Clinical Trial: A Clinical Trial to Evaluate the Safety and Efficacy of Ciprofloxacin in the Treatment of Plague in Humans
Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional
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 Human
Brief Summary:
Plague is a severe, life-threatening disease. Plague occurs in focal locations worldwide, but over 95% of human cases reported to WHO are by countries in Africa. The most common clinical manifestations of human infection are bubonic, septicemic, and pneumonic plague. Untreated pneumonic or septicemic plague is fatal in over 90% of cases; untreated bubonic plague is fatal in over 50% of cases. Delayed and ineffectual treatment is a main contributor to elevated case fatality rates, which can be as high as 40%, and to the development of pneumonic plague and plague outbreaks.
Streptomycin is considered the treatment of choice, and prompt administration can reduce mortality to 5% or less. However, streptomycin may cause irreversible hearing loss and vestibular damage, reversible renal damage, and it is contraindicated during pregnancy. Tetracyclines, including doxycycline, are considered effective alternatives but they are bacteriostatic and relatively contraindicated for use in children aged < 8 years and pregnant women.
Ciprofloxacin is a relatively newer antimicrobial that is used extensively in clinical practice because of its broad-spectrum antimicrobial activity, excellent tissue and intracellular penetration, suitability for oral administration, and good overall tolerability. In vitro and animal studies suggest equivalent or greater activity of ciprofloxacin against Yersinia pestis when compared with streptomycin or tetracyclines. However, the efficacy of ciprofloxacin for the treatment of human plague has never been demonstrated, nor is it FDA approved for this indication.
Since 2004, CDC has collaborated with the Uganda Ministry of Health (MoH) and the Uganda Virus Research Institute (UVRI) to enhance surveillance, diagnosis, and ecological control of plague in Arua
Detailed Summary:
Plague is a life-threatening disease that requires immediate treatment with effective antimicrobials. Drugs with demonstrated efficacy include streptomycin, doxycycline, and to a lesser extent, gentamicin. Animal and in vitro studies suggest that fluoroquinolones, including ciprofloxacin, may be effective agents for treatment of plague. However, with the exception of a single case report, there are no published instances in which fluoroquinolones have been used successfully to treat plague in humans. There is a critical need to evaluate newer antimicrobials that have been shown to be efficacious in vitro and in animal studies, used extensively in the treatment of other illnesses in humans, work by a separate mechanism than antimicrobials currently used for treatment, and are widely available and affordable.
The objective of this study is to conduct a randomized, open-labeled, non-inferiority study comparing the safety and efficacy of ciprofloxacin to doxycycline, the national treatment standard in Uganda. This study is designed to test the following hypothesis: the safety and efficacy of ciprofloxacin for the treatment of plague in humans is not inferior to doxycycline. This study will result in a better understanding of the safety and efficacy of ciprofloxacin for the treatment of plague in humans. Information from this study will be used to expand the experience and knowledge base for the treatment of plague in humans and guide national and international treatment guidelines. Information from this study also will possibly add to the antiquated list of effective antimicrobials used to treat plague and possibly lead to a reduction in the overall morbidity and mortality caused by plague and its treatment.
The randomized clinical trial provides the best design to distinguish treatment effects from other effects such as bias
Sponsor: Centers for Disease Control and Prevention
Current Primary Outcome: all cause mortality [ Time Frame: 14 days ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- time to defervesence [ Time Frame: days to weeks ]
- antimicrobial associated adverse events [ Time Frame: days to weeks ]
Original Secondary Outcome: Same as current
Information By: Centers for Disease Control and Prevention
Dates:
Date Received: November 17, 2010
Date Started: December 2010
Date Completion:
Last Updated: September 10, 2012
Last Verified: September 2012
