Indirect evidence from network meta-analyses of randomized controlled trials (RCTs) suggest that a pulse and taper (P-T) of vancomycin may be non-inferior to 10-days of fidaxomicin for the prevention of recurrent Clostridioides difficile infections (rCDI). The aim of this trial is:
1\) For first episodes and first recurrences of CDI, to test whether a vancomycin P-T is non-inferior to 10-days of fidaxomicin for the prevention of rCDI at 56 days
Inpatient or outpatient adults (≥18 years old) treated at the participating institutions.
First episode or first recurrence of CDI (i.e., second episode within 120 days) defined by a positive C. difficile assay (including PCR toxin gene detection, toxin enzyme immunoassay, and/or cell cytotoxicity neutralization assay) and the presence of either ≥3 unformed stools in <24 hours with a duration >24 hours, endoscopic/histologic evidence of pseudomembranous colitis, or ileus. For eligibility, CDI will be considered a first recurrence if the patient experiences 2 episodes within a 120-day timeframe; those with a first ever episode, or 2 episodes separated by more than 120 days, will be categorized as a first-episode.
Treatment with CDI-active antibiotics that will be continued throughout the trial (i.e., rifaximin for hepatic encephalopathy).
Planned or current treatment of the present episode of CDI with FMT, intravenous immunoglobulins, or other microbiome therapies (i.e., VOWST or REBYOTA).
Inability to take medications orally.
Ileostomy, colostomy, or total colectomy with ileorectal anastomosis.
Parallel
Fidaxomicin
DrugFidaxomicin 200mg PO BID x 10 days
Vancomycin capsule
DrugVancomycin 125mg PO QID x2 weeks, then 125mg PO BID x2 weeks, then 125mg PO daily x2 weeks
CDI Recurrence
Recurrence will be assessed by clinical record review (chart, laboratory, pharmacy records) and any direct patient interview. CDI recurrence will be defined by 1) three or more unformed stools in a 24-hour period, 2) a positive PCR for toxin gene or and/or detection of toxin by enzyme immunoassay or cell cytotoxicity neutralization assay, and 3) administration of CDI treatment. To avoid missing severe recurrences for cases of ileus, toxic megacolon, or pseudomembranous colitis on colonoscopy the test result and administration of treatment will fulfill criteria for a recurrence in the absence of three or more unformed stools.
All-Cause Mortality
All-cause mortality
All-Cause Mortality
All-cause mortality
Discontinuation of study drug due to adverse events
Discontinuation of the study drug due to any patient-reported adverse event
ER Visit or Hospital (Re)Admission
All-cause ER visits and hospital (re)admission
Quality of life: EuroQol 5 Dimensions 5 Levels (EQ-5D-5L)
patient quality of life will be assessed by the EQ-5D-5L scale Canadian calue set on enrolment and at day 56; higher scores indicate better health status
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