Use of Bismuth Subsalicylate in Clostridium Difficile Colitis

Can Use of Bismuth Subsalicylate in Clostridium Difficile Patients Decrease the Length of Stay and Time to Resolution of Symptoms

Clostridium difficle infection is the leading cause of hospital acquired infection and infectious diarrhea in hospitalized patients. Eradication treatment for this infection is the challenging tasks for clinicians due to treatment resistance developed from new hypervirulent strains. The recurrence rate of this infection is around 20% and there is high likelihood(60-70%) of another episode after index recurrence. Given constant challenge new treatment options are under study. Aim of the study is to evaluate if use of bismuth subsalicylate (BSS) can decrease the length of stay in patients admitted with Clostridium difficile infection. Secondarily investigators will also see if there is any impact of BSS in decrease the recurrence.

Study Overview

• Status: Withdrawn
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Drug: standard antibiotic therapy; Drug: Bismuth Subsalicylate

Detailed Description

Clostridium difficile (C.Diff) infection is the leading cause of hospital acquired infection and infectious diarrhea in hospitalized patients. Eradication treatment for this infection is the challenging task for clinicians due to treatment resistance developed from new hypervirulent strains. The recurrence rate of this infection is around 20% and there is high likelihood (60-70%) of another episode after index recurrence. Given constant challenges new treatment options are under study.

The purpose of this study is to examine if the addition of bismuth subsalicylate (BSS) (the active ingredient in Pepto-Bismol) 524 mg ((2) 262 mg tablets) given four times per day for 14 days to standard of care treatment of C.Diff will decrease the length of stay and decrease the time to resolution of C.Diff symptoms compared to patients who received standard of care treatment for C.Diff alone.

Bismuth subsalicylate has been used for long time in infectious diarrhea and is over the counter drug with few side effects. Studies in hamsters have shown bismuth subsalicylate to be effective in treating C.Diff. Investigators believe given cheaper cost and less side effect profile this drug is worth looking for treatment of C.Diff infection which has a huge burden on health care.

This is an open label, randomized, controlled trial. Hospitalized patients aged 18 years or older with positive stool test for C.Diff toxin will be randomized to one of two treatment groups:

Group 1 will receive standard of care treatment for C.Diff alone Group 2 will receive BSS 524 mg four times daily for 14 days along with standard of care treatment Oral antibiotic therapy will be limited to oral vancomycin 125 mg every 6 hours daily which is the standard dose for the treatment of clostridium difficile.

Length of stay and time to resolution of symptoms will be measured and compared between the two treatment groups as primary outcomes. Resolution of symptoms is defined has having < 3 diarrheal episodes in 24 hours. The study will also record episodes of recurrence, defined as the reappearance of symptoms within 8 weeks of the completion of antibiotic treatment and the resolution of initial symptoms. Recurrence rates will be compared between the two treatment groups as a secondary outcome.

Both Groups 1 & 2 will have 2 week and 8 week follow up phone calls. Group 1 participants will be called 2 weeks after consent/enrollment in the study to verify antibiotic therapy is completed, verify when/if CDiff symptoms resolved, collect data about any adverse events. Group 2 participants will be called 2 weeks after the initiation of study drug (which should be < 24 hours after consent). The visit window will start on the day the participant is scheduled to complete study drug. The purpose of the call will be to verify that both antibiotics and study drug have been completed, verify when/if CDiff symptoms resolved, and collect data about any adverse events.

Both Groups 1 and 2 participants will be called 8 weeks after the expected (or known) completion date of antibiotic therapy prescribed for the treatment of CDiff to see if CDiff symptoms have recurred and if there have been any adverse events..

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Cooperstown, New York, United States, 13326
      • Bassett Healthcare Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 or older
• Hospitalized patient with documented positive stool test for CDiff
• Able and willing to provide informed consent

Exclusion Criteria:

• Pregnancy
• Breastfeeding
• Known allergy to BSS or other salicylates, including aspirin
• History of bleeding disorder
• History of gastrointestinal bleed,
• History of gastrointestinal ulcer
• Chronic use of anticoagulants
• Chronic NSAID use

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard care alone; Participants will receive standard antibiotic therapy for Clostridium Difficile (CDiff) infection without additional adjuvant therapy.	Drug: standard antibiotic therapy; antibiotic therapy administered per standard protocol
Experimental: Standard care with Bismuth subsalicylate (BSS); Participants will receive BSS524 mg ((2) 262 mg tablets) four times per day for 14 days in addition to standard antibiotic therapy.	Drug: Bismuth Subsalicylate; BSS 524 mg ((2) 262 mg tablets) given four times per day for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay	number of days hospitalized after the initiation of treatment for CDiff	70 days (study period = 14 days of antibiotic treatment plus 8 weeks/56 days post treament completion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to resolution of symptoms	Resolution of symptoms is defined as having < 3 diarrheal episodes in 24 hours	70 days
CDiff Recurrence	Recurrence is defined as the reappearance of symptoms within 8 weeks of the completion of antibiotic treatment and the resolution of initial symptoms	70 days

Collaborators and Investigators

• Sponsor: Bassett Healthcare
• Investigators: Principal Investigator: Abdulhadi Quadri, MD, Bassett Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2018
• Primary Completion (Actual): July 1, 2018
• Study Completion (Actual): July 1, 2018

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (Actual): July 19, 2018

Study Record Updates

• Last Update Posted (Actual): July 19, 2018
• Last Update Submitted That Met QC Criteria: July 9, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Clostridium Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Gastrointestinal Agents; Antacids; Antidiarrheals; Anti-Bacterial Agents; Bismuth; Bismuth subsalicylate
• Other Study ID Numbers: 2089

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No