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 Wolbachia 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 Wolbachia 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 Wolbachia depletion at 6 months will accelerate follow-up end points earlier than macrofilaricidal end points.