A Comparison of Fidaxomicin and Vancomycin in Patients With CDI Receiving Antibiotics for Concurrent Infections
Condition: Clostridium Difficile Infection (CDI)
MeSH terms: Infections; Communicable Diseases; Clostridium Infections
Intervention: Fidaxomicin; Vancomycin
Intervention description: Eligible patients randomized to receive open-label Fidaxomicin will receive 200 mg twice daily for 10 days or until the end of the duration of concomitant antibiotics exposure, whichever is longer.; Eligible patients randomized to Vancomycin will receive 125 mg orally four times daily for 10 days or until the end of the duration of concomitant antibiotics exposure, whichever is longer.
Intervention MeSH terms: Vancomycin; Fidaxomicin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 144.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: vancomycin; fidaxomicin; CDI; diarrhea

Summary:

      Administration of concomitant antibiotics (CA) is a known risk factor for treatment failure
      in the treatment of CDI, as well as for recurrence of CDI. Recent data suggested that among
      patients receiving CA, fidaxomicin is superior to vancomycin. While these data are
      encouraging, many clinicians remain unclear on how to apply these data to patient care.
      Additionally, patients were excluded from the trials presented to the FDA if it was expected
      that they would require ≥ 7 days of CA. Therefore, the clinical question still remains of how
      to apply these data to the real world patient who requires a long course of CA and develops
      CDI while on therapy. We therefore propose an open label, comparative and prospective study
      of fidaxomicin 200 mg twice daily vs oral vancomycin 125 mg four times daily for the
      treatment of CDI among patients who are receiving a long course of CA.

      We hypothesize that fidaxomicin will be superior to vancomycin with respect to clinical cure
      for patients with CDI.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients 18 years of age or older with >3 unformed stools/24 hours with positive stool
             test for C. difficile.

          -  Patients receiving ≥ 1 high or medium risk antibiotic for treatment of an infection
             other than CDI, for an anticipated duration of ≥ 5 days from the time of enrollment.

               -  High risk: carbapenems, 2nd-4th generation cephalosporins, fluoroquinolones,
                  clindamycin, and beta-lactam/beta-lactamase inhibitor combinations

               -  Medium risk: 1st generation cephalosporin, macrolides*, and aztreonam

                    -  *The macrolide would be considered to be low risk if patients are receiving
                       intermittent macrolides for prophylaxis only and not for treatment of an
                       acute infection

        Exclusion Criteria:

          -  Patients with severe-complicated disease that would compromise oral therapy
             (hypotenstion or shock, ileus or bowel obstruction, megacolon).

          -  Patients with an allergy to oral vancomycin or fidaxomicin.

          -  Patients anticipated to receive metronidazole after enrollment.

          -  Patients who already received oral vancomycin or metronidazole (either oral or
             intravenous) for > 24 hours within the preceding 72 hours at the time of enrollment.

          -  Patients anticipated to receive adjunctive C. difficile therapy (rifaxamin,
             nitazoxanide, tigecycline) after enrollment.

          -  Patients who are on laxatives before they are enrolled into the study, such as
             lactulose, if:

               -  Patients have had a recent dose adjustment;

               -  Baseline number of bowel movement while on laxatives is unknown.

               -  Number of bowel movements and/or consistency has not changed from baseline.

          -  Patients who have had colostomy or ileostomy

          -  Patients who will have colostomy or ileostomy after enrollment and before study ends

          -  Patients who are or will be on long-term (>12 weeks) medium or high-risk antibiotics
             prophylaxis after enrollment