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

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

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.

Study Overview

• Status: Terminated
• Conditions: Clostridium Difficile Diarrhea
• Intervention / Treatment: Drug: Metronidazole; Drug: Placebo

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Alison Schneider
• Investigators: Principal Investigator: Alison Schneider, M.D., Cleveland Clinic Florida

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: July 21, 2014
• First Submitted That Met QC Criteria: July 23, 2014
• First Posted (Estimate): July 25, 2014

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: April 17, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Diarrhea; Metronidazole; Clostridium difficile infection; Flagyl
• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole
• Other Study ID Numbers: FLA14-061

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No