What side effects are associated with this type of intervention?

The most common treatments for Clostridium Difficile Infection (CDI) include vancomycin, fidaxomicin, and metronidazole. Vancomycin is generally well-tolerated but can cause side effects such as nausea, abdominal pain, and, rarely, nephrotoxicity. Fidaxomicin has minimal impact on the gut microbiome but may cause nausea, vomiting, and abdominal pain. Metronidazole, although less commonly used now due to higher failure rates, can cause gastrointestinal upset, a metallic taste, and peripheral neuropathy with prolonged use. Extended vancomycin therapy, which involves a gradual reduction of the dose, aims to reduce recurrence rates but shares similar side effects with standard vancomycin treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for Clostridium difficile infection (CDI). Vancomycin, an oral antibiotic, is commonly used and has been recommended over metronidazole for initial episodes of CDI. Fidaxomicin, another oral antibiotic, has been approved for its minimal impact on the microbiome and lower recurrence rates compared to vancomycin. Bezlotoxumab, a monoclonal antibody, is approved for use alongside standard antibiotic treatments to reduce recurrence. Extended vancomycin therapy, involving a gradual reduction of the vancomycin dose, is being studied to further reduce the risk of recurrent CDI.

What other types of research exist?

Promising novel alternatives to extended vancomycin therapy for CDI include fecal microbiota transplantation (FMT), which has been shown to decrease mortality in severe cases, and the administration of spores of nontoxigenic Clostridium difficile strains, which can prevent recurrent infections. Additionally, probiotics have been studied for their potential to prevent CDI, although more research is needed to confirm their efficacy.

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Antibiotic

Extended Vancomycin Treatment for Clostridium Difficile Infection (TAPER-V Trial)

Phase 3

Waitlist Available

Led By Todd C Lee, MD, MPH

Research Sponsored by McGill University Health Centre/Research Institute of the McGill University Health Centre

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

Failure to achieve clinical cure (as above) by day 10

For the current episode of CDI: use of metronidazole monotherapy*, fidaxomicin, fecal microbiota transplant or intravenous immunoglobulins

Timeline

Screening 3 weeks

Treatment Varies

Follow Up days 15-28 of vancomycin treatment

Awards & highlights

Pivotal Trial

Summary

This trial tests if extending vancomycin treatment with a gradually reduced dose can prevent recurrence of Clostridium difficile infection in adults. The idea is that a longer, gradually reduced antibiotic course will better eliminate the bacteria and lower the risk of the infection coming back. Vancomycin taper regimens are commonly used for the treatment of recurrent Clostridium difficile infections.

Who is the study for?

Adults who've had their first or second bout of Clostridium difficile infection (CDI), confirmed by specific tests, can join. They must have had symptoms like diarrhea but can't have severe allergies to vancomycin, be breastfeeding, or have used certain other treatments for CDI. People with a history of hearing loss from specific causes or serious health issues that might limit their life expectancy are excluded.

What is being tested?

The trial is testing if extending the standard treatment for CDI with a tapering dose of vancomycin helps prevent recurrence. After the usual 14-day course, participants will either continue with a reduced dose of vancomycin for another two weeks or take a placebo instead.

What are the potential side effects?

Vancomycin may cause side effects such as kidney problems, hearing issues, and an imbalance in blood cells leading to infections or bleeding. Allergic reactions are possible but rare.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am an adult being treated for my first or second bout of C. diff infection.

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I have had 3 or more episodes of diarrhea in 24 hours and tested positive for CDI.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My condition did not improve by day 10 of treatment.

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I am currently being treated for CDI with specific medications or procedures.

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I have had part or all of my colon removed.

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My toxic megacolon symptoms have not improved after 10 days.

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I am unable to make my own healthcare decisions and have someone appointed to do so.

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I cannot be reached reliably for follow-up.

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I have had C. difficile more than twice in the past 5 years.

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I cannot attend follow-up appointments.

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I am not expected to live more than 3 months due to another illness.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ days 15-28 of vancomycin treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~days 15-28 of vancomycin treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and days 15-28 of vancomycin treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Central Diabetes Insipidus

Secondary study objectives

C. diff associated quality of life

Discontinuation of study drug

Early recurrence of CDI

+7 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: Intervention: Extended vancomycin regimenActive Control1 Intervention

Following a 14-day initial vancomycin treatment (125mg QID x14 days), the participant will receive active vancomycin for an additional 14 days (125mg twice a day x 7 days, then 125mg once a day for 7 days).

Group II: Control: PlaceboPlacebo Group1 Intervention

Following a 14-day initial vancomycin treatment (125mg QID x14 days), the participant will receive a placebo for an additional 14 days (twice a day x 7 days, then once a day for 7 days).

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Fidaxomicin, vancomycin, and metronidazole are the most common treatments for Clostridium Difficile Infection (CDI). Fidaxomicin works by inhibiting bacterial RNA polymerase, leading to the death of C. difficile with minimal disruption to the normal gut microbiome, which is crucial for preventing recurrence. Vancomycin inhibits cell wall synthesis in bacteria, effectively killing C. difficile but with a higher risk of disrupting the gut microbiome, potentially leading to recurrence. Metronidazole, though less favored due to higher failure rates, works by causing DNA damage in anaerobic bacteria like C. difficile. Extended vancomycin therapy, involving a gradual reduction in dose, aims to reduce recurrence by maintaining therapeutic levels of the drug in the gut for a longer period, thereby ensuring the complete eradication of the infection while allowing the gut microbiome to recover.