofluorescent antibody test for leishmaniosis, and negative for ehrlichiosis. Dogs were divided into two groups: Group 1 was treated with 2 mg/kg of miltefosine orally once daily for 28 days and 10 mg/kg of allopurinol orally twice daily for 7 months; Group 2 was treated with 50 mg/kg of meglumine antimoniate sub-cutaneously twice daily for 28 days and allopurinol (same dose as Group 1) for 7 months. Dogs were examined according to the following schedule: pre-inclusion, Day 0 (D0), D14, D28, D84, D140 and D196. At each visit, blood, urine and bone marrow samples were collected. Parameters monitored included haematology, biochemistry, protein electrophoresis, serology, urinary protein/creatinine ratio and RTQ-PCR performed on bone marrow aspirates. A significant reduction in total clinical score and parasite load was observed in both groups over the 7-month study period (P < 0.0001), with no significant difference between groups (P = 0.3). The safety of miltefosine-allopurinol combination therapy was confirmed by lack of effect on renal and hepatic parameters and adverse reactions. Miltefosine, in combination with allopurinol, offers a safe, convenient and effective alternative treatment option for canine leishmaniosis compared to the reference therapy.