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Completed

NCT Number: NCT03827447

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

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.

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Key information

Conditions

Clostridium Difficile Infection Bacterial Infections Bacterial Infections and Mycoses Clostridium Infections Gram-Positive Bacterial Infections Infections

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, 53226, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Vancomycin Oral Capsule

Drug

125 mg capsules every 6 hours for 14 days.

Other names: Vancocin

Placebo oral capsule

Drug

Gelatin pill manufactured to mimic 125 mg Vancomycin oral capsule

Primary outcomes

  1. Determine the change in C. difficile loads between the vancomycin vs. placebo group.

    Time frame: Day 1- Day 28

    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).

  2. 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

    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.

Secondary outcomes

  1. 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

    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.

  2. 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

    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.

  3. 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

    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.

  4. 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

    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.

  5. 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

    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.

  6. 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

    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.

Sponsors and collaborators

Lead sponsor

Medical College of Wisconsin

Other

Registry information

Official study title

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

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Feb 1, 2019
Registry last updated
Oct 20, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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