Traveler's Diarrhea
Conditions
Brief summary
The purpose of this study is to prove the non-inferiority of Rifamycin SV-MMX® versus Ciprofloxacin for the treatment of adults with traveller's diarrhoea.
Interventions
DRUGRifamycin SV-MMX®
2 Rifamycin SV-MMX® 200 mg tablets and 1 placebo to ciprofloxacin capsule, b.i.d.
DRUGCiprofloxacin
1 ciprofloxacin 500 mg capsule and 2 placebos to Rifamycin SV-MMX® 200 mg tablets, b.i.d.
Sponsors
Dr. Falk Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent, * Men or women between 18 and 85 years of age, * History of arriving from their country of residence in the industrialized part of the world within the past 4 weeks, * Presenting with acute infectious diarrhoea (defined as at least 3 unformed, watery or soft stools accompanied by symptoms within 24 hours preceding randomisation with duration of illness ≤ 72 hours), * Presence of one or more signs or symptoms of enteric infection (moderate to severe gas/flatulence, nausea, vomiting, abdominal cramps or pain, rectal tenesmus, fecal urgency), * Women of childbearing potential had to apply during the entire duration of the study a highly effective method of birth control
Exclusion criteria
* Residency in any country with high incidence rate of TD within the past 6 months, * Fever (defined as a body (oral) temperature \>100.4°F or 38.0°C; antipyretic medication should not have been administered in the 6 hours prior to this assessment), * Known or suspected infection with non-bacterial pathogen, * Presence of diarrhoea of \>72 hours duration, * Presence of grossly bloody stool, * Presence of moderate or severe dehydration (i.e. symptoms of hypovolemia such as orthostatic hypotension, dizziness or wrinkling of skin), * History of inflammatory bowel disease or celiac disease,
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Last Unformed Stool (TLUS) | 5 days | Time to Last Unformed Stool (TLUS), defined as the interval in hours between the first dose of study drug and the last unformed stool passed, after which clinical cure was declared. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Clinical Cure | 5 days | Clinical Cure Rate: 24-hour period with no clinical symptoms except mild flatulence, no fever, no watery stools and no more than 2 soft stools OR 48-hour period with no stools or only formed stools, and no fever, with our without symptoms of enteric infection. |
Countries
Ecuador, Guatemala, India
Participant flow
Recruitment details
Recruited from November 2010 until January 2016
Pre-assignment details
A total of 835 patients were enrolled and were randomised to one of the 2 treatment groups according to the randomisation plan. All randomised patients received at least one dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Group A Rifamycin SV-MMX® 200 mg tablets
Rifamycin SV-MMX®: 2 Rifamycin SV-MMX® 200 mg tablets and 1 placebo to ciprofloxacin capsule, b.i.d. | 420 |
| Group B Ciprofloxacin 500 mg capsules
Ciprofloxacin: 1 ciprofloxacin 500 mg capsule and 2 placebos to Rifamycin SV-MMX® 200 mg tablets, b.i.d. | 415 |
| Total | 835 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 16.1 | 40.4 years STANDARD_DEVIATION 16.6 | 40.2 years STANDARD_DEVIATION 16.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 75 Participants | 68 Participants | 143 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 342 Participants | 344 Participants | 686 Participants |
| Region of Enrollment Ecuador | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Guatemala | 14 participants | 15 participants | 29 participants |
| Region of Enrollment India | 405 participants | 400 participants | 805 participants |
| Sex: Female, Male Female | 215 Participants | 197 Participants | 412 Participants |
| Sex: Female, Male Male | 205 Participants | 218 Participants | 423 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 420 | 0 / 415 |
| other Total, other adverse events | 36 / 420 | 32 / 415 |
| serious Total, serious adverse events | 0 / 420 | 0 / 415 |
Outcome results
Primary
Time to Last Unformed Stool (TLUS)
Time to Last Unformed Stool (TLUS), defined as the interval in hours between the first dose of study drug and the last unformed stool passed, after which clinical cure was declared.
Time frame: 5 days
Population: Efficacy results were reported for Full Analysis Set, which all randomised patients (as randomised) who received at least one dose of study medication. Patients with uncertainty as to whether they had received study medication or not (e.g., due to lost to follow-up) were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Time to Last Unformed Stool (TLUS) | 44.3 hours |
| Group B | Time to Last Unformed Stool (TLUS) | 40.3 hours |
Secondary
Number of Patients With Clinical Cure
Clinical Cure Rate: 24-hour period with no clinical symptoms except mild flatulence, no fever, no watery stools and no more than 2 soft stools OR 48-hour period with no stools or only formed stools, and no fever, with our without symptoms of enteric infection.
Time frame: 5 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Number of Patients With Clinical Cure | 357 Participants |
| Group B | Number of Patients With Clinical Cure | 352 Participants |