A Randomized Trial of a New Triple Drug Treatment for Lymphatic Filariasis

BACKGROUND: The recommended drug regimen for elimination of lymphatic filariasis outside sub-Saharan Africa is single dose of diethylcarbamazine (DEC) plus albendazole (ALB). Multiple annual treatments are required for elimination since this regimen does not sustainably reduce blood microfilaria (Mf) counts below the threshold required to interrupt transmission. This study tested the efficacy of a single dose of ivermectin (IVM) combined with DEC/ALB. METHODS: We conducted an open label, randomized clinical trial in which Wuchereria bancrofti-infected adults in Papua New Guinea were assigned to treatment with DEC/ALB once (n=61), DEC/ALB twice (n=61, baseline, 12 months) and IVM/DEC/ALB once (n=60). The primary outcome was complete clearance of blood Mf at 24 months. RESULTS: At 24 months 96% of participants treated with IVM/DEC/ALB were amicrofilaremic compared to 56% after single dose DEC/ALB (relative risk for Mf+ = 0.08 [0.02-0.34, 95% CI], p<0.001) and 75% after two annual doses of DEC/ALB (relative risk for Mf+ = 0.15 [0.03-0.62, 95% CI], p=0.009). Filarial antigen levels decreased markedly and to a similar degree after treatment with all 3 regimens. Moderate adverse events were more common after the triple than the two-drug regimen (27% vs. 5%, p<0.001). There were no serious adverse events. CONCLUSIONS: Treatment with a single dose of IVM/DEC/ALB was superior to a single dose or two annual doses of DEC/ALB for clearing Mf. There were no significant safety concerns. Widespread use of IVM/DEC/ALB could greatly accelerate elimination of lymphatic filariasis. (ClinicalTrials.gov, NCT01978771)