Comparison of Repeated Doses of Ivermectin Versus Ivermectin Plus Albendazole for the Treatment of Onchocerciasis: A Randomized, Open-label, Clinical Trial.

ABSTRACT

BACKGROUND: Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone. METHODS: This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment and at 6, 18, and 36 months. The primary outcome was the proportion of fertile and viable female worms in onchocercomata excised at 36 months. RESULTS: Posttreatment nodule histology showed that 15/135 (11.1%), 22/155 (14.2%), 35/154 (22.7%), and 20/125 (16.0%) living female worms had normal embryogenesis in the IVM annual, IVM semiannual, IVM+ALB annual, and IVM+ALB semiannual groups, respectively (P = .1229). Proportions of dead worms also did not differ between the 4 groups (P = .9198). Proportions of patients without MF at 36 months (1 year after the last treatment) were 35/56 (63%) after annual IVM, 42/59 (71%) after semiannual IVM, 39/64 (61%) after annual IVM+ALB, and 43/53 (81%) after semiannual IVM+ALB. CONCLUSIONS: The combination treatment of IVM plus ALB was no better than IVM alone for sterilizing, killing adult worms, or achieving sustained MF clearance. However, semiannual treatment was superior to annual treatment for achieving sustained clearance of Onchocerca volvulus MF from the skin (P = .024). CLINICAL TRIALS REGISTRATION ISRCTN50035143.