Clostridium Difficile Infection (CDI)Phase 4NCT02692651
A Comparison of Fidaxomicin and Vancomycin in Patients With CDI Receiving Antibiotics for Concurrent Infections
A Phase 4 study testing Fidaxomicin and Vancomycin in people with Clostridium Difficile Infection (CDI), run by University of Michigan at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile Infection (CDI)
- What is being tested?
- Fidaxomicin and Vancomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 May 2017to 23 Jun 2021
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
Show all 12Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan
Ann Arbor, Michigan, 48109
St. Joseph Mercy Hospital
Ypsilanti, Michigan, 48197
About this study
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
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)
- Being tested
- Fidaxomicin, Vancomycin
- Keywords
- vancomycin, fidaxomicin, CDI, diarrhea
- Medical subject headings
- Clostridium Infections, Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FidaxomicinDrug
Also called Dificid, Dificlir, OPT-80, PAR-101
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.
VancomycinDrug
Also called Vancocin
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: length of treatment plus 2 days, from a minimum of 12 to a maximum of 86 days
Secondary outcomes (2)
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).
Measured: 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
Measured: 40 to 114 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2016 (estimated)
- Study start1 May 2017
- Primary completion23 May 2021
- Study completion23 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridium Difficile Infection (CDI)Studies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Krishna Rao, University of Michigan
- Investigators
- A. Krishna Rao, MD, MS, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02692651
- Sponsor's protocol ID
- Merck Fidaxo
- Status last verified
- Mar 2022
- First submitted
- 23 Feb 2016
- Last updated
- 25 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37797310
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02692651
- Acronym / sponsor ID
- Merck Fidaxo
- Conditions
- Clostridium Difficile Infection (CDI)
- Keywords
- vancomycin, fidaxomicin, CDI, diarrhea
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 May 2017 (actual)
- Primary completion
- 23 May 2021 (actual)
- Study completion
- 23 Jun 2021 (actual)
- First posted
- 26 Feb 2016 (estimated)
- Results
- Posted 25 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fidaxomicin | Active comparator | Drug: FidaxomicinFidaxomicin 200 mg PO BID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer. |
| Vancomycin | Active comparator | Drug: VancomycinVancomycin 125 mg PO QID for 10 days or until the end of the duration of concomitant antibiotic exposure, whichever is longer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FidaxomicinAlso: Dificid, Dificlir, OPT-80, PAR-101Eligible 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. | Drug | Fidaxomicin |
| VancomycinAlso: VancocinEligible 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. | Drug | Vancomycin |
Primary outcome
Clinical Cure: Resolution of Diarrhea
Time frame: length of treatment plus 2 days, from a minimum of 12 to a maximum of 86 days
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.
2 secondary outcomes
Recurrence of CDI
Time frame: 30 days after treatment's end (maximum of 114 days)
30-day Mortality
Time frame: 40 to 114 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37797310Rao 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
A. Krishna Rao, MD, MS principal investigator
University of Michigan
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fidaxomicin and Vancomycin in people with Clostridium Difficile Infection (CDI), run by University of Michigan at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Cure: Resolution of Diarrhea (time frame: length of treatment plus 2 days, from a minimum of 12 to a maximum of 86 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02692651, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2022.