Single Dose Azithromycin in the Treatment of Adult Cholera

NCT00229944 | Completed Phase 3

• 1 other identifier: 98-022
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cholera

Keywords

Azithromycin; V. cholerae O1 / O139; adults; Bangladesh; Clinical trial

Outcome Measures

Primary Outcomes (2)

• Clinical success

• Bacteriological Success

Secondary Outcomes (7)

• Rates of clinical and bacteriologic relapse.

• Duration of diarrhoea in hours, and duration of fecal excretion of V. cholerae O1 or O139 in days.

• Volume of watery/liquid stool for each 6 and 24 hour of the study, and also the total amount of watery/liquid stools during the study period.

• Frequency of vomiting and the amount of vomitus, and proportion of patients with vomiting on each study day.

• Intake of oral and intravenous fluids for each 24 hour as well as the entire duration of the study.

Interventions

Azithromycin DRUG

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18 - 60 years
• Gender: Male (To facilitate accurate measurement of stool and urine, and also due to the difficulties in hospitalizing women for longer duration)
• Duration of illness: 24 hours or less
• Written informed consent for participation in the study
• Dehydration status: Signs of severe dehydration as determined by World Health Organization criteria.
• Positive stool dark-field microscopic examination for V. cholerae, and subsequent isolation of V. cholerae O1 or O139 from an admission culture of a stool or rectal swab sample.

You may not qualify if:

• History of receiving even one dose of an antimicrobial agent effective in the treatment of cholera, and even a single fose of the drugs under evaluation.
• Concomitant infection requiring antimicrobial therapy other than the study drugs which may interfere with evaluation of either the efficacy or safety of the study drugs.
• A concomitant illness which may confound evaluation of outcome or is a contraindication for use of either of the study drugs (chronic heart, lung, of kidney disease, or instance), or conditions which may confound evaluation of adverse events of the study drugs.

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Pfizer: collaborator
• Tufts Medical Center: collaborator

Study Sites (1)

Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh

Dhaka, 1212, Bangladesh

Location

Related Publications (1)

• Saha D, Karim MM, Khan WA, Ahmed S, Salam MA, Bennish ML. Single-dose azithromycin for the treatment of cholera in adults. N Engl J Med. 2006 Jun 8;354(23):2452-62. doi: 10.1056/NEJMoa054493.

  PMID: 16760445 RESULT

MeSH Terms

Conditions

Cholera

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Debasish Saha, MBBS,MS

  International Centre for Diarrhoeal Disease Research, Bangladesh

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 29, 2005
• First Posted: September 30, 2005
• Study Start: December 1, 2002
• Study Completion: May 1, 2004
• Last Updated: July 21, 2006

Record last verified: 2005-09

Locations

BA (1)