Enteral Vancomycin as Primary Prophylaxis Against Clostridioides Difficile Infection in Critically Ill Patients

NCT07221370 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRBNet #: 2114799-4
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine if oral vancomycin can prevent C.diff infection in adults who are critically ill and are at high risk of C.diff infection due to their medical conditions and being in the hospital. It will also help us learn about the safety of the drug in this setting. The main questions the trial aims to answer are:

• Does oral vancomycin lower the rate of C.diff infection in high-risk patients?
• Does C.diff carrier status change the C.diff infection rate as well as clearance of carrier status when vancomycin is used as primary prophylaxis? Researchers will compare the oral, active drug vancomycin to a placebo (a look-alike substance that contains no drug) to determine if vancomycin works to prevent C.diff infection in the hospital. Participants will:
• Take oral vancomycin or a placebo while they receive systemic antibiotic(s) for up to five days after the last dose of said systemic antibiotic(s). The treatment of said systemic antibiotic(s) is not to exceed 21 days.
• When discharged from the hospital, participants will continue to take the study medication in the event he/she did not complete the intended course of the study medication while in the hospital.
• Participants will provide stool sample or rectal swabs for to assess their C.diff carrier status as well as any change in stool microbiome status, including VRE (vancomycin resistant Enterococcus)
• After completion of the intervention period, participants will be contacted via telephone to assess if they developed diarrhea or any untoward effects of study medication.

Conditions

Clostridium Difficile Infection; Vancomycin Resistant Enterococci Infection

Keywords

Clostridium difficle infection; primary prophylaxis; Vancomycin resistant enterocci infection

Outcome Measures

Primary Outcomes (1)

• Incidence the rate of healthcare facility-onset Clostridioides dificile infection (CDFO-CFI).

  Incidence of HCFO-CDI, defined as symptoms of ≥ 3 loose stools or diarrhea (in the absence of laxatives or other non-CDI causes) in a 24-hour period in subjects with concurrent positive stool test for C. difficile (polymerase chain reaction \[PCR\] and stool toxin test) \> 72 hours into hospitalization.

  up to 4 months

Secondary Outcomes (6)

• Incidence of Vancomycin Resistance Enterococcus (VRE) colonization in stool sample.

  up to 30 days

• Rate community onset healthcare facility-associated CDI.

  up to 90 days

• Time to Clostridioides difficile infection in symptomatic patients

  up to 30 days

• Clostridioides difficile colonization at discharge (PCR and toxin)

  up to 30 days

• Hospital length of stay (day)

  up to 30 days

Other Outcomes (4)

• Stratification of study populaton based on B1/NAP1/027 gene at baseline

  up to 120 days

• Stratification of study population based on age

  up to 120 days

• Stratification of study population based on use of vasopressor

  up to 30 days

Study Arms (2)

Oral Vancomycin 125 mg (liquid)

ACTIVE COMPARATOR

Oral Vancomycin 125 mg (liquid) daily

Drug: Vancomycin 125mg

Placebo oral (liquid)

PLACEBO COMPARATOR

Oral Placebo (liquid) daily.

Drug: Placebo

Interventions

Vancomycin 125mg DRUG

Vancomycin 125 mg orally daily

Oral Vancomycin 125 mg (liquid)

Placebo DRUG

Syrup solution used to mixed with Vancomycin will be used in equal volume to be the placebo comparator.

Placebo oral (liquid)

Eligibility Criteria

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

You may qualify if:

• Must meet all 3 criteria:
• Adults aged 18 years and older.
• Receiving ≥ 72 hours of a systemic antibiotic during index hospitalization.
• Admitted ≥ 72 hours into their index hospitalization.
• And must meet 2 additional of the following high-risk criteria
• Age ≥ 65 years
• Previous residence in long-term care facility
• Previous proton pump inhibitor use (chronic or as needed)
• Inflammatory bowel disease
• Immunocompromised state (HIV/AIDS; transplant recipient; receipt of prednisone 20 mg daily for at least one month, immunosuppressants, or chemotherapy)
• End stage renal disease (ESRD)
• Diabetes mellitus
• Receipt of catecholamines (norepinephrine at a rate of ≥ 5 mcg/min)
• Hospitalized ≤ 30 days prior to the index hospitalization.
• Received systemic antibiotics during that prior hospitalization.

You may not qualify if:

• Pregnant or breastfeeding women
• Currently incarcerated individuals
• Individual or legal representative whose informed consent cannot be obtained
• Subject not expected to survive the ICU stay or subject likely to be considered for palliative or hospice care
• Receiving concurrent treatment with metronidazole for any indication
• Receiving concurrent probiotics
• Allergic reaction or had a contraindication for use of enteral vancomycin
• History of prior CDI within the past 90 days of randomization
• Infection requiring more than 14 21 days of systemic antibiotics during index hospitalization

Sponsors & Collaborators

• Riverside University Health System Medical Center: lead

Study Sites (1)

Riverside University Health System

Moreno Valley, California, 92373, United States

RECRUITING

Related Publications (16)

• Abt MC, McKenney PT, Pamer EG. Clostridium difficile colitis: pathogenesis and host defence. Nat Rev Microbiol. 2016 Oct;14(10):609-20. doi: 10.1038/nrmicro.2016.108. Epub 2016 Aug 30.

  PMID: 27573580 BACKGROUND

• Bobo LD, Dubberke ER, Kollef M. Clostridium difficile in the ICU: the struggle continues. Chest. 2011 Dec;140(6):1643-1653. doi: 10.1378/chest.11-0556.

  PMID: 22147824 BACKGROUND

• Rineh A, Kelso MJ, Vatansever F, Tegos GP, Hamblin MR. Clostridium difficile infection: molecular pathogenesis and novel therapeutics. Expert Rev Anti Infect Ther. 2014 Jan;12(1):131-50. doi: 10.1586/14787210.2014.866515.

  PMID: 24410618 BACKGROUND

• Zhang S, Palazuelos-Munoz S, Balsells EM, Nair H, Chit A, Kyaw MH. Cost of hospital management of Clostridium difficile infection in United States-a meta-analysis and modelling study. BMC Infect Dis. 2016 Aug 25;16(1):447. doi: 10.1186/s12879-016-1786-6.

  PMID: 27562241 BACKGROUND

• Vedantam G, Clark A, Chu M, McQuade R, Mallozzi M, Viswanathan VK. Clostridium difficile infection: toxins and non-toxin virulence factors, and their contributions to disease establishment and host response. Gut Microbes. 2012 Mar-Apr;3(2):121-34. doi: 10.4161/gmic.19399. Epub 2012 Mar 1.

  PMID: 22555464 BACKGROUND

• Lemiech-Mirowska E, Michalkiewicz M, Sierocka A, Gaszynska E, Marczak M. The Hospital Environment as a Potential Source for Clostridioides difficile Transmission Based on Spore Detection Surveys Conducted at Paediatric Oncology and Gastroenterology Units. Int J Environ Res Public Health. 2023 Jan 15;20(2):1590. doi: 10.3390/ijerph20021590.

  PMID: 36674344 BACKGROUND

• Kochan TJ, Foley MH, Shoshiev MS, Somers MJ, Carlson PE, Hanna PC. Updates to Clostridium difficile Spore Germination. J Bacteriol. 2018 Jul 25;200(16):e00218-18. doi: 10.1128/JB.00218-18. Print 2018 Aug 15.

  PMID: 29760211 BACKGROUND

• Gil F, Lagos-Moraga S, Calderon-Romero P, Pizarro-Guajardo M, Paredes-Sabja D. Updates on Clostridium difficile spore biology. Anaerobe. 2017 Jun;45:3-9. doi: 10.1016/j.anaerobe.2017.02.018. Epub 2017 Feb 22.

  PMID: 28254263 BACKGROUND

• Paredes-Sabja D, Shen A, Sorg JA. Clostridium difficile spore biology: sporulation, germination, and spore structural proteins. Trends Microbiol. 2014 Jul;22(7):406-16. doi: 10.1016/j.tim.2014.04.003. Epub 2014 May 7.

  PMID: 24814671 BACKGROUND

• Martinez-Melendez A, Cruz-Lopez F, Morfin-Otero R, Maldonado-Garza HJ, Garza-Gonzalez E. An Update on Clostridioides difficile Binary Toxin. Toxins (Basel). 2022 Apr 27;14(5):305. doi: 10.3390/toxins14050305.

  PMID: 35622552 BACKGROUND

• Johnson SW, Brown SV, Priest DH. Effectiveness of Oral Vancomycin for Prevention of Healthcare Facility-Onset Clostridioides difficile Infection in Targeted Patients During Systemic Antibiotic Exposure. Clin Infect Dis. 2020 Aug 22;71(5):1133-1139. doi: 10.1093/cid/ciz966.

  PMID: 31560051 BACKGROUND

• Papic N, Maric LS, Vince A. Efficacy of oral vancomycin in primary prevention of Clostridium Difficile infection in elderly patients treated with systemic antibiotic therapy. Infect Dis (Lond). 2018 Jun;50(6):483-486. doi: 10.1080/23744235.2018.1425551. Epub 2018 Jan 11. No abstract available.

  PMID: 29323607 BACKGROUND

• DailyMed - FIRVANQ- vancomycin hydrochloride kit. Accessed September 7, 2023. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5aca5508-b577-446c-9980-ab4c7582b4b9

  BACKGROUND

• Fishbein SRS, Hink T, Reske KA, Cass C, Struttmann E, Iqbal ZH, Seiler S, Kwon JH, Burnham CA, Dantas G, Dubberke ER. Randomized Controlled Trial of Oral Vancomycin Treatment in Clostridioides difficile-Colonized Patients. mSphere. 2021 Jan 13;6(1):e00936-20. doi: 10.1128/mSphere.00936-20.

  PMID: 33441409 BACKGROUND

• Ganetsky A, Han JH, Hughes ME, Babushok DV, Frey NV, Gill SI, Hexner EO, Loren AW, Luger SM, Mangan JK, Martin ME, Smith J, Freyer CW, Gilmar C, Schuster M, Stadtmauer EA, Porter DL. Oral Vancomycin Prophylaxis Is Highly Effective in Preventing Clostridium difficile Infection in Allogeneic Hematopoietic Cell Transplant Recipients. Clin Infect Dis. 2019 May 30;68(12):2003-2009. doi: 10.1093/cid/ciy822.

  PMID: 30256954 BACKGROUND

• Maraolo AE, Mazzitelli M, Zappulo E, Scotto R, Granata G, Andini R, Durante-Mangoni E, Petrosillo N, Gentile I. Oral Vancomycin Prophylaxis for Primary and Secondary Prevention of Clostridioides difficile Infection in Patients Treated with Systemic Antibiotic Therapy: A Systematic Review, Meta-Analysis and Trial Sequential Analysis. Antibiotics (Basel). 2022 Jan 30;11(2):183. doi: 10.3390/antibiotics11020183.

  PMID: 35203786 BACKGROUND

MeSH Terms

Conditions

Clostridium Infections

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Suman Thapamagar, MD

CONTACT

9514864000; suman.thapamagar@ruhealth.org

Brian Phan, PharmD

CONTACT

9514864000; b.phan@ruhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Asst Prof of Medicine

Model Details: Randomized Double Blind Placebo-controlled trial.

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: October 27, 2025
• Study Start: October 21, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (1)