Low-dose azithromycin did not meet the noninferiority margin compared with standard-dose azithromycin in achieving clinical and serological cure in polymerase chain reaction-confirmed active yaws, according to research published in Lancet Global Health.
Between June 2015 and July 2016, 583 children aged 6 to 15 years were enrolled in a noninferiority, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02344628) to determine the efficacy of low-dose (20 mg/kg) vs standard-dose (30 mg/kg) azithromycin for the treatment of active and latent yaws. Participants were randomly assigned 1:1 to either low-dose (n=292) or standard-dose (n=291) groups, and follow-up was conducted at 4 weeks and 6 months.
The primary outcome was cure at 6 months, defined as lesion healing at 4 weeks for those with active yaws (polymerase chain reaction-positive lesions for of Treponema pallidum ssp pertenue) and at least a 4-fold decrease in rapid plasma reagin titer from baseline to 6 months for active and latent yaws cases. A noninferiority margin of 10% was used.
Follow-up at 6 months was completed for 157 of 191 patients with active yaws, and cure was achieved in 61 (80.3%) of 76 low-dose and 68 (84.0%) of 81 of standard-dose patients. The difference in cure was 3.7% (95% CI, −8.4% to 15.7%), which did not meet the noninferiority criteria. Results were similar in participants with presumed latent yaws, as serological cure responses did not differ between the treatment groups and no serious adverse events were reported for either treatment group.
Low-dose azithromycin appears to be an effective treatment, but a small primary study population of patients with active yaws coupled with lower than expected serological cure response in both groups highlight the need for further research “before low-dose azithromycin can be unequivocally adopted as the standard of care,” concluded the researchers.
Marks M, Mitjà O, Bottomley C, et al. Comparative efficacy of low-dose vs standard-dose azithromycin for patients with yaws: a randomised non-inferiority trial in Ghana and Papua New Guinea [published online February 15, 2018]. Lancet Glob Health. doi: 10.1016/S2214-109X(18)30023-8