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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HS025713-01 | U.S. AHRQ Grant/Contract | View source | |
| A534265 | Other Identifier | UW, Madison | |
| SMPH/MEDICINE/INFECT DIS | Other Identifier | UW, Madison | |
| Protocol ver 6, 18 Nov 2020 | Other Identifier | UW Madison |
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| Name | Class |
|---|---|
| Medical College of Wisconsin | OTHER |
| Agency for Healthcare Research and Quality (AHRQ) | FED |
| Henry Ford Hospital | OTHER |
| Mayo Clinic |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vancomycin | Experimental | 125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days |
|
| Placebo | Placebo Comparator | 125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vancomycin | Drug | Vancomycin capsule, 125 mg |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Gut Microbiome Composition | Study how the gut microbiome is altered in patients receiving vancomycin treatment compared to placebo. | 8 weeks |
| Vancomycin-resistant Enterococcus (VRE) Colonization in Stool Samples of Patients Receiving Vancomycin vs. Patients Receiving Placebo |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nasia Safdar, MD PhD | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Wisconsin-Madison | Madison | Wisconsin | 53705 | United States | ||
| Medical College of Wisconsin |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40601321 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Vancomycin | 125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days Vancomycin: Vancomycin capsule, 125 mg |
| FG001 | Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 26, 2021 |
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| OTHER |
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| Placebo | Drug | Capsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule |
|
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. |
| 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. | 8 weeks |
| Milwaukee |
| Wisconsin |
| 53226 |
| United States |
125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days
Placebo: Capsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule
| COMPLETED |
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| NOT COMPLETED |
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Adults age 18 or older with a diagnosis of recurrent Clostridioides diffcile infection
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| ID | Title | Description |
|---|---|---|
| BG000 | Vancomycin | 125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days Vancomycin: Vancomycin capsule, 125 mg |
| BG001 | Placebo | 125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days Placebo: Capsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 8 weeks |
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| Secondary | Gut Microbiome Composition | Study how the gut microbiome is altered in patients receiving vancomycin treatment compared to placebo. | Posted | Count of Units | stool samples | 8 weeks | stool samples | stool samples |
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| Secondary | 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. | Posted | Count of Participants | Participants | 8 weeks |
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| Secondary | 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. | Posted | Count of Units | stool samples | 8 weeks | stool samples | stool samples |
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8 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vancomycin | 125 mg, oral capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days Vancomycin: Vancomycin capsule, 125 mg | 1 | 37 | 9 | 37 | 37 | 37 |
| EG001 | Placebo | 125 mg placebo capsule by mouth, once daily, for the duration of standard-of-care antibiotic therapy plus 5 days Placebo: Capsule containing inert (nonactive) material to mimic 125 mg vancomycin capsule | 2 | 42 | 10 | 42 | 42 | 42 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia with associated shock | Infections and infestations | SNOMED CT | Systematic Assessment |
| |
| Bacteremia/Sepsis | Infections and infestations | SNOMED CT | Systematic Assessment |
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| Elevated liver function tests due to transplant | Gastrointestinal disorders | SNOMED CT | Systematic Assessment | Elevated liver function tests secondary to transplant |
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| Recurrent C difficile Infection (rCDI) | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
| |
| Septic shock | Infections and infestations | SNOMED CT | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
| |
| Sickle Cell Pain Crisis | Blood and lymphatic system disorders | SNOMED CT | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
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| Cellulitis | Infections and infestations | SNOMED CT | Systematic Assessment | Right arm |
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| Thrombophlebitis | Infections and infestations | SNOMED CT | Systematic Assessment | Right arm |
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| Nausea | Gastrointestinal disorders | SNOMED CT | Systematic Assessment | Post chemotherapy |
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| Vomiting | Gastrointestinal disorders | SNOMED CT | Systematic Assessment | Post chemotherapy |
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| Nausea | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
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| Congestive Heart Failure Exacerbation | Cardiac disorders | SNOMED CT | Systematic Assessment |
| |
| Whipple Procedure | Surgical and medical procedures | SNOMED CT | Systematic Assessment | Planned hospitalization for procedure |
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| General weakness/malaise | General disorders | SNOMED CT | Systematic Assessment | Hospitalization due to general weakness/malaise |
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| Toe Infection | Infections and infestations | SNOMED CT | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | SNOMED CT | Systematic Assessment |
| |
| Altered Mental Status | Psychiatric disorders | SNOMED CT | Systematic Assessment | Multifactorial Altered Mental Status |
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| Traumatic fall with sequelae | Injury, poisoning and procedural complications | SNOMED CT | Systematic Assessment |
| |
| Carotid endarctectomy with stents | Vascular disorders | SNOMED CT | Systematic Assessment |
| |
| Peripheral autologous stem cell transplant | Surgical and medical procedures | SNOMED CT | Systematic Assessment | Planned procedure due to stem cell transplant |
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| Sigmoid resection surgery | Surgical and medical procedures | SNOMED CT | Systematic Assessment | Sigmoid resection due to diverticulitis |
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| Vaginal Polyp | Reproductive system and breast disorders | SNOMED CT | Systematic Assessment |
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| Heart Failure | Cardiac disorders | SNOMED CT | Systematic Assessment | New onset ACC/AHA Stage C HFpEF |
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| Urinary Tract Infection | Infections and infestations | SNOMED CT | Systematic Assessment |
| |
| Small bowel obstruction | Gastrointestinal disorders | SNOMED CT | Systematic Assessment | Small bowel obstruction secondary to colon cancer |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal disorders | Gastrointestinal disorders | SNOMED CT | Systematic Assessment | Diarrhea |
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| Fever/Flu-Like Symptoms | General disorders | SNOMED CT | Systematic Assessment | Fever/Flu-Like Symptoms |
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| UTI | Infections and infestations | SNOMED CT | Systematic Assessment | Urinary tract infection |
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| Infections | Infections and infestations | SNOMED CT | Systematic Assessment | Infections |
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| Joint pain and swelling | Musculoskeletal and connective tissue disorders | SNOMED CT | Systematic Assessment | Joint pain and swelling |
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| Abdominal Pain/Discomfort | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
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| Nausea/Vomiting | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
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| Bloating/flatulence | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
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| Bloody stool/loose stool | Gastrointestinal disorders | SNOMED CT | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Nasia Safdar, Professor | University of Wisconsin-Madison | 608-265-1545 | ns2@medicine.wisc.edu |
| Nov 1, 2024 |
| Prot_SAP_007.pdf |
| ICF | No | No | Yes | Informed Consent Form | Oct 10, 2019 | Nov 1, 2024 | ICF_008.pdf |
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| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| D004761 | Enterocolitis, Pseudomembranous |
| ID | Term |
|---|---|
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D004760 | Enterocolitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D014640 | Vancomycin |
| ID | Term |
|---|---|
| D006020 | Glycopeptides |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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Statistical analyses are primarily reported for the population who were randomized in the study ("as randomized"). The secondary statistical analyses are reported for the population who completed all three visits ("as completed treatment"). Proportional tests were conducted to compare the episodes of C. difficile recurrence in eight weeks following the completion of the study intervention in patients receiving vancomycin versus placebo using the Chi-squared test. Log-rank tests were conducted to compare the non-recurrence proportions within the eight-week period in patients receiving vancomycin versus placebo with the Kaplan-Meier method. A nonparametric Wilcoxon rank sum test was used to compare distributions of the number of days to the first recurrence of CDI after starting oral vancomycin or placebo. The significance level was set to be ≤0.05. All statistical analyses were conducted in R statistical software (version 4.4.0; R Core Team, 2024) |
| stool samples |
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| stool samples |
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