Vancomycin for C Difficile NAAT+/EIA- Hematology Oncology Patients

Study Overview
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Brief Summary
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This study will randomized hematology oncology patients with active diarrhea and a NAAT positive/toxin EIA negative to either 14 days of oral vancomycin capsules or placebo. The study is designed to include 30 patients (15 per arm). Outcomes will include C. difficile load using qPCR, VRE loads, structural and functional microbiome changes and frequency of bowel movements. All endpoints will be measured at several time points including days 0, 14, 21 and 90.

Detailed Description
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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.

Official Title
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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

Conditions
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Clostridium Difficile Infection, Hematologic Diseases, Bone Marrow Transplant, Oncologic Disorders

Intervention / Treatment
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* Drug: Vancomycin Oral Capsule
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to the hematology oncology inpatient units at Froedtert Memorial Lutheran Hospital 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 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 Pregnancy or lactating

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be divided into two groups, one receiving oral vancomycin capsules, the other receiving oral placebo capsules.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vancomycin treated group<br>This group will be given vancomycin oral capsules, 125 mg, every 6 hours, for 14 days. | Drug: Vancomycin Oral Capsule<br>* 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.<br>* Other names: Vancocin hydrochloride Oral Capsule;|
| Placebo Comparator: Placebo group<br>This group will be given placebo oral capsules every 6 hours for 14 days. | Drug: Placebo Oral Capsule<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiome, bone marrow transplantation, Clostridium difficile, metabolomics, vancomycin