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

Medical College of Wisconsin

Status and phase: Completed; Phase 1

Conditions: Clostridium Difficile Infection

Treatments: Drug: Vancomycin Oral Capsule; Drug: Placebo Oral Capsule

Study type: Interventional

Funder types: Other

Identifiers

NCT03827447

PRO00033844

Details and patient eligibility

About

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.

Full 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.

Enrollment: 7 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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7 participants in 2 patient groups, including a placebo group

Drug: Vancomycin Group

Active Comparator group

Description:

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

Treatment:

Drug: Vancomycin Oral Capsule

Drug: Placebo Group

Placebo Comparator group

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

Treatment:

Drug: Placebo Oral Capsule