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

Phase 2

Completed

• Conditions: Hematologic Diseases; Bone Marrow Transplant; Oncologic Disorders; Clostridium Difficile Infection
• Interventions: Drug: Vancomycin Oral Capsule; Drug: Placebo Oral Capsule

• Registration Number: NCT03030248
• Lead Sponsor: Medical College of Wisconsin

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2017-01-19
• Study First Submitted QC: 2017-01-20
• Study First Posted: 2017-01-24
• Study Start: 2018-06-01
• Primary Completion: 2020-06-30
• Study Completion: 2020-06-30
• Status Verified: 2020-07
• Last Update Submitted: 2020-09-08
• Last Update Posted: 2020-09-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vancomycin treated group	Vancomycin Oral Capsule	This group will be given vancomycin oral capsules, 125 mg, every 6 hours, for 14 days.
Placebo group	Placebo Oral Capsule	This group will be given placebo oral capsules every 6 hours for 14 days.

Primary Outcome Measures

Name	Time	Method
Changes in Clostridium difficile bacterial loads in the stool	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)

Trial Locations

Locations (1)

Froedtert and the Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States