Oral Vancomycin vs Placebo in the Prevention of Recurrence of Clostridioides Difficile's Infection

Study Overview
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Brief Summary
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A phase III randomized clinical trial in proportion 2:1 in favor of oral vancomycin (experimental treatment), multicentric, national, double-blinded, controlled with placebo. The main objective is to evaluate the effectiveness of treatment with oral vancomycin to reduce the incidence of Clostridioides difficile infection (CDI) in patients who suffered previous CDI and who need further hospitalization and treatment with systemic antibiotic therapy in the 90 days after the first CDI.

Detailed Description
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As secondary objectives the investigators intend to: Evaluate the effectiveness of the treatment with oral vancomycin as part of the prophylaxis arsenal to prevent ICD in patients with previous ICD episodes stratified by the number of previous recurrences. Compare the severity of recurrences in both study groups. Compare the effectiveness of the treatment with oral vancomycin depending on the type of systemic antibiotic therapy prescribed. Evaluate the tolerance and the safety of the treatment with oral vancomycin in terms of secondary effects and difficulty in therapeutic compliance. Evaluate if the treatment with oral vancomycin has an effect in diminishing the severity of ICD recurrences.

Official Title
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Phase III,Randomized,Double-blinded Clinical Trial to Evaluate the Effectiveness and Safety of Oral Vancomycin Vs Placebo in the Prevention of Recurrence of C.Difficile Infection in Patients Under Treatment With Systemic Antibiotic Therapy

Conditions
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Clostridioides Difficile Infection

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age equal or superior to 18 years Previous history of Clostridioides difficile infection in the 90 days before the study enrolment Need for hospitalization and need of antibiotic therapy Signature of informed consent Exclusion Criteria: Woman of childbearing age, pregnant woman, or breastfeeding woman Hypersensitivity to vancomycin Inability to comply with study protocol Critically ill condition or life expectancy less than 30 days Patients with diagnosed inflammatory bowel disease or with any conditions that produce chronic diarrhea Fulfilment of the criteria for diarrhea or diagnosis of CDI at the time of assessment for eligibility or in the previous 3 days Therapy with oral vancomycin or any other agent with activity against C. difficile for >48 hours in the previous 3 days;. Prophylaxis with oral vancomycin or any other agent with activity against C. difficile within the 70 days before the assessment for eligibility Systemic antibiotic therapy for 72 hours or more before the recruitment Ongoing enrolment in another RCT evaluating the effectiveness of other drugs Estimated use of systemic antibiotic therapy for more than 4 weeks

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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No

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: Proportion 2:1 in favour to the intervention arm
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>A group of patients will be treated with a blinded capsule that contains 125mg of vancomycin every 6 hours for 10 days. | Drug: Oral Vancomycin<br>* A blinded capsule that contains 125mg of vancomycin every 6 hours during 10 days.<br>|
| Placebo Comparator: Placebo group<br>A group of patients will be treated with a blinded capsule that contains a placebo every 6 hours for 10 days. | Drug: Placebo<br>* A blinded capsule that contains no vancomycin every 6 hours during 10 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of treatment with oral vancomycin in the prevention of Clostridioides difficile | Absolute difference in the rate of C. difficile infection recurrences with vancomycin Vs placebo. | 60 days after the beginning of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of treatment with oral vancomycin according to the number of previous recurrences | The absolute difference in the rate of C. difficile infection recurrences with vancomycin vs placebo stratified by index CDI episode (first episode or recurrence) | 60 days after the beginning of the intervention | 
| Effectiveness of treatment with oral vancomycin in diminishing the severity of the recurrence | The absolute difference in the rate of severe C. difficile infection recurrences with vancomycin vs placebo | 60 days after the beginning of the intervention | 
| Effectiveness of treatment with oral vancomycin depending on antibiotic therapy | The absolute difference in the rate of C. difficile infection recurrences with vancomycin vs placebo stratified by the type of systemic antibiotic therapy prescribed. | 60 days after the beginning of the intervention | 
| Tolerance and safety of treatment with oral vancomycin | Rate of major adverse events and drug-related adverse events. | 60 days after the beginning of the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vancomycin oral capsules