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Phase 3 non-inferiority evidence

Single-dose oral zoliflodacin was non-inferior to ceftriaxone plus azithromycin for urogenital gonorrhoea

A phase 3 open-label trial at 17 clinics in five countries including Thailand randomized people aged 12+ with suspected uncomplicated urogenital gonorrhoea 2:1 to single oral zoliflodacin 3 g (621) or IM ceftriaxone 500 mg plus oral azithromycin 1 g (309). Day 6±2 microbiological cure in microbiological ITT was 90.9% (460/506) versus 96.2% (229/238). The comparator-minus-zoliflodacin difference was 5.3%, with upper 95% CI 8.6%, below the 12% margin. Events were mostly mild/moderate and no serious events occurred.

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Key findings

  • N=930; cure 90.9% vs 96.2%; difference 5.3%, 95% CI 1.4-8.6 below 12% margin; similar safety; no serious events; single oral dose avoids injection.
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Why this matters globally

A new-mechanism oral drug expands options and stewardship as ceftriaxone resistance threatens, but deployment needs susceptibility surveillance to preserve effectiveness.

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Thai researcher contribution

Rossaphorn Kittiyaowamarn and Nittaya Phanuphak of Thailand's Ministry of Public Health and HIV-NAT participated in the five-country clinical network.

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Limitations to consider

Open label despite masked labs; a 12% margin permits some lower cure. Participants were 88% male and the primary endpoint urogenital, limiting pharyngeal, rectal, female and adolescent conclusions. Short follow-up cannot establish population resistance evolution.

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Verify the original sources

The LancetRead the original article

DOI: 10.1016/s0140-6736(25)01953-1

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