TOX NEG Trial: Clostridium Difficile Diagnosis and Treatment

NCT03388268 | Completed Phase 4 Results FDA Drug FDA Device

• 1 other identifier: 201708055
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the risks and benefits of antibiotic treatment for Clostridium difficile infection (CDI) among patients whose stool samples are nucleic acid amplification test (NAAT) positive and enzyme immunoassay (EIA) negative for C. difficile. Currently, healthcare facilities use a wide variety of tests and strategies for identifying patients with CDI; both EIA and NAAT are widely used. There is no clear gold standard for identifying CDI. At WUSM and BJH, patients are only treated for CDI if they have a positive EIA. However, at many other healthcare facilities, the standard of care is to treat for CDI if the patient is NAAT positive. Some patients who are NAAT-positive may not have true CDI; while this treatment is standard of care at many facilities, the risk and benefits of treating these patients for CDI is unknown. We propose to perform a double blinded, randomized controlled non-inferiority trial of antimicrobial of patients who are EIA negative, NAAT positive to determine the risks and benefits of CDI treatment in this population.

Conditions

Clostridium Difficile Infection; Diarrhea

Keywords

Clostridium difficile; Diarrhea

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Detectable C. Difficile

  Stool specimens will be examined via culture and metagenomic analyses for the presence of detectable C. difficile. Presence will be defined as presence of culturable C. difficile in stool any time after collection of enrollment stool samples.

  Through 8 weeks after completion of study drug

Secondary Outcomes (3)

• Number of Participants With Detectable Environmental Contamination

  Through 8 weeks after completion of study drug

• Duration of Diarrhea in Study Participants as Defined by Daily Symptoms and Questionnaire Using the Bristol Stool Chart

  Through 8 weeks after completion of study drug

• Presence of Other Multidrug Resistant Organisms in the Gut Microbiome of Study Participants

  Through 8 weeks after completion of the study drug

Study Arms (2)

Oral vancomycin

ACTIVE COMPARATOR

125mg of oral vancomycin four times per day

Drug: Oral Vancomycin; Device: Toxin enzyme immunoassay; Device: Nuceleic acid amplification test

Placebo

PLACEBO COMPARATOR

Placebo four times per day

Drug: Placebo; Device: Toxin enzyme immunoassay; Device: Nuceleic acid amplification test

Interventions

Oral Vancomycin DRUG

Oral vancomycin 125mg 4 times per day

Also known as: Vancocin

Oral vancomycin

Placebo DRUG

Sugar liquid manufactured to mimic oral vancomycin 125mg

Placebo

Toxin enzyme immunoassay DEVICE

EIA assay: Wampole/Tech Lab Tox A/B II

Oral vancomycin; Placebo

Nuceleic acid amplification test DEVICE

NAAT: Xpert C. difficile, Cepheid

Oral vancomycin; Placebo

Eligibility Criteria

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

You may qualify if:

• Stool submitted to the BJH microbiology laboratory for C. difficile testing that tests negative for C. difficile toxins (C. difficile Tox A/B II, Alere, Waltham, MA) as part of routine clinical care and positive by NAAT (Xpert C. difficile, Cepheid, Sunnyvale, CA)
• Clinically significant diarrhea (≥3 diarrheal bowel movements per day or ≥1 diarrheal bowel movement plus abdominal pain)
• ≥18 years of age.

You may not qualify if:

• The presence of a condition associated with persistent / prolonged / recurrent diarrhea, including, but not limited to:
• Upcoming chemotherapy
• Previous or upcoming bone marrow/hematopoietic stem cell transplant,
• Leukemia: new, not in remission, or receiving chemotherapy
• Inflammatory bowel disease
• Crohn's disease
• Ulcerative colitis
• Microscopic colitis
• Previous total colectomy
• Previous partial colectomy without return to formed bowel movement or previous resection of colon
• Colostomy or ileostomy
• Unable to follow study procedures
• Not expected to survive until study follow-up is complete
• Allergy or intolerance to oral vancomycin
• A history of CDI in the past 3 months

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Clostridium Infections; Diarrhea

Interventions

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)

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

Results Point of Contact

• Title: Kimberly Reske, MPH, Research Coordinator
• Organization: Washington University in St. Louis

kreske@wustl.edu

314-747-4041

Study Officials

• Erik Dubberke, MD, MSPH

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blinded randomized controlled trial of CDI treatment with oral vancomycin vs. placebo

Study Record Dates

• First Submitted: December 5, 2017
• First Posted: January 2, 2018
• Study Start: December 29, 2017
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: July 26, 2021
• Results First Posted: July 23, 2021

Record last verified: 2021-07

Locations

US (1)