Clinical trial
An Open-label, Randomised, Non-inferiority Trial of the Efficacy and Safety of Ciprofloxacin Versus an Aminoglycoside Followed by Ciprofloxacin in the Treatment of Bubonic Plague
Name
45-18
Description
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.
Trial arms
Trial start
2020-02-15
Estimated PCD
2024-04-30
Trial end
2025-03-31
Status
Recruiting
Phase
Early phase I
Treatment
Ciprofloxacin
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.
Arms:
Ciprofloxacin Arm, Control arm
Streptomycin
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.
Arms:
Control arm
Gentamicin
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.
Arms:
Control arm
Size
463
Primary endpoint
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:
11 days
Eligibility criteria
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
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'An open label, randomised, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in treatment of 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.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 463, 'type': 'ESTIMATED'}}
Updated at
2024-06-17
1 organization
3 products
3 indications
Organization
University of OxfordProduct
CiprofloxacinIndication
PlagueIndication
BubonicIndication
PneumonicProduct
StreptomycinProduct
Gentamicin