Single Dose Azithromycin in the Treatment of Adult Cholera
Status:
Completed
Trial end date:
2004-05-01
Target enrollment:
Participant gender:
Summary
Cholera remains an important cause of diarrhoeal illness and death in Asia, Africa and Latin
America. Antimicrobial therapy is an important adjunct to fluid therapy in the management of
patients with cholera, and should be given to all patients with clinically moderate-to-severe
disease since they can reduce the diarrhoea duration and stool volume by half. Current
therapy for cholera is limited by increasing prevalence of multiply-resistant strains of
Vibrio cholerae O1 or O139. Tetracycline and doxycycline had been the drugs of choice for
treating cholera, but multiply-resistant strains are now present in all areas where cholera
is endemic or epidemic. There is thus a need to identify alternative drugs that are effect in
treating this disease.
Azithromycin, a newer macrolide agent, is active in-vitro against V. cholerae, attains high
concentrations in the gut lumen, has a long half-life, and is better tolerated than
erythromycin, and older macrolide. In this study we will compare efficacy of a single, 1.0 g
oral doses of azithromycin and ciprofloxacin in male patients, aged 18-60 years, with cholera
due to V. cholerae O1 or O139. Patients with typical "Rice watery" stools of cholera, signs
of severe dehydration and characteristic cholera vibrios in a dark-field stool microscopy.
Patients who have coexisting illness which may confound assessment of the efficacy or safety
will not be eligible. Only those patients who have V. cholerae O1 or O139 isolated from their
pre-therapy stool and/or rectal swab culture and remains in the hospital for the entire
duration of the study will be eligible for efficacy evaluation. A written informed consent
will be obtained from each patients for their enrollment in the study.
Patients will be hospitalized for full 5 days, and asked to return for a follow up evaluation
7 days after discharge. After initial rehydration, patients will be observed for 4 hours, and
only those with ³ 20 ml/kg of watery stools during this period will be enrolled for study.
Treatment will be random, and blinded to study staff and patients. Clinical success of
therapy will be defined as resolution of watery stool within 48 hours of administration of
the study drug, and bacteriologic success will be defined as the inability to isolate V.
cholerae O1 or O139 from fecal/rectal swab cultures of patients after 48 hours of therapy,
i.e. on day 3 and on all subsequent days of the study. Patients in whom therapy clinically
fails will be treated for 3 days with an effective alternate drug without opening the study
code. Ninety one evaluable patients will be required in each group to show with a power of
80% and a type I error of 5% that the two treatment regimens are equivalent (i.e. the 95%
confidence interval for the difference in efficacy between the two groups is not greater than
10%).
If single-dose azithromycin therapy is found effective it will provide an important option
for the treatment V. cholerae infections, especially those caused by multiply-resistant
strains.
Phase:
Phase 3
Details
Lead Sponsor:
International Centre for Diarrhoeal Disease Research, Bangladesh