Comparison of 6-Week Doxycycline vs 6-Week Rifampicin or 3 Weeks of Doxycycline Plus Rifampicin in the Treatment of Onchocerciasis: A Randomized, Placebo-Controlled, Double-Blind, Phase 2 Trial.

BACKGROUND: Depletion of has proven to be a validated curative treatment for filariasis. This trial investigated alternatives to the current treatment regimen for onchocerciasis: 6 weeks of doxycycline (DOX) at 200 mg daily.

METHODS: This randomized, placebo-controlled, double-blind, phase 2a trial with 5 treatment regimens was conducted in Ghana to determine (1) whether treatment times could be shortened as compared with 6 weeks of DOX at 200 mg daily by using a combination of DOX and rifampicin (RIF) for 3 weeks or (2) whether a dosage reduction to 6 weeks of DOX at 100 mg or a change to 6 weeks of RIF at 10 mg/kg daily would result in noninferior efficacy.

RESULTS: The primary outcome-the absence of onchocercomata with worms showing normal embryogenesis at 20 months-revealed that DOX at 200 mg or 100 mg for 6 weeks was superior to all other interventions. DOX + RIF for 3 weeks was less effective but superior to RIF alone and to placebo, suggesting that shorter regimens can be designed by combining antiwolbachials. Finally, depletion of in nodules 6 months after study onset strongly correlated with antiparasitic effects at 20 months.

CONCLUSIONS: Reduction of DOX from 200 to 100 mg daily facilitates implementation of this regimen, by aligning it to other regimens using 100 mg daily with a larger safety profile. The results also indicate that a combination of antiwolbachials might deliver effective regimens with shorter treatment times. Finally, the ability to predict 20-month end points of the slow-acting antiwolbachials by using depletion at 6 months will accelerate follow-up end points earlier than macrofilaricidal end points.

© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

PMID: 42813101