Optimal Treatment for Recurrent Clostridium Difficile

  • STATUS
    Recruiting
  • End date
    May 31, 2022
  • participants needed
    549
  • sponsor
    VA Office of Research and Development
Updated on 13 October 2021

Summary

The purpose of this study is to determine whether fidaxomicin and vancomycin followed by taper and pulse vancomycin treatment are superior to standard vancomycin treatment for the treatment of recurrent Clostridium difficile infection.

Description

Abstract Clostridium difficile is the most common cause of healthcare-associated infectious diarrhea among adults in industrialized countries. In addition to diarrhea, C. difficile infection (CDI) may also result in serious complications such as shock, toxic megacolon, colectomy, and death. The Centers for Disease Control and Prevention (CDC) has estimated C. difficile results in 250,000 hospital infections, 14,000 deaths, and $1 billion in excess costs annually. Recurrent CDI is the most challenging clinical dilemma facing clinicians who treat this disease. An estimated 30% of patients who respond to initial treatment with either vancomycin or metronidazole develop recurrent CDI, usually within 1-4 weeks of completing treatment.

The primary objective of this study is to determine whether 1) standard fidaxomicin treatment and 2) standard vancomycin treatment followed by taper and pulse vancomycin treatment are superior to standard vancomycin treatment alone for sustained clinical response at day 59 for all treatments, for participants with either their first or second recurrence of CDI. Veterans presenting with a first or second CDI recurrence will be screened, consented and randomly assigned in a double-blind manner equally to one of three treatment groups: 1) a 10 day course of oral vancomycin (VAN-TX), 2) a 10 day course of fidaxomicin (FID-TX) or 3) a 31 day course of vancomycin which includes a taper and pulse following daily treatment (VAN-TP/P). Symptom resolution is defined as an improvement or resolution of diarrhea ( 3 unformed bowel movements over 24 hours) for 48 consecutive hours compared to the participant's baseline. Recurrence is defined as having diarrhea (>3 loose or semi-formed stools over 24 hours for 48 consecutive hours). A sample size of 549 randomized study participants is required to obtain 91% global power to detect a 16% absolute difference (expected proportion of 31% in the VAN-TX group) in sustained clinical response (D- COM) proportion for at least one comparison (VAN-TP/P vs. VAN-TX, FID-TX vs. VAN-TX) at the family wised error rate (FWER) 0.05 level. The marginal probability (disjunctive power) of detecting 16% absolute difference for each comparison is 81%. The expected withdrawal rate prior to day 59 (prior outcome assessment) is estimated to be 10%. If both FID-TX and VAN-TP/P are found to be superior to VAN-TX, then the non-inferiority of VAN-TP/P to FID-TX will be assessed.

With the assumption that sites recruit 6 participants (site average) per year for sites primarily recruiting from the main hospital and nearby CBOCS, and 9 participants (site average) per year for sites that could partner with independent VAMCs (Independent VAMCs LSI Application will be reviewed and approved by Central IRB) that are close in distance to allow a shared site coordinator (WOC appointed) at an increased funding level, the study is expected to complete enrollment of 549 participants within 6 years with 90 days of follow-up. This includes 2 years of pilot phase plus transitioning period from pilot phase to full study, and 4 years of full study. There were 6 sites in the pilot phase and will have 24 units (26 sites) in full phase (including 5 pilot sites and 21 additional sites). Sites that are significantly below the recruitment target for an extensive period may be considered for termination. The recruitment timeline and the number of sites will be re-evaluated based on the actual recruitment rate, the number of sites still recruiting, whether replacement or additional sites will be added, the study time period on administrative recruitment hold due to COVID-19 pandemic, and available funding resources.

Details
Condition Vancomycin, Clostridium, Difficile, Fidaxomicin, vanco
Treatment Vancomycin, Fidaxomicin, Vancomycin with Taper/Pulse
Clinical Study IdentifierNCT02667418
SponsorVA Office of Research and Development
Last Modified on13 October 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Informed consent obtained and signed
Age > 18
If female, participant must not be pregnant or nursing
Negative pregnancy test required for females <61 years of age or without prior hysterectomy
Confirmed current diagnosis of CDI, determined by having
>3 loose or semi-formed stools for participants over 24 hours AND
Positive stool assay for C. difficile
EIA positive for toxin A/B; or
Cytotoxin assay; or
Nucleic Acid Amplification Test (NAAT, PCR or LAMP) based detection of toxigenic C. difficile
Current episode represents the first recurrent episode of CDI within 3 months of the primary CDI episode in a patient who has not had CDI in the 3 months prior to the primary episode OR a second recurrent CDI episode occurring within 3 months of the first recurrent episode, as defined above
At least one of the previous CDI episodes must have been confirmed by a stool assay for C. difficile

Exclusion Criteria

Inability to provide informed consent
Inability to take oral capsules
Receipt of >72 hours of antibiotics considered effective in the treatment of CDI
including
metronidazole
vancomycin
fidaxomicin
nitazoxanide
rifaximin
Prior infusion of bezlotoxumab within the previous 6 months
Known presence of fulminant CDI, including hypotension, severe ileus or GI obstruction or incipient toxic megacolon
Receipt of more than a single course of oral vancomycin, fidaxomicin, or a vancomycin tapering regimen since the primary episode of CDI as defined above
Known allergy to vancomycin or fidaxomicin
Acute or chronic diarrhea due to inflammatory bowel disease or other cause (e.g., presence of an ileostomy or colostomy) that would confound evaluation of response to CDI treatment
Anticipation of need for long term systemic antibiotic treatment (beyond 7 days)
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note