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NCT01243437

PHASE2

A Clinical Trial to Evaluate the Safety and Efficacy of Ciprofloxacin in the Treatment of Plague in Humans

Sponsor: Centers for Disease Control and Prevention

View on ClinicalTrials.gov

Summary

This study is a randomized, open-label, non-inferiority clinical trial evaluating the safety and efficacy of oral ciprofloxacin compared to oral doxycycline for the treatment of plague in humans. Participants aged 8 years and older with suspected plague presenting to health facilities in Uganda will be enrolled and randomized to receive either ciprofloxacin or doxycycline. Plague is a severe, potentially fatal infectious disease caused by Yersinia pestis, with high case fatality rates if not promptly treated. Current treatment options include aminoglycosides and tetracyclines such as doxycycline; however, limitations include availability, route of administration, and safety concerns in certain populations. Ciprofloxacin is a widely available fluoroquinolone with favorable pharmacokinetics and demonstrated activity against Y. pestis in vitro and in animal models, but clinical data in humans are limited. The primary outcome is all-cause mortality within 14 days of enrollment among participants with laboratory-confirmed plague. Secondary outcomes include time to defervescence and antimicrobial-associated adverse events. This study aims to determine whether ciprofloxacin is non-inferior to doxycycline and to inform treatment guidelines for plague, particularly in resource-limited settings.

Official title: A Randomized, Non-inferiority, Active Controlled Clinical Trial to Evaluate the Safety and Efficacy of Ciprofloxacin Versus Doxycycline in the Treatment of Plague in Humans

Key Details

Gender

All

Age Range

8 Years - Any

Study Type

INTERVENTIONAL

Enrollment

Start Date

2010-12

Completion Date

2013-06

Last Updated

2026-06-03

Healthy Volunteers

Conditions

Plague

Interventions

DRUG

ciprofloxacin

* For adults and children aged \> 15 years: 500 mg orally every 12 hours for 10 days or until the patient has been fever-free for 24 hours, whichever is longer; * For children aged 8-15 years: 15 mg/kg (maximum 500 mg per dose) orally every 12 hours for 10 days or until the patient has been fever-free for 24 hours, whichever is longer.

DRUG

doxyxcycline

* For adults and children weighing 45 kg or more: 200 mg orally one time as an initial loading dose, followed by 100 mg orally every 12 hours for 10 days or until the patient has been fever-free for 24 hours, whichever is longer; * For children weighing less than 45 kg: 4.4 mg/kg orally one time as an initial loading dose, followed by 2.2 mg/kg orally every 12 hours for 10 days or until the patient has been fever-free for 24 hours, whichever is longer.

Inclusion Criteria: * Suspect cases of plague will be eligible and will be asked to give consent for study enrollment using the following criteria: 1. any person, including women and persons who are minorities, who; 2. must be aged 8 years or older, and; 3. must have had potential exposure to rodents and/or fleas or contact with a confirmed plague case, and; 4. must have a fever of at least 38ºC that developed rapidly, and have at least one of the following: * One or more buboes, defined as a tender lymph node swelling \> 1cm in diameter, or; * Clinical suspicion of pneumonic plague (e.g. prostration, cough, increased respiratory rate, hemoptysis and/or purulent sputum), or * Clinical suspicion of cutaneous plague (lesion) * Clinical suspicion of plague and epidemiologic link with other cases Exclusion Criteria: * Patients with suspected plague illness will be considered ineligible for the study and will be excluded from study enrollment using the following criteria: * Any women who is pregnant, or; * Any woman who is breast-feeding, or; * Any person aged \< 8 years of age, or; * Any patient with: * signs of plague meningitis * hypotension unresponsive to fluid therapy * an illness severity score of \> 16 at time of enrollment (see below) * known allergy to ciprofloxacin or doxycycline * taken tetracyclines, quinolones, gentamicin, streptomycin, trimethoprim-sulfamethoxazole, or chloramphenicol in the 24 hours preceding study enrollment Patients who are pregnant, breast-feeding, or aged \< 8 years will be excluded because doxycycline has a relative contraindication for use in these populations due to drug deposition in calcifying areas of bones and teeth, enamel hypoplasia, and decreased linear skeletal growth rate. \[22, 23\] Please see section 10.2 for additional background describing the reasoning to exclude patients from these populations. Please see section 3.5 for the specifics regarding the timing of urine pregnancy testing. The illness severity score is a composite measure adapted from the APACHE-II and Glasgow Coma scores that estimates the severity of a patient's illness at enrollment. Because most clinic locations are remote with little or no laboratory capacity, the illness severity score utilizes only non-biochemical parameters. Patients will not be tested for Human Immunodeficiency Virus (HIV), and known or suspected HIV-positive patients will not be excluded. Because this study will be conducted in a remote region of Uganda where no prisons are located, the enrollment of prisoners is not applicable to our study. If for some unforeseen reason a prisoner presents to a study clinic location for treatment of suspected plague, the prisoner will be excluded from the trial. All study resources will be available and treatment following the UMOH national plague treatment guidelines will be offered to patients with suspected plague at the UMOH collaborating clinics who are not eligible for enrollment or who declined to consent.

Locations (1)

Uganda Ministry of Health: selected Arua and Nebbi district health centres

Arua, Uganda