Comparison of six weeks doxycycline versus six weeks rifampicin or three weeks of the combination of doxycycline plus rifampicin in the treatment of onchocerciasis: a randomized, placebo-controlled, double-blind, phase 2 trial

Abstract

Abstract 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 doxycycline (DOX) at 200mg daily. Methods This randomized, placebo-controlled, double-blind, Phase 2a trial with 5 different treatment regimens was conducted in Ghana to determine whether treatment times could be shortened compared to 6 weeks DOX 200mg daily by using a combination of DOX and rifampicin (RIF) for 3 weeks, or whether a dosage reduction to 6 weeks DOX 100mg or a change to 6 weeks RIF at 10 mg/kg daily would result in non-inferior efficacy. Results The primary outcome “Absence of onchocercomata with worms showing normal embryogenesis at 20 months“showed that DOX 200mg or 100mg for 6 weeks were superior to all other interventions. Combination of 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 anti-Wolbachials. Finally, depletion of Wolbachia in nodules 6 months after study onset strongly correlated with anti-parasitic effects at 20 months. Conclusions Reduction of DOX from 200 to 100mg daily facilitates implementation of this regimen, as it aligns it to other regimens using 100mg daily with a larger safety profile. The results also indicate that combination of anti-Wolbachials might deliver effective regimens with shorter treatment time. Finally, the ability to predict 20-month endpoints of the slow-acting anti-Wolbachials by using Wolbachia depletion at 6 months will accelerate follow-up endpoints earlier than macrofilaricidal endpoints.