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

NCT02692651 | Completed Phase 4 Results FDA Drug

• 1 other identifier: Merck Fidaxo
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 2

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.

Conditions

Clostridium Difficile Infection (CDI)

Keywords

vancomycin; fidaxomicin; CDI; diarrhea

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Recurrence of CDI

  30 days after treatment's end (maximum of 114 days)

• 30-day Mortality

  40 to 114 days

Study Arms (2)

Fidaxomicin

ACTIVE COMPARATOR

Fidaxomicin 200 mg PO BID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer.

Drug: Fidaxomicin

Vancomycin

ACTIVE COMPARATOR

Vancomycin 125 mg PO QID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer.

Drug: Vancomycin

Interventions

Fidaxomicin DRUG

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.

Also known as: Dificid, Dificlir, OPT-80, PAR-101

Fidaxomicin

Vancomycin DRUG

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.

Also known as: Vancocin

Vancomycin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

St. Joseph Mercy Hospital

Ypsilanti, Michigan, 48197, United States

Location

Related Publications (1)

• Rao K, Zhao Q, Bell J, Krishnan J, Henig O, Daniel J, Sawaya K, Albin O, Mills JP, Petty LA, Gregg K, Kaul D, Malani AN, Pogue J, Kaye KS. An Open-Label, Randomized Trial Comparing Fidaxomicin With Oral Vancomycin for the Treatment of Clostridioides difficile Infection in Hospitalized Patients Receiving Concomitant Antibiotics for Concurrent Infections. Clin Infect Dis. 2024 Feb 17;78(2):277-282. doi: 10.1093/cid/ciad606.

  PMID: 37797310 DERIVED

MeSH Terms

Conditions

Clostridium Infections; Diarrhea

Interventions

Fidaxomicin; OPT 80; Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Polyketides; Macrocyclic Compounds; Polycyclic Compounds; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Krishna Rao
• Organization: University of Michigan

krirao@med.umich.edu

734 615-9730

Study Officials

• A. Krishna Rao, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Internal Medicine

Study Record Dates

• First Submitted: February 23, 2016
• First Posted: February 26, 2016
• Study Start: May 1, 2017
• Primary Completion: May 23, 2021
• Study Completion: June 23, 2021
• Last Updated: March 25, 2022
• Results First Posted: March 25, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)