Oral Vancomycin for Secondary Prophylaxis of Clostridium Difficile Infection (CDI)

Study Overview
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Brief Summary
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The purpose of this study is to gain further knowledge regarding the effectiveness of vancomycin prophylaxis in preventing Clostridium difficile infections in order to guide physicians' practices.

Detailed Description
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Recurrent Clostridium difficile infection (CDI) is associated with significant morbidity, mortality and health care related costs. Up to 30% of CDI cases recur, resulting in 83,000 cases of recurrent CDI per year in the US. Although agents for primary and secondary prophylaxis for CDI including the use of probiotics, antibiotics, fecal microbiota transplantations, and newer therapies such as bezlotoxumab have been reported, there are no consensus guidelines regarding their use. In order to understand current practices regarding secondary prophylaxis for CDI, a nationwide survey to assess physician practices regarding secondary prophylaxis for CDI. A total of 246 surveys were completed. Physicians were surveyed from greater than 100 locations. Most providers (N=173, 71%) reported using secondary prophylaxis for CDI prevention. The majority (N=138, 56%) were infectious disease providers. Vancomycin (N=121, 70%) and probiotics (N=114, 66%) were most commonly used for CDI secondary prophylaxis. Of 164 respondents who used secondary prophylaxis, 29.9% (N=49) utilized it for patients with a history of CDI who were receiving antibiotics, while 54.2% (N=89), used prophylaxis for patients with a history of recurrent CDI (more than 2 episodes) receiving antibiotics. Despite the lack of guideline recommendations or definitive studies to support secondary prophylaxis for CDI, the majority of the physicians who responded to this survey are using secondary prophylaxis to prevent recurrent CDI. The purpose of our study is to determine the effectiveness of secondary prophylaxis with oral vancomycin vs. placebo for the prevention of recurrent clostridium difficile infection.

Official Title
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A Randomized, Double-Blinded Placebo Controlled Study To Determine the Effectiveness of Oral Vancomycin for Secondary Prophylaxis of Clostridium Difficile Infection (CDI)

Conditions
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Clostridium Difficile Infection, Clostridium Difficile Infection Recurrence

Intervention / Treatment
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* Drug: Oral Vancomycin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted to Tampa General Hospital or outpatients at Infectious Disease Associates of Tampa Bay clinics who are receiving systemic antibiotics and have a history of at least one episode of CDI. Participants must at least 18 years of age to participate. Participants must be able to understand and sign a written informed consent form prior to initiation of study procedures. Expected to receive at least 3 days of systemic antibiotics. Life expectancy greater than 6 months. Exclusion Criteria: Current CDI Completion of treatment for CDI within the last 15 days Concurrent use of drugs that have activity against C. difficile such as metronidazole, fidaxomicin, nitazoxanide, tigecycline, or rifaximine Concurrent use of cholestyramine Concurrent use of bezlotoxumab Concurrent use of probiotics Concurrent use of Imodium or other antidiarrheal agents. Chronic suppressive antibiotics Condition which causes chronic diarrhea such as inflammatory bowel disease Bacterial gastroenteritis other than CDI Pregnancy or breastfeeding Allergy to oral Vancomycin Inability to take enteric medications Have an unstable or life limiting condition on admission Already participating in another study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Our primary objective is to determine the effectiveness of vancomycin in preventing recurrent Clostridium Difficile Infection (CDI) compared to placebo. Our secondary objective is to attempt to identify risk factors associated with the development of recurrent CDI. The purpose of this study is to gain further knowledge regarding the effectiveness of vancomycin prophylaxis in preventing Clostridium difficile infections in order to guide physicians' practices. Eligible patient's will be randomized 1:1 double-blinded placebo controlled clinical trial to determine the effectiveness of vancomycin at preventing CDI. The first arm in our study would be the study drug which is oral vancomycin. The second arm would be placebo. Patient with a history of CDI admitted to Tampa General Hospital or have been seen at Infectious Disease Associates of Tampa Bay clinics are receiving systemic antibiotics and have a history of at least one episode of CDI that was diagnosed on or after 4/1/2017.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study drug<br>Oral vancomycin 125mg twice a day prescribed for the duration of antibiotics | Drug: Oral Vancomycin<br>* Oral vancomycin 125mg twice a day prescribed for the duration of antibiotics<br>|
| Placebo Comparator: Placebo<br>Matched placebo twice a day prescribed for the duration of antibiotics | Other: Placebo<br>* Matched placebo twice a day prescribed for the duration of antibiotics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Rate | Diagnosis of Clostridium Difficile infection to assess recurrence rates Participants will be called at the completion of systemic antibiotics and 1, 2 and 3 months thereafter to assess for recurrence. If participants were tested for C. difficile at another facility records will be obtained to confirm recurrent infection. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk factors associated clostridium difficile infection recurrences | Assess any risk factors associated development of recurrence such as age, number of clostridium difficile infections in the past, what antibiotics the patient has been exposed to, and exposure to proton pump inhibitors | Day 0 - data will be collection upon enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prophylaxis