Initial Vancomycin Taper for the Prevention of Recurrent Clostridium Difficile Infection (TAPER-V)

  • STATUS
    Recruiting
  • End date
    Mar 19, 2024
  • participants needed
    552
  • sponsor
    McGill University Health Centre/Research Institute of the McGill University Health Centre
Updated on 19 April 2022
Investigator
Jennifer Eastmond
Primary Contact
Jewish General Hospital (8.4 mi away) Contact
+2 other location

Summary

The first line therapy for an initial episode of CDI (Clostridium difficile infection) is 10-14 days of oral vancomycin which is now recommended over metronidazole in the 2018 guidelines from the Association of Medical Microbiologists and Infectious Diseases of Canada (AMMI). Although response rates for the treatment of a first episode of CDI now approach 90%, approximately 25% of patients who have a complete response will develop recurrence (rCDI) within 8 weeks. Doctors' ability to predict recurrence is evolving, but remains very limited.

The investigators hypothesize that by extending initial vancomycin therapy with a 2-week tapering regimen this will reduce the risk of rCDI. Starting at the end of the initial 14 days of therapy, participants will be randomized to receive an additional 14-days of placebo or vancomycin taper (125 mg orally twice daily x 7 days followed by 125 mg orally once daily x 7 days). This taper was chosen as it represents two steps of a commonly used 4-week vancomycin taper.

The investigators' proposal to evaluate the extension of initial treatment from 14 to 28 days with a tapering dose of vancomycin represents a practical clinical trial that capitalizes on oral vancomycin's safety profile, worldwide availability, and relatively low cost.

Description

STUDY POPULATION

This is a multi-centre study involving institutions in British Columbia, Ontario and Quebec. The study population will be drawn from patients cared for as inpatients or outpatients at the participating hospitals. Such patients will have a test positive for Clostridium difficile and will be receiving treatment. The trial will involve only adult patients 18 years of age and older.

Criteria for Recruitment

The microbiology laboratory will notify the study team about a positive CDI test via telephone, email, or fax. The nature of recruitment will then depend on the inpatient status of the patient at the time of the test.

Inpatients

Pre-existing approval for approaching patients for this study will be obtained from the relevant department heads. The study team will speak with a member of the inpatient treating team (resident physician or faculty physician as appropriate) to determine if the patient is appropriate for recruitment. If this seems to be the case, the patient's file will be rapidly screened to determine eligibility and if the patient is eligible they will be approached for consent.

Outpatients

The physician who ordered the C. difficile test will be contracted to determine if the patient is appropriate for recruitment. At the invitation of this physician, the investigators will then contact the patient via telephone to evaluate suitability for inclusion and arrange an intake visit.

RANDOMIZATION

For patients who have enrolled in the study, randomization will occur centrally at McGill via an existing internet application (such as https://cloudtrials.mchi.mcgill.ca/) and will be performed by permuted block with randomized block sizes. This randomization will be stratified for first episode or first recurrence at study entry to ensure these factors are properly balanced.

TRIAL SCHEDULE

  • Day 1: Patient diagnosed with C. difficile -> Determine eligibility and obtain permission for approach
  • Day 7-10 (Patient's C. difficile has improved and meets eligibility): Consent obtained; randomization; distribution of study drug for day 14 start -> Collection of demographics, storage of stool.
  • Day 14-28 -> Receipt of study therapy
  • Day 28: In person visit
  • Day 56: In person visit -> Primary outcome determined, quality of life questionnaire
  • Day 90: Study ends for the patient -> Secondary outcomes can be determined
  • weekly until Day 56: Brief questionnaire -> By email/text/phone
  • biweekly after Day 56: Brief questionnaire -> By email/text/phone
  • Ad hoc: If patient has symptoms of recurrence of C. difficile -> Review by ID physician in clinic if possible, otherwise usual doctors or emergency room

Patients will be able to come be assessed for potential relapse by infectious diseases physicians at each site (who may or may not be a part of the study) or could see their usual doctors.

SAMPLE SIZE AND STATISTICAL METHODS

The estimated number of CDI cases available has been based on fiscal year 2016 data: total of 1770 per year.

The risk of recurrence is estimated at 25%. The investigators aim to demonstrate that an initial tapering regimen is associated with an absolute decrease in the risk of relapse of at least 10% (number needed to treat of 10) which would be similar to than the effect seen within 40 days in the fidaxomicin trial. This estimate accounts for our longer period of follow up and will allow some flexibility in the actual recurrence rate found in our control arm. With 80% power and a type 1 error of 5%, this would require 276 patients to complete follow up in each arm (total 552).

Details
Condition Clostridium Difficile Infection
Treatment placebos, Vancomycin
Clinical Study IdentifierNCT04138706
SponsorMcGill University Health Centre/Research Institute of the McGill University Health Centre
Last Modified on19 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

All consecutive adult patients (inpatients and outpatients) who have a treated first episode or first recurrence of CDI
CDI will be defined by a positive PCR for toxin gene and/or detection of toxin by EIA or CCA along with three or more episodes of diarrhea within 24 hours
Patients with a positive test with less than three bowel movements may be included if they initially presented with ileus or if they had pseudomembranous colitis visualized on colonoscopy

Exclusion Criteria

Clinical
Toxic megacolon at presentation not resolved by day 10
For the current episode of CDI: use of fidaxomicin, fecal microbiota transplant or intravenous immunoglobulins
Previous or current colectomy
Severe allergy/intolerance to oral vancomycin
Patient is expected to die within 3 months from another disease or is expected to be admitted to a palliative care unit
Failure to achieve clinical cure (as above) by day 10
More than 2 lifetime episodes of C. difficile
Documented history of sensorineural hearing loss (other than presbycusis and noise induced hearing loss). The following patients with documented previous subtypes of sensorineural hearing loss will be excluded from the trial: Menière's disease, multiple sclerosis affecting auditory nerves, otic syphilis, viral cochleitis, autoimmune disorders, previous drug induced hearing loss, and otherwise unexplained sudden sensorineural hearing loss (SSNHL)
Administrative
Expected transfer to a palliative care unit or non-study hospital
Known pregnancy or planning to become pregnant during the study period
No provincial health insurance
Women who are breast feeding
Previously enrolled
No reliable means of outpatient contact
Incompetent without healthcare proxy
Patient stated inability to come to follow up appointments
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