Ciprofloxacin Versus an Aminoglycoside Followed by Ciprofloxacin for Bubonic Plague

Phase

Condition

N/A

Treatment

Gentamicin

Ciprofloxacin

Streptomycin

Clinical Study ID

NCT04110340

45-18

All Genders

Study Summary

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:

to evaluate the level and kinetics of anti-Y. pestis antibodies of patients (bubonic and pneumonic plague) included in the study (anti-F1 ELISA techniques) at D1, D11, D21, M3 for patients who are positive at D21, and M12 for patients who are positive at M3.

The tertiary objectives are:

to evaluate the level and kinetics of the levels of anti-Y. pestis antibodies and circulating F1 antigen of the patients (bubonic and pneumonic plague) included in the study (Luminex MagPix techniques with a Multiplex containing anti-F1 and rLcrV antigens and an F1 antigen capture multiplex) at D1, D11, D21, M3 for patients positive at D21, and M12 for patients who are positive at M3.

Observational non-comparative study of pneumonic plague

The primary objective is to document the efficacy and safety of the currently recommended combination therapy treatment of pneumonic plague - an aminoglycoside (streptomycin or gentamicin) and ciprofloxacin combination therapy.
The secondary and tertiary objectives of the bubonic plague trial also apply to the pneumonic plague cohort.

Eligibility Criteria

Inclusion

Inclusion Criteria for randomisation to the bubonic plague treatment trial:

Bubonic plague

Patients of any age AND
Recent onset (< 10 days) of fever (uncorrected axillary temperature ≥ 37.5C) or history of fever AND
One or more buboes (tender lymph node swelling) AND
Residence or travel to a plague endemic area in Madagascar within 14 days of the onset of symptoms AND
Patients identified as clinically suspected of plague by health personnel (doctors or paramedics)

Exclusion Criteria to the bubonic plague treatment trial:

Known allergy to aminoglycosides or fluoroquinolones
Tendinitis
Myasthenia gravis
Theophylline or warfarin use
Already treated for bubonic or pneumonic plague in the preceeding 3 months
Women who report being pregnant

Inclusion of patients to the pneumonic plague observational cohort:

• Suspected, probable and confirmed cases of pneumonic plague

Study Design

Gentamicin

February 15, 2020

February 05, 2025

Study Description

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.

Connect with a study center

Professor Mamy Randria
Antananarivo,
Madagascar
Site Not Available

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