Recurrent Clostridium Difficile InfectionPhase 2NCT03462459
Efficacy of Oral Vancomycin Prophylaxis for Prevention of Recurrent Clostridium Difficile Infection
A Phase 2 study testing Vancomycin in people with Recurrent Clostridium Difficile Infection and Clostridium Difficile Infection, run by University of Wisconsin, Madison at 2 sites in United States.
Trial summary
This study evaluates the efficacy of prophylaxis with oral vancomycin for preventing recurrent Clostridium difficile Infection (CDI) in patients who have experienced at least one CDI episode in the last 180 days and are receiving antibiotics for a non CDI condition. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Clostridium Difficile Infection, Clostridium Difficile Infection, CDI
- What is being tested?
- Vancomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 May 2018to 6 Jul 2023
- Phase
- Phase 2
- 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
- Willing to provide informed consent.
- Willing to comply with all study procedures and be available for the duration of the study.
- Documented diagnosis of at least one CDI within the last 180 days with treatment completed.
- Currently receiving systemic antibiotics for a non-CDI condition with anticipated duration of no more than 2 weeks.
- Females of childbearing potential must have a negative pregnancy test prior to randomization and agree to use adequate contraception prior to randomization, for the duration of the study, and for 4 weeks following study completion.
- Have received no more than 72 hours of non-CDI antibiotics.
Who cannot join
- History of hypersensitivity or allergy to oral vancomycin.
- Current use of oral vancomycin
- Patients on concurrent treatment with metronidazole or tetracycline monotherapy for any indication
- Patients diagnosed with inflammatory bowel disorder (Crohn's disease), or bacterial gastrointestinal infection cause by agents other than C. difficile (e.g. Salmonella sp.), toxic megacolon and/or known small bowel ileus.
- Dysphagia (inability to swallow capsules) or unwilling to swallow capsules.
- Major gastrointestinal surgery within 3 months of enrollment (does not include appendectomy or cholecystectomy).
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- Any history of total colectomy or bariatric surgery.
- Unable or unwilling to fulfill study requirements.
- Expected life expectancy < 6 months.
- Patients enrolled in another clinical trial with investigational drugs within 30 days prior to randomization.
- Women who are pregnant or breast-feeding.
- Any patient deemed not suitable for study participation at the discretion of the study investigator.
- Diarrhea (3 or more loose stools in a 24 hour period) at enrollment.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Wisconsin-Madison
Madison, Wisconsin, 53705
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
This study evaluates the efficacy of prophylaxis with oral vancomycin for preventing recurrent Clostridium difficile Infection (CDI) in patients who have experienced at least one CDI episode in the last 180 days and are receiving antibiotics for a non CDI condition. Participants will be randomized to receive either placebo or oral vancomycin in addition to their prescribed antibiotic therapy.
Read the detailed description
Many patients who have a CDI experience recurrent or relapsing symptoms. The investigators are studying whether vancomycin in low doses will help prevent further CDI episodes and how this therapy impacts patients' gastrointestinal microbiome and composition.
Patients with a history of past CDI who are receiving antibiotics for a non-CDI condition will be invited to participate. Approximately half of the participants will receive a low-dose capsule of vancomycin and half will receive a placebo. Participants will continue taking the vancomycin/placebo for 5 days after their prescribed antibiotics end.
- Conditions
- Recurrent Clostridium Difficile Infection, Clostridium Difficile Infection, CDI, C.Difficile Diarrhea, C. Diff Colitis, C.Difficile Colitis
- Being tested
- Vancomycin, Placebo
- Keywords
- Oral vancomycin, vancomycin, antibiotic
- Medical subject headings
- Clostridium Infections, Enterocolitis, Pseudomembranous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VancomycinDrug
Also called Vancomycin Hydrochloride, Vancocin
Vancomycin capsule, 125 mg
PlaceboDrug
Capsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule
| Study group | Role | What they receive |
|---|---|---|
| Vancomycin | Experimental | 125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days Receives: Drug: Vancomycin |
| Placebo | Placebo comparator | 125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrent Clostridium Difficile Infection (CDI)
Determine whether CDI recurrence is decreased in patients taking oral vancomycin as prophylactic therapy in addition to standard-of-care antibiotics that patients are taking for non-CDI reasons.
Measured: 8 weeks
Secondary outcomes (3)
Gut Microbiome Composition
Study how the gut microbiome is altered in patients receiving vancomycin treatment compared to placebo.
Measured: 8 weeks
Vancomycin-resistant Enterococcus (VRE) Colonization in Stool Samples of Patients Receiving Vancomycin vs. Patients Receiving Placebo
Low-dose exposure to vancomycin and VRE infection has not been studied. We will examine the incidence of VRE colonization in stool samples of all patients and determine whether oral vancomycin increases the VRE colonization rate, which has a negative impact on the overall health of patients being treated with vancomycin for C. difficile infection.
Measured: 8 weeks
Determine Whether Clostridium Difficile Positivity on Any Stool Sample is a Predictor of CDI Recurrence.
Stool samples will be tested at baseline, at the last dose date of vancomycin or placebo, at approximately 8 weeks following the last dose of vancomycin or placebo, and as indicated for diarrhea symptoms. Samples will be collected and tested for the presence of Clostridium difficile.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2018
- Study start21 May 2018
- Primary completion6 Jul 2023
- Study completion6 Jul 2023
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 Recurrent Clostridium Difficile InfectionStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Medical College of Wisconsin, Agency for Healthcare Research and Quality (AHRQ), Henry Ford Hospital, Mayo Clinic
- Responsible party
- Sponsor
- Investigators
- Nasia Safdar, MD PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03462459
- Sponsor's protocol ID
- 2017-0927
- Other IDs
- 1R01HS025713-01, A534265, SMPH/MEDICINE/INFECT DIS, Protocol ver 6, 18 Nov 2020
- Status last verified
- May 2025
- First submitted
- 28 Feb 2018
- Last updated
- 25 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Keating JA, Xu T, Graham MB, Ramesh M, Khanna S, Dixon J, Kates A, Haight K, Zhao J, Saddler C, Safdar N. Oral Vancomycin for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial. JAMA Netw Open. 2025 Jul 1;8(7):e2517834. doi: 10.1001/jamanetworkopen.2025.17834.
PubMed 40601321
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Oral Vancomycin Prophylaxis for Prevention of Recurrent Clostridium Difficile Infection
- ClinicalTrials.gov ID
- NCT03462459
- Acronym / sponsor ID
- 2017-0927
- Conditions
- Recurrent Clostridium Difficile Infection, Clostridium Difficile Infection, CDI, C.Difficile Diarrhea, C. Diff Colitis, C.Difficile Colitis
- Keywords
- Oral vancomycin, vancomycin, antibiotic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Medical College of Wisconsin, Agency for Healthcare Research and Quality (AHRQ), Henry Ford Hospital, Mayo Clinic
- Study start
- 21 May 2018 (actual)
- Primary completion
- 6 Jul 2023 (actual)
- Study completion
- 6 Jul 2023 (actual)
- First posted
- 12 Mar 2018 (actual)
- Results
- Posted 25 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the efficacy of prophylaxis with oral vancomycin for preventing recurrent Clostridium difficile Infection (CDI) in patients who have experienced at least one CDI episode in the last 180 days and are receiving antibiotics for a non CDI condition. Participants will be randomized to receive either placebo or oral vancomycin in addition to their prescribed antibiotic therapy.
Detailed description
Many patients who have a CDI experience recurrent or relapsing symptoms. The investigators are studying whether vancomycin in low doses will help prevent further CDI episodes and how this therapy impacts patients' gastrointestinal microbiome and composition.
Patients with a history of past CDI who are receiving antibiotics for a non-CDI condition will be invited to participate. Approximately half of the participants will receive a low-dose capsule of vancomycin and half will receive a placebo. Participants will continue taking the vancomycin/placebo for 5 days after their prescribed antibiotics end.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vancomycin | Experimental | Drug: Vancomycin125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days |
| Placebo | Placebo comparator | Drug: Placebo125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Willing to provide informed consent.
- Willing to comply with all study procedures and be available for the duration of the study.
- Documented diagnosis of at least one CDI within the last 180 days with treatment completed.
- Currently receiving systemic antibiotics for a non-CDI condition with anticipated duration of no more than 2 weeks.
- Females of childbearing potential must have a negative pregnancy test prior to randomization and agree to use adequate contraception prior to randomization, for the duration of the study, and for 4 weeks following study completion.
Key exclusion criteria (13 listed)
- History of hypersensitivity or allergy to oral vancomycin.
- Current use of oral vancomycin
- Patients on concurrent treatment with metronidazole or tetracycline monotherapy for any indication
- Patients diagnosed with inflammatory bowel disorder (Crohn's disease), or bacterial gastrointestinal infection cause by agents other than C. difficile (e.g. Salmonella sp.), toxic megacolon and/or known small bowel ileus.
- Dysphagia (inability to swallow capsules) or unwilling to swallow capsules.
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 |
|---|---|---|
| VancomycinAlso: Vancomycin Hydrochloride, VancocinVancomycin capsule, 125 mg | Drug | Vancomycin |
| PlaceboCapsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule | Drug | Placebo |
Primary outcome
Recurrent Clostridium Difficile Infection (CDI)
Time frame: 8 weeks
Determine whether CDI recurrence is decreased in patients taking oral vancomycin as prophylactic therapy in addition to standard-of-care antibiotics that patients are taking for non-CDI reasons.
3 secondary outcomes
Gut Microbiome Composition
Time frame: 8 weeks
Vancomycin-resistant Enterococcus (VRE) Colonization in Stool Samples of Patients Receiving Vancomycin vs. Patients Receiving Placebo
Time frame: 8 weeks
Determine Whether Clostridium Difficile Positivity on Any Stool Sample is a Predictor of CDI Recurrence.
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40601321Keating JA, Xu T, Graham MB, Ramesh M, Khanna S, Dixon J, Kates A, Haight K, Zhao J, Saddler C, Safdar N. Oral Vancomycin for Prevention of Recurrent Clostridioides difficile Infection: A Randomized Clinical Trial. JAMA Netw Open. 2025 Jul 1;8(7):e2517834. doi: 10.1001/jamanetworkopen.2025.17834.
Related trials for Recurrent Clostridium Difficile Infection
Active, not recruitingObservational study
C. Difficile Toxin Levels in Stool From Healthy Individuals Following Standard of Care Antibiotic Treatment for CDI.
Clostridioides Difficile Infection Recurrence
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VE303 for Prevention of Recurrent Clostridioides Difficile Infection
Clostridium Difficile, Clostridium Difficile Infections
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Prevention of Recurrence of Clostridioides Difficile Colitis With Ursodeoxycholic Acid (UCDA) as a Supplement to Standard Therapy
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Evaluation of EXL01, a New Live Biotherapeutic Product to Prevent Recurrence of Clostridioides Difficile Infection in High-risk Patients
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ACX-362E [Ibezapolstat] for Oral Treatment of Recurrent Clostridioides Difficile Infection
Clostridium Difficile Infection Recurrence
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.
Nasia Safdar, MD PhD principal investigator
University of Wisconsin, Madison
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vancomycin in people with Recurrent Clostridium Difficile Infection and Clostridium Difficile Infection, run by University of Wisconsin, Madison 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 6 inclusion and 13 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 May 2025. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 May 2025). 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?
Recurrent Clostridium Difficile Infection (CDI) (time frame: 8 weeks). 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 NCT03462459, 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 May 2025.