Current treatment regimens for bubonic plague vary and a number of recommendations for licensed and unlicensed treatments have been made in clinical management guidelines.


In Madagascar, the first-line treatment is a sequential administration of an aminoglycoside followed by the fluoroquinolone ciprofloxacin.  An alternative treatment is ciprofloxacin alone. These regimens however are supported by limited clinical evidence and the few drugs that have received regulatory approval were licensed primarily on the basis of animal data.

The IMASOY trial aims to generate clinical evidence for two regimens that are currently used in Madagascar, where over 80% of global cases are detected.  The trial closed to recruitment in March 2024 having enrolled over 220 patients with confirmed or probable bubonic plague. Patients were randomised to receive either: a 3-day course of injectable aminoglycoside (originally streptomycin which was replaced by gentamicin when streptomycin became unavailable) – followed by 7-day ciprofloxacin OR a 10-day ciprofloxacin-only course.

The ciprofloxacin-only regimen is compared to the reference treatment on non-inferiority basis, with a non-inferiority margin (delta) 15%, assuming 90% therapeutic response in the control group, 2.5% one-sided alpha, 90% power, 10% losses to follow-up, and 1:1 randomisation. The primary endpoint of the trial is the proportion of patients with bubonic plague who have a favourable therapeutic response to treatment.


To complement the clinical data generated in the trial and prepare for the potential uptake of a new first-line treatment regimen in clinical practice, the trial also incorporated a qualitative sub-study to investigate the acceptability of a ciprofloxacin monotherapy among clinicians in Madagascar.

Full details of the trial design can be found in the protocol.

The results of the trial are expected to be available towards the end of 2024.

The trial was conducted as a collaboration between ISARIC (University of Oxford), Institut Pasteur de Madagascar, Centre Infectiologie Charles Mérieux and the London School of Hygiene and Tropical Medicine. Funding was provided by Wellcome and the UK Foreign Commonwealth and Development Office. Contact Josephine Bourner for more information.