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Treatment of Clostridium Difficile in Colonized Patients in the Hematology Oncology Population

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03030248
Recruitment Status : Not yet recruiting
First Posted : January 24, 2017
Last Update Posted : November 30, 2017
The Jackson Laboratory for Genomic Medicine
Information provided by (Responsible Party):
Medical College of Wisconsin

Brief Summary:

There is good evidence that randomizing C. difficile NAAT(+), toxin(-) patients to non-treatment represents an ethically tolerable risk-benefit, even in cancer patients and hematopoetic stem cell transplant (HSCT) recipients. Actually, detection of free toxin in the stool was the standard of care for the diagnosis of C. difficile infection (CDI) from 1983 through 2010. Since then, NAAT became the standard diagnostic test for over 60% of US hospitals (National Healthcare Safety Network, unpublished data). However, there is growing evidence that symptomatic patients who are NAAT(+), toxin(-) have outcomes similar to patients who are NAAT(-), toxin(-); some of these outcomes include 30-day mortality, ICU admission, and hospital readmission triggered by C. difficile. Furthermore, the United Kingdom has successfully used a similar two step diagnostic algorithm with a confirmatory toxin EIA since 2012.

The adverse health consequences resulting from antibiotic overtreatment of NAAT(+), toxin(-) patients may be particularly important in transplant recipients. The usual treatment prescribed for CDI at the Froedtert Memorial Lutheran Hospital is oral vancomycin. While this drug has excellent activity against C. difficile and commonly suppresses its growth to non-detection, it does not eradicate carriage and its use results in marked and prolonged disruption of the lower intestinal microbiota. Meanwhile, the degree of lower intestinal microbiota disruption at the time of HSCT engraftment has been demonstrated to be an independent predictor (controlling for other markers of underlying disease) of overall and transplant-related 3-year mortality.14 In addition, recent findings suggest that bone marrow suppressive effects of antibiotics, in this case potentially unnecessary oral vancomycin (which is not appreciably absorbed), may be solely mediated via microbiota disruption. All these data supports the notion that antibiotic treatment of NAAT(+), toxin(-) C. difficile patients might have significant negative repercussions without a clear clinical benefit.

Condition or disease Intervention/treatment Phase
Clostridium Difficile Infection Drug: Vancomycin Oral Capsule Drug: Placebo Oral Capsule Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients will be divided into two groups, one receiving oral vancomycin capsules, the other receiving oral placebo capsules.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: The allocation status of patients within this study will be held in sealed envelopes by the research pharmacist on the team. Neither the main care provider, study physicians, or the patient will know of their group, until either the end of the study (after data analysis).
Primary Purpose: Treatment
Official Title: Randomized Double Blind Controlled Trial for the Treatment of Nucleic Acid Amplification Test (NAAT)+/Toxin Enzyme Immunoassay (EIA)- Clostridium Difficile in the Hematology Oncology Population
Estimated Study Start Date : February 1, 2018
Estimated Primary Completion Date : May 31, 2019
Estimated Study Completion Date : May 31, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Vancomycin treated group
This group will be given vancomycin oral capsules, 125 mg, every 6 hours, for 14 days.
Drug: Vancomycin Oral Capsule
We have chosen oral vancomycin capsules as it is currently a standard of care for Clostridium difficile infections, is poorly absorbed by the intestines, and is easier to blind compared to oral vancomycin solution.
Other Name: Vancocin hydrochloride Oral Capsule

Placebo Comparator: Placebo group
This group will be given placebo oral capsules every 6 hours for 14 days.
Drug: Placebo Oral Capsule
A capsule containing gelatin, polyethylene glycol, titanium dioxide, iron oxide, and FD&C blue No. 2. Contains the inactive ingredients of the vancomycin oral capsule, as mixed by the Froedtert Health Research Pharmacy.

Primary Outcome Measures :
  1. Changes in Clostridium difficile bacterial loads in the stool [ Time Frame: Pre-treatment, 1, 7, 14, 21, 28, and 90 days past the beginning of treatment ]
    Changes in Clostridium difficile bacterial counts from stool as determined by quantitative polymerase chain reaction (PCR)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients admitted to the hematology oncology inpatient units at Froedtert Memorial Lutheran Hospital
  • Having had a bone marrow transplantation (stem cell transplant) within the past 24 months
  • Positive C. difficile surveillance test (NAAT) upon unit admission
  • New onset of diarrhea during hospitalization
  • C. difficile clinical testing showing NAAT positive EIA negative results

Exclusion Criteria:

  • Being unable to consent for self
  • Inability to take enteral medications
  • Unwillingness to enroll in study
  • Patient has a documented allergy to vancomycin
  • Patient has a documented life expectancy shorter than treatment course (14 days)
  • Patient is unwilling or unable to provide stool samples in the outpatient setting after discharge
  • Diagnosis of C. difficile colitis [NAAT (+) and toxin EIA (+) within 3 months of enrollment).
  • New onset of fever within 24 hours prior to the onset of diarrhea during index admission
  • New onset of abdominal distention within 24 hours prior to the onset of diarrhea during index admission
  • Presence of toxic megacolon
  • Presence of clinical sepsis. Sepsis will be defined as a Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more as per 2016 definitions
  • Absolute neutrophil count <500

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03030248

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Contact: Silvia Munoz-Price, M.D., Ph.D. (414) 955-8020

Sponsors and Collaborators
Medical College of Wisconsin
The Jackson Laboratory for Genomic Medicine
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Principal Investigator: Silvia Munoz-Price, M.D., Ph.D. Medical College of Wisconsin

Publications of Results:
Other Publications:
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Responsible Party: Medical College of Wisconsin Identifier: NCT03030248     History of Changes
Other Study ID Numbers: PRO00028749
First Posted: January 24, 2017    Key Record Dates
Last Update Posted: November 30, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Participant data to be shared would consist of age categories, genders, treatment groups, Clostridium difficile status, microbiome profile and metabolic profile. The data will be anonymized to prevent the identification of individual patients from the data provided. The data would be made available through contacting the principal investigator directly.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Clostridium Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Anti-Infective Agents