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

• ClinicalTrials.gov Identifier: NCT02200328
• Recruitment Status: Terminated
• First Posted: July 25, 2014
• Results First Posted: June 10, 2016
• Last Update Posted: May 17, 2017
• Sponsor: Alison Schneider
• Information provided by (Responsible Party): Alison Schneider, Cleveland Clinic Florida

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Clostridium Difficile Diarrhea	Drug: Metronidazole; Drug: Placebo	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 76 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Care Provider)
• Primary Purpose: Prevention
• Official Title: Efficacy of Metronidazole Prophylaxis Against Clostridium Difficile-Associated Diarrhea in High Risk Adult Patients: A Randomized Clinical Trial
• Study Start Date: August 2014
• Actual Primary Completion Date: March 2016
• Actual Study Completion Date: March 2016

Arms and Interventions

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 Name: 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 Name: corn starch pill

Outcome Measures

Primary Outcome Measures :

1. The Incidence of Clostridium Difficile Diarrhea in Both Study Groups at 30 Days Post Broad Spectrum Antibiotic Use. [ Time Frame: 30 days ]

Secondary Outcome Measures :

1. Determine Differences in Clostridium Difficile Diarrhea Incidence Between Patients on Piperacillin/Tazobactam vs. Patients on Ciprofloxacin. [ Time Frame: 30 days ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Cleveland Clinic Florida

Weston, Florida, United States, 33331

Sponsors and Collaborators

Alison Schneider

Investigators

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

More Information

• Responsible Party: Alison Schneider, M.D, Cleveland Clinic Florida
• ClinicalTrials.gov Identifier: NCT02200328
• Other Study ID Numbers: FLA14-061
• First Posted: July 25, 2014
• Results First Posted: June 10, 2016
• Last Update Posted: May 17, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Alison Schneider, Cleveland Clinic Florida:

Clostridium difficile infection; Diarrhea; Flagyl; Metronidazole

Additional relevant MeSH terms:

Clostridium Infections; Diarrhea; Signs and Symptoms, Digestive; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Metronidazole; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents