- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03827447
Vancomycin for the Treatment of NAAT(+)/Toxin(-) C. Difficile
Randomized Double Blind Placebo Controlled Trial for the Treatment of NAAT(+)/Toxin EIA(-) Clostridium Difficile
This study proposes to:
- Characterize the impact of oral vancomycin on C. difficile loads after end of treatment compared to a placebo group.
- Determine the effect of oral vancomycin on structural and functional microbiome changes after end of treatment compared to a placebo group.
- Characterize the impact of oral vancomycin against a placebo group on the daily frequency of loose stools by the end of treatment.
Study Overview
Status
Conditions
Intervention / 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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Medical College of Wisconsin, Inc.
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: TRIPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
ACTIVE_COMPARATOR: Drug: Vancomycin Group
Subjects will receive oral vancomycin capsules by mouth, 125 mg every 6 hours for 14 days.
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125 mg capsules every 6 hours for 14 days.
Other Names:
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PLACEBO_COMPARATOR: Drug: Placebo Group
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
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Gelatin pill manufactured to mimic 125 mg Vancomycin oral capsule
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine the change in C. difficile loads between the vancomycin vs. placebo group.
Time Frame: Day 1- Day 28
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Compare the impact of vancomycin vs placebo on changes in C. difficile load from stool samples collected on Day 1 to end-of-treatment (Day 14) and to Day 28 using quantitative Polymerase Chain Reaction (qPCR).
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Day 1- Day 28
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Determine the long-term persistence of C. difficile from the change in qPCR levels between the vancomycin vs. placebo group
Time Frame: Day 1 - Day 90
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Establish the long-term persistence of C. difficile by qPCR from stool samples collected at Day 1, 7, 14, 21, 28, and 90 between the vancomycin and placebo group.
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Day 1 - Day 90
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
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.
Time Frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Structural alterations of the microbiome after end of treatment will be determined using 16S rRNA sequencing from stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 & 90.
Structural alterations will be defined according to the Shannon Diversity Index.
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Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Measure the change in bile acids in the oral vancomycin vs. placebo groups by mass spectrometry.
Time Frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring bile acids.
They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 & 90.
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Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Measure the change in amino acids in the oral vancomycin vs. placebo groups by mass spectrometry.
Time Frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring amino acids.
They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 & 90.
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Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Measure the change in sugars in the oral vancomycin vs. placebo groups by mass spectrometry.
Time Frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring sugars.
They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 & 90.
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Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Measure the change in lipids from Day 1 to Day 90 in the oral vancomycin vs. placebo groups by mass spectrometry.
Time Frame: Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Characterize the impact of oral vancomycin against placebo on functional microbiome changes after end of treatment by measuring lipids.
They will be measured via mass spectrometry using stool samples collected upon diagnosis, Days 1, 7, 14, 21, 28 & 90.
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Pre-treatment, Day 1 - Day 90 past the beginning of treatment
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Measure the change in frequency of bowel movements in the oral vancomycin vs. placebo groups.
Time Frame: Day 1 - Day 90 past the beginning of treatment
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Characterize the impact of oral vancomycin against a placebo group on the daily frequency of bowel movements by the end of treatment.
This scale goes from 0 to >20 in increments of 1. Data will be analyzed over time as a slope for each patient.
The closer to 1 per 24 hours the better the outcome.
Data will be obtained from patient self-reports using study questionnaires on Days 1, 7, 14, 21, 28 & 90.
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Day 1 - Day 90 past the beginning of treatment
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRO00033844
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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