A Comparison of Fidaxomicin and Vancomycin in Patients With CDI Receiving Antibiotics for Concurrent Infections

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Clostridium Difficile Infection (CDI)

Intervention / Treatment
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* Drug: Fidaxomicin
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fidaxomicin<br>Fidaxomicin 200 mg PO BID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer. | Drug: Fidaxomicin<br>* 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.<br>* Other names: Dificid, Dificlir, OPT-80, PAR-101;|
| Active Comparator: Vancomycin<br>Vancomycin 125 mg PO QID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer. | Drug: Vancomycin<br>* 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.<br>* Other names: Vancocin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Cure: Resolution of Diarrhea | Resolution of diarrhea defined as ≤ 3 unformed stools for 2 consecutive days maintained until the end of therapy and for 2 days afterwards. The treatment course was at least 10 days, but it could be extended to a maximum of 12 weeks. | length of treatment plus 2 days, from a minimum of 12 to a maximum of 86 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of CDI | Recurrence is defined as all three of the following within 4 weeks after successfully completing study treatment: reappearance of symptoms of CDI (>3 unformed stools in a 24 hour period; a positive stool PCR test for C. difficile; and the need for retreatment with an agent active against C. difficile). | 30 days after treatment's end (maximum of 114 days) | 
| 30-day Mortality | Death in subjects who completed the study treatment and died within 30 days after end of treatment | 40 to 114 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CDI, vancomycin, fidaxomicin, diarrhea