DiarrheaPhase 4NCT00359970
Azithromycin, With or Without Loperamide, to Treat Travelers' Diarrhea
A Phase 4 study testing Azithromycin 500 mg, Azithromycin 1000 mg and Loperamide in people with Diarrhea, run by The University of Texas Health Science Center, Houston at 1 site in Mexico.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diarrhea
- What is being tested?
- Azithromycin 500 mg, Azithromycin 1000 mg and Loperamide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 176 participants
- Where
- 1 siteMexico
- Study dates
- Jun 2002to Aug 2003
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 less than or equal to 72 hours.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Mexico1 site
University of Texas Enteric Disease Research Clinics
Guadalajara, Jalisco
About this study
Official title: Loperamide Plus Azithromycin More Effectively Treats Travelers' Diarrhea In Mexico Than Azithromycin Alone
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.
Read more
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.
Read the 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.
- Conditions
- Diarrhea
- Being tested
- Azithromycin 500 mg, Azithromycin 1000 mg, Loperamide, Placebo
- Keywords
- Diarrhea, Travel, Travelers' diarrhea, Azithromycin, Loperamide, Treatment, Antibiotic
- Medical subject headings
- Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azithromycin 500 mgDrug
Also called Zithromax, Zmax
A single 500 mg dose at the start of treatment
Azithromycin 1000 mgDrug
Also called Zithromax, Zmax
A single 1000 mg dose at the start of treatment
LoperamideDrug
Also called IModium, Loperamide HCl
A single 4 mg loading dose at the start of treatment and then 2 mg after each loose stool
PlaceboOther
A single loading dose at the start of treatment and then a dose after each loose stool
| Study group | Role | What they receive |
|---|---|---|
| Azithromycin 500 mg plus Placebo | Active comparator | a single 500 mg dose of Azitrhomycin at the start of treatment; a single loading dose of placebo at the start of treatment and then a dose of placebo after each loose stool Receives: Drug: Azithromycin 500 mg; Other: Placebo |
| Azithromycin 1000 mg plus Placebo | Active comparator | a single 1000 mg dose of Azitrhomycin at the start of treatment; a single loading dose of placebo at the start of treatment and then a dose of placebo after each loose stool Receives: Drug: Azithromycin 1000 mg; Other: Placebo |
| Azithromycin 500 mg plus Loperamide | Experimental | a single 500 mg dose of Azitrhomycin at the start of treatment; a single 4 mg loading dose of Loperamide at the start of treatment and then 2 mg Loperamide after each loose stool Receives: Drug: Azithromycin 500 mg; Drug: Loperamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hours from beginning treatment to passage of last unformed stool
Measured: subjects recorded the time and form of all stools passed during a 4 day observation period
Secondary outcomes (5)
Number of unformed stools passed per 24 hour period
Measured: 24 hours after treatment
Number of subjects with symptoms of enteric disease per 24 hour period
Symptoms of enteric disease include nausea, vomiting, abdominal cramps, gas, urgency, and tenesmus.
Measured: 24 hours after treatment
Number of treatment failures
Treatment failure is defined as persisting ill after 72 hours
Measured: 72 hours after treatment
Percent of subjects in whom enteropathogen isolated from an enrollment stool sample was eradicated from a day 5 stool
Measured: 5 days after treatment
Percent of subjects continuing to pass 3 or more (enrollment criteria) unformed stools in a 24 hour period
Measured: 24 hours after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2006 (estimated)
- Study startJun 2002
- Primary completionAug 2003
- Study completionAug 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DiarrheaStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 176 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Charles D Ericsson, The University of Texas Health Science Center, Houston
- Investigators
- Charles D. Ericsson, MD, Principal investigator, University of Texas Medical School at Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00359970
- Sponsor's protocol ID
- HSC-MS-02-082
- Status last verified
- Jun 2015
- First submitted
- 1 Aug 2006
- Last updated
- 19 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1086/378746. Epub 2003 Sep 30.
PubMed 14557959Ericsson CD, DuPont HL, Okhuysen PC, Jiang ZD, DuPont MW. Loperamide plus azithromycin more effectively treats travelers' diarrhea in Mexico than azithromycin alone. J Travel Med. 2007 Sep-Oct;14(5):312-9. doi: 10.1111/j.1708-8305.2007.00144.x.
PubMed 17883462
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Loperamide Plus Azithromycin More Effectively Treats Travelers' Diarrhea In Mexico Than Azithromycin Alone
- ClinicalTrials.gov ID
- NCT00359970
- Acronym / sponsor ID
- HSC-MS-02-082
- Conditions
- Diarrhea
- Keywords
- Diarrhea, Travel, Travelers' diarrhea, Azithromycin, Loperamide, Treatment, Antibiotic
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 176 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- Jun 2002
- Primary completion
- Aug 2003 (actual)
- Study completion
- Aug 2003 (actual)
- First posted
- 3 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Azithromycin 500 mg plus Placebo | Active comparator | Drug: Azithromycin 500 mg, Other: Placeboa single 500 mg dose of Azitrhomycin at the start of treatment; a single loading dose of placebo at the start of treatment and then a dose of placebo after each loose stool |
| Azithromycin 1000 mg plus Placebo | Active comparator | Drug: Azithromycin 1000 mg, Other: Placeboa single 1000 mg dose of Azitrhomycin at the start of treatment; a single loading dose of placebo at the start of treatment and then a dose of placebo after each loose stool |
| Azithromycin 500 mg plus Loperamide | Experimental | Drug: Azithromycin 500 mg, Drug: Loperamidea single 500 mg dose of Azitrhomycin at the start of treatment; a single 4 mg loading dose of Loperamide at the start of treatment and then 2 mg Loperamide after each loose stool |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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 less than or equal to 72 hours.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azithromycin 500 mgAlso: Zithromax, ZmaxA single 500 mg dose at the start of treatment | Drug | Azithromycin 500 mg plus Loperamide, Azithromycin 500 mg plus Placebo |
| Azithromycin 1000 mgAlso: Zithromax, ZmaxA single 1000 mg dose at the start of treatment | Drug | Azithromycin 1000 mg plus Placebo |
| LoperamideAlso: IModium, Loperamide HClA single 4 mg loading dose at the start of treatment and then 2 mg after each loose stool | Drug | Azithromycin 500 mg plus Loperamide |
| PlaceboA single loading dose at the start of treatment and then a dose after each loose stool | Other | Azithromycin 1000 mg plus Placebo, Azithromycin 500 mg plus Placebo |
Primary outcome
Hours from beginning treatment to passage of last unformed stool
Time frame: subjects recorded the time and form of all stools passed during a 4 day observation period
5 secondary outcomes
Number of unformed stools passed per 24 hour period
Time frame: 24 hours after treatment
Number of subjects with symptoms of enteric disease per 24 hour period
Time frame: 24 hours after treatment
Number of treatment failures
Time frame: 72 hours after treatment
Percent of subjects in whom enteropathogen isolated from an enrollment stool sample was eradicated from a day 5 stool
Time frame: 5 days after treatment
Percent of subjects continuing to pass 3 or more (enrollment criteria) unformed stools in a 24 hour period
Time frame: 24 hours after treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2015.
- Background: PubMed 14557959Adachi 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. doi: 10.1086/378746. Epub 2003 Sep 30.
- Background: PubMed 17883462Ericsson CD, DuPont HL, Okhuysen PC, Jiang ZD, DuPont MW. Loperamide plus azithromycin more effectively treats travelers' diarrhea in Mexico than azithromycin alone. J Travel Med. 2007 Sep-Oct;14(5):312-9. doi: 10.1111/j.1708-8305.2007.00144.x.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles D. Ericsson, MD principal investigator
University of Texas Medical School at Houston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Azithromycin 500 mg, Azithromycin 1000 mg and Loperamide in people with Diarrhea, run by The University of Texas Health Science Center, Houston at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hours from beginning treatment to passage of last unformed stool (time frame: subjects recorded the time and form of all stools passed during a 4 day observation period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00359970, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2015.