Single Dose Azithromycin in the Treatment of Adult Cholera

This study has been completed.
Sponsor:
Collaborators:
Pfizer
Tufts Medical Center
Information provided by:
International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier:
NCT00229944
First received: September 29, 2005
Last updated: July 20, 2006
Last verified: September 2005
  Purpose

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.


Condition Intervention Phase
Cholera
Drug: Azithromycin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Controlled Clinical Trial to Compare Efficacy of a Single Dose of Azithromycin Versus a Single Dose of Ciprofloxacin in the Treatment of Adults With Clinically Severe Cholera Due to V. Cholerae O1 or O139

Resource links provided by NLM:


Further study details as provided by International Centre for Diarrhoeal Disease Research, Bangladesh:

Primary Outcome Measures:
  • Clinical success
  • Bacteriological Success

Secondary Outcome Measures:
  • 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.
  • Proportion of patients with resolution of diarrhoea on each study day.
  • Proportion of patients with a positive culture for infecting V. cholerae O1 or O139 on each study day.

Estimated Enrollment: 220
Study Start Date: December 2002
Estimated Study Completion Date: May 2004
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00229944

Locations
Bangladesh
Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh
Dhaka, Bangladesh, 1212
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Pfizer
Tufts Medical Center
Investigators
Study Director: Debasish Saha, MBBS,MS International Centre for Diarrhoeal Disease Research, Bangladesh
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00229944     History of Changes
Other Study ID Numbers: 98-022
Study First Received: September 29, 2005
Last Updated: July 20, 2006
Health Authority: Bangladesh: Ethical Review Committee

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Azithromycin
V. cholerae O1 / O139
adults
Bangladesh
Clinical trial

Additional relevant MeSH terms:
Cholera
Vibrio Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014