Clinical trial NCT02692651: A Comparison of Fidaxomicin and Vancomycin in Patients With CDI Receiving Antibiotics for Concurrent Infections
Official title: A Comparison of Fidaxomicin and Oral Vancomycin for the Treatment of Clostridium Difficile Infection (CDI) in Hospitalized Patients Receiving Concomitant Antibiotics for the Treatment of Concurrent Systemic Infections
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Clostridium Difficile Infection (CDI)
Keywords: vancomycin
fidaxomicin
CDI
diarrhea
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-02-26
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Clinical Cure: Resolution of Diarrhea
timeFrame: length of treatment plus 2 days, from a minimum of 12 to a maximum of 86 days
Secondary outcomes:
measure: Recurrence of CDI
timeFrame: 30 days after treatment's end (maximum of 114 days)
measure: 30-day Mortality
timeFrame: 40 to 114 days
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Ypsilanti
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
Study officials:
affiliation: University of Michigan
name: A. Krishna Rao, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: