Azithromycin, With or Without Loperamide, to Treat Travelers' Diarrhea - Full Text View

Sponsored by:	The University of Texas Health Science Center, Houston
Information provided by:	The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier:	NCT00359970

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 IV

MedlinePlus related topics: Antibiotics Diarrhea

Drug Information available for: Azithromycin Loperamide Loperamide hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Bio-equivalence Study
Official Title:	Loperamide Plus Azithromycin More Effectively Treats Travelers’ Diarrhea In Mexico Than Azithromycin Alone

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00359970

Locations

Mexico, Jalisco
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:

Adachi JA, Ericsson CD, Jiang ZD, DuPont MW, Martinez-Sandoval F, Knirsch C, DuPont HL. Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis. 2003 Nov 1;37(9):1165-71. Epub 2003 Sep 30.

Study ID Numbers:	HSC-MS-02-082
Study First Received:	August 1, 2006
Last Updated:	August 1, 2006
ClinicalTrials.gov Identifier:	NCT00359970
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

Study placed in the following topic categories:

Signs and Symptoms
Digestive System Diseases
Diarrhea
Signs and Symptoms, Digestive
Gastrointestinal Diseases

Dysentery
Azithromycin
Loperamide
Intestinal Diseases
Gastroenteritis

Additional relevant MeSH terms:

Anti-Infective Agents
Anti-Bacterial Agents
Therapeutic Uses

Gastrointestinal Agents
Pharmacologic Actions
Antidiarrheals

ClinicalTrials.gov processed this record on January 16, 2009