A Phase 3 interventional study of Ciprofloxacin and Streptomycin in Plague, Bubonic and Plague, Pneumonic, sponsored by University of Oxford. Completed at 1 site in Madagascar. Per ClinicalTrials.gov, last updated 2025-03-06.
Sponsored by University of Oxford · Phase 3, Interventional, and Treatment
The primary objective of this trial is to test the hypothesis that ciprofloxacin monotherapy given (orally, intravenously, or combination) for 10 days is non-inferior to an aminoglycoside (given on days 1-3) followed by ciprofloxacin (given on days 4-10) in the treatment of bubonic plague.
Secondary objectives are:
The tertiary objectives are:
Observational non-comparative study of pneumonic plague
An individually randomised, open label, non-inferiority trial of ciprofloxacin versus an aminoglycoside and ciprofloxacin in patients with bubonic plague. We are using a non-inferiority design since the overall cure rate for bubonic plague without septicaemia with streptomycin is approximately 95%. As a result, demonstrating superiority would be unnecessary and impractical given the sample size that would be required. Our aim is therefore to demonstrate that ciprofloxacin alone is not more than 15% inferior to an aminoglycoside followed by ciprofloxacin. (15% is the non-inferiority margin in our study). We will recruit patients with a clinical suspicion of bubonic plague, but the size of our sample is powered based on an intention to treat infected patients sample size of 190, where infected is defined as a confirmed or probable case of bubonic plague. As a result the total number of patients to be enrolled will be higher than 190. We estimate that we will need to recruit approximately 600 patients with bubonic plague to achieve a sample size of 190 confirmed/probable bubonic plague patients. However, to mitigate risks of being under-powered we will propose to recruit for three full seasons with a minimum target of 190 confirmed/probable cases. Should we achieve the target of 190 confirmed/probable bubonic plague cases before the end of the final transmission season, we will nevertheless continue to recruit until the end of the season to retain power in the event of different treatment success percentages and to allow us to increase precision.
We will also recruit and collect data on patients with pneumonic plague, who will be enrolled in to a parallel observational cohort.
University of Oxford is the lead sponsor of 812 studies on the registry; 119 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria for randomisation to the bubonic plague treatment trial:
Bubonic plague
Exclusion Criteria to the bubonic plague treatment trial:
Inclusion of patients to the pneumonic plague observational cohort:
Adults: Ciprofloxacin 500mg orally twice daily (or 400mg IV twice daily for those who cannot take oral medication) for 10 days; Children:Ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 10 days.
Drug: Ciprofloxacin
Adults: streptomycin 1g twice daily for three days, followed by ciprofloxacin 500mg orally twice daily (or ciprofloxacin 400mg twice daily by IV for those who cannot take it orally) for an additional 7 days. OR 2.5mg/kg IV gentamicin twice daily for 3 days followed by ciprofloxacin 500 mg orally twice daily (or ciprofloxacin 400 mg twice daily IV for those who cannot take oral) for a further 7 days. Children: streptomycin 15mg/kg twice daily for three days followed by ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 7 additional days. OR 2.5mg/kg IV gentamicin twice daily for 3 days, followed by ciprofloxacin 15mg/kg (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take the oral route) for a further 7 days.
Drug: Ciprofloxacin · Drug: Streptomycin · Drug: Gentamicin
Adults: Ciprofloxacin 500mg orally twice daily (or 400mg IV twice daily for those who cannot take oral medication) for 10 days; Children:Ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 10 days. Patients who begin intravenous therapy may switch to oral administration once they are able to swallow or once deemed clinically appropriate by the treating physician.
Adults: streptomycin 1g twice daily for three days, followed by ciprofloxacin 500mg orally twice daily (or ciprofloxacin 400mg twice daily by IV for those unable to take orally) for an additional 7 days. Children: streptomycin 15mg/kg twice daily for three days followed by ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 7 additional days. Patients who begin intravenous therapy may switch to oral administration once they are able to swallow or once deemed clinically appropriate by the treating physician.
Adults: 2.5mg/kg IV gentamicin twice daily for 3 days followed by ciprofloxacin 500 mg orally twice daily (or ciprofloxacin 400 mg twice daily IV for those who cannot take oral) for a further 7 days. Children: 2.5mg/kg IV gentamicin twice daily for 3 days, followed by ciprofloxacin 15mg/kg (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take the oral route) for a further 7 days.
Proportion of patients with bubonic plague with a therapeutic response (assessed on day 11).Therapeutic response is defined as follows for subjects with a visible bubo:
* Alive * Absence of fever * Has not received alternative treatment for plague * No clinical decision to continue anti-plague antibiotics beyond day 10
Time frame: 11 days
Bubonic plague
• Proportion of patients without fever (uncorrected axillary temperature \<37.5C) at Day 4
Time frame: 4 days
Bubonic plague
• Proportion of patients with a pain score \< 3 at Day 4 (using pain scale questionnaires)
Time frame: 4 days
Bubonic plague
• Proportion of patients with a pain score \< 3 at Day 11 (using pain scale questionnaires)
Time frame: 11 days
Bubonic plague
• Mean % change in bubo size at Day 4 (measured by use of calipers and/or ultrasound)
Time frame: 4 days
Bubonic plague
• Mean % change in bubo size at Day11 (measured by use of calipers and/or ultrasound)
Time frame: 11 days
Bubonic plague
• Proportion of patients experiencing a serious adverse event on or before Day 4
Time frame: 4 days
Bubonic plague
• Proportion of patients experiencing a serious adverse event on or before Day 11
Time frame: 11 days
Bubonic plague
• Proportion of patients experiencing a serious adverse event on or before Day 21
Time frame: 21 days
Bubonic plague
• Proportion of patients who are fully adherent to the study treatment schedule.
Time frame: 21 days
Pneumonic plague
Proportion of patients with a therapeutic response at Day 11. Therapeutic response is defined as follows: * Alive * Resolution of fever (uncorrected axillary temperature \<37.5C) * Resolution of tachypnoea (RR\< 24 in adults, but age-specific in children)
Time frame: 11 days
Pneumonic plague
• Proportion of patients without fever (uncorrected axillary temperature \<37.5C) at Day 4
Time frame: 4 days
Pneumonic plague
• Proportion of patients with tachypnoea resolution (RR\< 24 in adults, but age-specific in children) at Day 4
Time frame: 4 days
Pneumonic plague
• Proportion of patients experiencing a serious adverse event on or before Day 4
Time frame: 4 days
Pneumonic plague
• Proportion of patients experiencing a serious adverse event on or before Day 11
Time frame: 11 days
Pneumonic plague
• Proportion of patients experiencing a serious adverse event on or before Day 21
Time frame: 21 days
Pneumonic plague
• Proportion of patients who are fully adherent to the study treatment schedule.
Time frame: 21 days
Therapeutic response is defined as follows for subjects with a visible bubo:
* Alive AND * Absence of fever at D11 AND * At least a 25% decrease in bubo size (in the case of multiple buboes, the largest bubo) AND * Has not received alternative treatment for plague AND * No clinical decision to continue anti-plague antibiotics beyond day 10 ● Therapeutic response is defined as follows for subjects with small buboes that are palpable but not measurable: * Alive AND * Absence of fever at D11 AND * Bubo has not enlarged AND * Has not received alternative treatment for plague AND * No clinical decision to continue anti-plague antibiotics beyond day 10
Time frame: 11 days
Plan to share: Yes — Anonymised data relating to the published analyses will be made available through an existing online repository (either at the University of Oxford or LSHTM) once the trial results are published.
Time frame: Anticipated release date: May 2025
Access criteria: To be confirmed
This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Plague