A Clinical Trial to Evaluate the Safety and Efficacy of Ciprofloxacin in the Treatment of Plague in Humans
Status:
Unknown status
Trial end date:
1969-12-31
Target enrollment:
Participant gender:
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 and Nebbi Districts. Through these efforts, we have collected data on over
2,400 cases of clinically diagnosed plague occurring from 1999 through 2009. In 2008, UVRI
and CDC staff investigated 163 suspect plague cases: 57 (35%) had laboratory-confirmed plague
illness, of which 14 patients (25%) died.
Because plague is a relatively rare disease that mainly affects people living in rural,
impoverished areas, it receives limited attention for research and development of affordable
and sustainable diagnostic and treatment options. However, because plague cannot be
eradicated, and because it causes high case fatality and has the potential for widespread
person to person transmission, continued research should not be neglected.
The objective of this clinical trial 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 for plague, in patients aged > 8 years. The primary
outcome for this trial will be patient outcome 14 days from enrollment and initiation of
treatment. Patient outcome will be evaluated only for those patients with
laboratory-confirmed plague illness.
Information gathered from this proposed study will help optimize management of naturally
occurring plague in humans in many countries of the world, including Uganda and the United
States, by providing clinicians with more choices for optimal antimicrobial treatment. This
is particularly true in resource limited rural regions such as Uganda where intravenous or
intramuscular injections are less available. Ciprofloxacin currently is being used in Uganda
and other plague endemic areas of the world for treatment of other infectious conditions,
including infectious diarrhea and lower respiratory infections. In Uganda, ciprofloxacin is
widely available in health facilities and local drug shops, and is affordable.
Phase:
Phase 2
Details
Lead Sponsor:
Centers for Disease Control and Prevention
Collaborators:
Ministry of Health, Uganda MRC/UVRI and LSHTM Uganda Research Unit MRC/UVRI Uganda Research Unit on Aids