Azithromycin, With or Without Loperamide, to Treat Travelers' Diarrhea

This study has been completed.
Sponsor:
Information provided by:
The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:
NCT00359970
First received: August 1, 2006
Last updated: NA
Last verified: August 2006
History: No changes posted
  Purpose

In a previous study azithromycin proved as efficacious as levofloxacin in the treatment of travelers' diarrhea in Mexico. Because the addition of loperamide to some antibiotics (e.g., trimethoprim-sulfamethoxazole and ofloxacin) has proven more efficacious than antibiotic alone in the treatment of travelers' diarrhea, we decided to study the addition of loperamide to azithromycin.

US adults with acute diarrhea in Guadalajara Mexico were randomized to receive azithromycin in two different doses or loperamide plus azithromycin.

The duration of diarrhea was shorter (11 hours) in the combination-treated group compared to the antibiotic-treated groups (34 hours). The percentage of subjects continuing to pass 6 or more unformed stools in the first 24 hours was less (1.7%) in the combination-treated group than in the antibiotic-treated groups (20%).

We feel loperamide should routinely be added to an antibiotic to optimize treatment of travelers' diarrhea.


Condition Intervention Phase
Diarrhea
Drug: Azithromycin 1000 mg or 500 mg
Drug: Loperamide 4 mg loading then 2 mg after each loose stool
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Loperamide Plus Azithromycin More Effectively Treats Travelers’ Diarrhea In Mexico Than Azithromycin Alone

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center, Houston:

Primary Outcome Measures:
  • Hours from beginning treatment to passage of last unformed stool

Secondary Outcome Measures:
  • Number of unformed stools passed per 24 h period.
  • Number of subjects with no, mild, moderate or severe symptoms of enteric disease per 24 h period.
  • Number of treatment failures.
  • Number of subjects in whom an enteric bacterial pathogen isolated from an enrollment stool sample was eradicated from a day 5 stool.
  • Percent of subjects continuing to pass 3 or more (enrollment criteria), or 6 or more (moderate to severe disease), unformed stools in a 24 h period.

Estimated Enrollment: 180
Study Start Date: June 2002
Estimated Study Completion Date: August 2003
Detailed Description:

Background. The combination of loperamide and trimethoprim-sulfamethoxazole or a fluoroquinolone has proven to be more efficacious than the antimicrobial agent alone in the treatment of travelers’ diarrhea. We set out to prove loperamide plus azithromycin was more efficacious that azithromycin alone.

Methods. During the summers of 2002-3, 176 US adults recently arrived in Guadalajara, Mexico were enrolled in a prospective, double-blinded, randomized trial of the treatment of acute diarrhea. Subjects received single doses (1000 mg or 500 mg) of azithromycin or a single 500 mg dose of azithromycin plus loperamide. Subjects gave a pre and post treatment stool sample for analysis and maintained daily diaries of symptoms and passage of stools.

Results. The MIC90 of azithromycin for all E. coli and Shigella was 0.03 and 4 µg/ml with eradication rates in day 5 stools of 88% and 100%, respectively. The duration of diarrhea was significantly (p=0.0002) shorter following treatment with azithromycin plus loperamide (11 h) than with either dose of azithromycin alone (34 h). In the first 24 h the average number of unformed stools passed was 3.4 (azithromycin-alone) and 1.2 (combination) for a significant (p<0.0001) difference of 2.2 unformed stools. This difference equated with 20% of azithromycin-treated subjects continuing to pass 6 or more unformed stools in the first 24 h post treatment compared with only 1.7% of combination-treated subjects.

Conclusions. For the treatment of travelers’ diarrhea in an E. coli predominant region of the world a single 500 mg dose of azithromycin appeared as effective as a 1000 mg dose. Loperamide plus 500 mg azithromycin was safe and more effective than either dose of azithromycin. To realize the substantial clinical benefit that accrues to a subset of subjects, we feel loperamide should routinely be used in combination with an antimicrobial agent to treat travelers’ diarrhea.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligible subjects included men or women, recently arrived in Mexico, at least 18 years of age, who developed acute diarrhea, which was defined as passage of 3 or more unformed stools in the preceding 24 hours accompanied by one or more signs or symptoms of enteric infection (e.g., nausea, vomiting, abdominal cramps, tenesmus, passage of grossly bloody stools or fecal urgency) with a duration of illness of  72 hours.

Exclusion Criteria:

  • Exclusion criteria included pregnancy, breast feeding, an unstable medical condition, taking two or more doses of an antidiarrheal medication in the 24 hours before enrollment or any number of doses of symptomatic therapy within 2 hours of enrollment, or receiving an antimicrobial drug with expected activity against enteric bacterial pathogens within 7 days prior to enrollment.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00359970

Locations
Mexico
University of Texas Enteric Disease Research Clinics
Guadalajara, Jalisco, Mexico
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Principal Investigator: Charles D. Ericsson, MD University of Texas Medical School at Houston
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00359970     History of Changes
Other Study ID Numbers: HSC-MS-02-082
Study First Received: August 1, 2006
Last Updated: August 1, 2006
Health Authority: United States: Food and Drug Administration

Keywords provided by The University of Texas Health Science Center, Houston:
Diarrhea
Travel
Travelers' diarrhea
Azithromycin
Loperamide
Treatment
Antibiotic

Additional relevant MeSH terms:
Diarrhea
Dysentery
Digestive System Diseases
Gastroenteritis
Gastrointestinal Diseases
Intestinal Diseases
Signs and Symptoms
Signs and Symptoms, Digestive
Antidiarrheals
Loperamide
Gastrointestinal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014