Rifaximin, Loperamide and the Combination to Treat Travelers' Diarrhea

Primary Outcome Measures:

• The major outcome parameter was time from initiation of therapy until passage of the last unformed stool before becoming well (TLUS).
  

Secondary Outcome Measures:

• Secondary Outcome Variables:
  
• 1. Time to passage of last unformed stool - standard definition of TLUS for antibiotics (18, 20) where wellness is declared at any time during 5 days regardless of later recurrence of continuing illness during the observation period;
  
• 2. Number of unformed stools passed during two days of therapy;
  
• 3. Number of unformed stools passed during the five days of study;
  
• 4. Improvement in diarrhea (<half the number of daily entry unformed stools in 24 hours) by 24 hours and 48 hours;
  
• 5. Treatment failure defined as: a. failure to achieve wellness during five days of study (achieve a TLUS-5 d); b. Deterioration during treatment and removed from further clinical evaluation, or, c. Occurrence of a relapse after achieving wellness during
  
• 6. Occurrence of relapse during five day surveillance (occurrence of diarrhea after having a TLUS);
  
• 7. TLUS in 48 hours - last unformed stool passed during the 48 hours that loperamide is being given (rapid symptomatic improvement);
  
• 8. Number of days of moderate or severe enteric symptoms;
  
• 9. Number of days passing any number of unformed stools plus any degree (mild, moderate or severe) of daily enteric symptoms (must have both present each day);
  
• 10. Subjects global assessment of efficacy by day of study;
  
• 11. Number of hours where schedule of activities were altered because of illness;
  
• 12. Number of hours confined to bed because of diarrhea;
  
• 13. Dropped from study due to adverse reaction;
  
• 14. Number of doses of loperamide (or loperamide placebos) taken;
  
• 15. Microbiologic eradication/failure.
  

During short-term study, adult U.S. students in Mexico (n = 310) with acute diarrhea (≥ 3 unformed stools with enteric symptoms) were enrolled in a double-blind, randomized trial wherein they were given rifaximin 200 mg three times a day for 3 days (R) (n = 102), loperamide 4 mg initially followed by 2 mg after each unformed stool not to exceed 8 mg/day for 2 days (L) (n = 104) or both drugs in the same dosage schedule (L/R) (n = 104). The major outcome parameter was time from initiation of therapy until passage of the last unformed stool before becoming well (TLUS).