Efficacy of Metronidazole Prophylaxis Against Clostridium Difficile-Associated Diarrhea in High Risk Adult Patients

Study Overview
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Brief Summary
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The purpose of this study is to test if metronidazole prophylaxis is effective in decreasing the incidence of hospital induced Clostridium Difficile diarrhea among patients at high risk for this infection.

Detailed Description
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Clostridium Difficile infection or C. Diff (CDI) is an infection that causes severe diarrhea. Risk factors for this infection include hospitalization, the use of antibiotics, along with medications that decrease the acid in the stomach. This infection leads to a disease which is difficult to treat and can cause serious complications including death in rare cases. This infection also increases medical costs by prolonging hospital stays. Metronidazole (known by the brand name Flagyl) is an antibiotic that has been available for decades and has been used to treat this disease. Flagyl is approved by the Food and Drug Administration for the treatment of C. diff infection. Recent research by the investigators group has shown that hospitalized patients who took Flagyl had a decreased chance of getting C. Diff infection. However, high quality studies are needed to better evaluate whether the investigators can prevent C. Diff infection in high risk patients with the use of Flagyl. The purpose of this study is to assess if metronidazole prophylaxis is effective in decreasing the incidence of hospital induced Clostridium Difficile diarrhea among inpatients at high risk for this infection. High risk patient population are as defined below: taking a broad spectrum antibiotics (piperacillin/tazobactam-Zosyn; Ciprofloxacin).

Official Title
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Efficacy of Metronidazole Prophylaxis Against Clostridium Difficile-Associated Diarrhea in High Risk Adult Patients: A Randomized Clinical Trial

Conditions
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Clostridium Difficile Diarrhea

Intervention / Treatment
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* Drug: Metronidazole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inpatients >55 Proton Pump inhibitor / Histamine-2 Blocker On broad spectrum antibiotics (Zosyn and/or Ciprofloxacin). These two antibiotics are selected based on current hospital formulary/use Anticipated hospital stay >48 hours Mental capacity (able to give informed written consent). Exclusion Criteria: Admission for CDI Existing diarrhea at admission Passed prophylactic window (>48 hours on broad spectrum antibiotics) Unable to take PO at the time of evaluation for study entry No more than 14 days of broad spectrum antibiotics anticipated Medications with serious interactions/contraindications to that would be taken together with metronidazole (ex. Warfarin, disulfiram, phenytoin, calcineurin inhibitors) Inflammatory Bowel Disease Admission for colonic bowel surgery or h/o total/Subtotal colectomy) Hospice Mortality expected <7days Previous CDI in the past 6 months Intensive care admission due to the difficulty of monitoring them Allergy to Metronidazole or other Antibiotics in protocol Patients with neuropathy History of heavy ethyl alcohol intake(greater than 3 drinks daily) or intake in past 24 hours,Solid organ transplant.

Ages Eligible for Study
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Minimum Age: 55 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metronidazole<br>Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days | Drug: Metronidazole<br>* Metronidazole tablets 500mg orally or IV , 3 times a day for a maximum of 14 days<br>* Other names: Flagyl;|
| Placebo Comparator: Placebo<br>Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days | Drug: Placebo<br>* Placebo(Corn starch pill) orally 3 times a day for a maximum of 14 days<br>* Other names: corn starch pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Clostridium Difficile Diarrhea in Both Study Groups at 30 Days Post Broad Spectrum Antibiotic Use. |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Differences in Clostridium Difficile Diarrhea Incidence Between Patients on Piperacillin/Tazobactam vs. Patients on Ciprofloxacin. |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diarrhea, Clostridium difficile infection, Flagyl, Metronidazole