Vancomycin for the Treatment of NAAT(+)/Toxin(-) C. Difficile

Randomized Double Blind Placebo Controlled Trial for the Treatment of NAAT(+)/Toxin EIA(-) Clostridium Difficile

Sponsors

Lead Sponsor: Medical College of Wisconsin

Source Medical College of Wisconsin
Brief Summary

This study proposes to:

1. Characterize the impact of oral vancomycin on C. difficile loads after end of treatment compared to a placebo group.

2. Determine the effect of oral vancomycin on structural and functional microbiome changes after end of treatment compared to a placebo group.

3. Characterize the impact of oral vancomycin against a placebo group on the daily frequency of loose stools by the end of treatment.

Detailed Description

Clostridium difficile infection (CDI) is considered the most frequent healthcare associated infection in the US, causing almost half a million cases per year with an estimated annual cost of 4.8 billion dollars. Despite the existence of a few treatment options against CDI, yearly attributable deaths are estimated at 29,300 in the US. From April 2014 to April 2016, Froedtert Health reported 899 CDIs. Over half of these events are NAAT (Nucleic Acid Amplification Test)(+)/EIA (Enzyme immunoassay)(-) events. To test for CDI, NAAT followed by EIA is used in a Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) and are among the most accurate methods for Clostridium difficile infection (CDI) diagnosis. There is currently uncertainty on how to treat these CDI events.

The primary outcome of this randomized double blind controlled intervention trial will be changes in C. difficile (Clostridium difficile) loads between day 1 and day 14 and changes in C. difficile load between day 14 and day 28. Thirty patients with documented C. difficile will be randomized to either 14 days of vancomycin or placebo capsules. Block randomization will be used to assign patients to the treatment or placebo arms. Randomized assignments will be placed in sealed envelopes which will only be handled by the research pharmacist. Study related stool collections will be obtained on days 1, 7, 14, 21, and 28 (+/- 2days) [Day 1=first day study drug was administered]. Patients will be followed for 90 days starting on day 1. Patients unable to complete at least 7 days of study treatment will be removed from analysis and replaced.

Overall Status Recruiting
Start Date July 17, 2019
Completion Date June 1, 2022
Primary Completion Date June 1, 2021
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Determine the change in C. difficile loads between the vancomycin vs. placebo group. Day 1- Day 28
Determine the long-term persistence of C. difficile from the change in qPCR levels between the vancomycin vs. placebo group Day 1 - Day 90
Secondary Outcome
Measure Time Frame
Characterize the change on structural alterations of the microbiome after end of treatment between the vancomycin vs. placebo groups through 16S rRNA sequencing. Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in bile acids in the oral vancomycin vs. placebo groups by mass spectrometry. Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in amino acids in the oral vancomycin vs. placebo groups by mass spectrometry. Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in sugars in the oral vancomycin vs. placebo groups by mass spectrometry. Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in lipids from Day 1 to Day 90 in the oral vancomycin vs. placebo groups by mass spectrometry. Pre-treatment, Day 1 - Day 90 past the beginning of treatment
Measure the change in frequency of bowel movements in the oral vancomycin vs. placebo groups. Day 1 - Day 90 past the beginning of treatment
Enrollment 30
Condition
Intervention

Intervention Type: Drug

Intervention Name: Vancomycin Oral Capsule

Description: 125 mg capsules every 6 hours for 14 days.

Arm Group Label: Drug: Vancomycin Group

Other Name: Vancocin

Intervention Type: Drug

Intervention Name: Placebo Oral Capsule

Description: Gelatin pill manufactured to mimic 125 mg Vancomycin oral capsule

Arm Group Label: Drug: Placebo Group

Eligibility

Criteria:

Inclusion Criteria:

- Must be at least 18 years of age at time of consent.

- Presence of loose stools triggering clinical C. difficile NAAT/toxin EIA testing.

- Having both C. difficile NAAT (+) and C. difficile toxin EIA (-).

- Admitted outside the hematology-oncology unit.

- Must be willing to keep a study supplied drug diary

Exclusion Criteria:

- Presence of sepsis. Sepsis will be defined as a Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more as per 2016 definitions.

- Inability to take oral medications.

- Unwillingness or inability to provide written informed consent.

- Has a documented allergy to vancomycin.

- Has a documented life expectancy shorter than treatment course (14 days).

- Unwilling or unable to collect stool samples in the outpatient setting after discharge.

- Diagnosis of C. difficile colitis [NAAT(+) and toxin EIA(+)] in the preceding 3 months from enrollment.

- Received oral vancomycin during their current hospitalization, excluding empiric treatment given while pending C. difficile NAAT/toxin EIA results. Intravenous vancomycin is not an exclusion criterion.

- Women known to be pregnant or lactating during the study.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Silvia Munoz-Price, M.D., Ph.D. Principal Investigator Medical College of Wisconsin
Overall Contact

Last Name: Silvia Munoz-Price, M.D., Ph.D.

Phone: (414) 955-0483

Email: [email protected]

Location
Facility: Status: Contact: Medical College of Wisconsin, Inc. Silvia Munoz-Price, M.D., Ph.D. 414-955-0483 [email protected]
Location Countries

United States

Verification Date

October 2019

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Drug: Vancomycin Group

Type: Active Comparator

Description: Subjects will receive oral vancomycin capsules by mouth, 125 mg every 6 hours for 14 days.

Label: Drug: Placebo Group

Type: Placebo Comparator

Description: Subjects will receive a placebo oral capsule by mouth every 6 hours for 14 days. The placebo oral capsule is manufactured by Study Site's pharmacy to be identical in size, shape, color, appearance and taste as the drug comparator

Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Patients will be divided into 2 groups, one receiving oral vancomycin and the other placebo.

Primary Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Masking Description: After enrollment, patients will be randomized to treatment with vancomycin 125 mg capsules by mouth every 6 hours for 14 days or to placebo with identical looking capsules for the same length of treatment. Block randomization will be used to assign patients to the treatment or placebo arms. Randomized assignments will be placed in sealed envelopes which will only be handled by the research pharmacist. Clinical providers, research team, and patients will remain blinded to allocation

Source: ClinicalTrials.gov