Lactobacillus Reuteri in the Prevention of Antibiotic Associated-diarrhea and Clostridium Difficile

Efficacy and Safety of the Probiotic Lactobacillus Reuteri in the Prevention of Antibiotic Associated-diarrhea and Clostridium Difficile Related Infections in Hospitalized Adult Patients

The purpose of this study is to find whether Lactobacillus reuteri prevents antibiotic-associated diarrhea and related Clostridium difficile infections. Subjects will be admitted from the University Hospitals Case Medical Center. They will be randomly assigned to an intervention group receiving L. reuteri or a placebo. Supplementation will occur during antibiotic treatment and for an additional 7 days after cessation of treatment. Data collection will occur at baseline, end of antibiotic use, 7 days after antibiotic cessation, and 21 days after antibiotic cessation. Primary data includes diarrhea instances. Secondary data includes severity of diarrhea, presence of C. difficile toxins, and presence of other GI symptoms.

Study Overview

• Status: Completed
• Conditions: Antibiotic-associated Diarrhea; Clostridium Difficile
• Intervention / Treatment: Dietary supplement: Lactobacillus reuteri

Detailed Description

The data being measured for this study include:

Primary outcome = incidence of diarrhea during and after treatment with antibiotics. An episode of diarrhea is defined as the discrete period between the time when stool output meets or exceeds three soft and unformed or watery bowel movements to the time when formed stools return, which must be at least 48 hours later.

Secondary variables:

1. severity of diarrhea measured as the discrete period between the time when stool output meets or exceeds 3 soft and unformed or watery bowel movements to the time when formed stools return.
2. frequency of stool samples positive for C. Difficile toxin A or B at baseline, when presenting with diarrhea during the study period, and at the follow-up 21 days post-antibiotic-treatment to detect possible clearance of C. Difficile, in patients ingesting L. reuteri versus placebo.
3. frequencies of other gastrointestinal symptoms at 1, 2, and 4 weeks, in the L. reuteri group versus placebo and assessed by the validated Gastrointestinal Symptom Rating Score.

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Receiving antibiotics for not more than 48 hours prior to enrollment and free from diarrhea
• able to understand and sign informed consent and HIPPA
• available throughout the study period
• subjects should have the mental ability to understand and willingness to fulfill all the details of the protocol

Exclusion Criteria:

• three or more soft and unformed or watery stools per day at admission
• receiving chemotherapy or radiation therapy
• diagnosis of inflammatory bowel disease
• NPO without PO meds
• neutropenia (an absolute neutrophil count (ANC) of less than 1500/microL)
• HIV positive with a CD4+ T-lymphocyte count <400 per mcL blood
• requiring care in an intensive care unit
• status-post bowel resection during hospitalization
• patient's receiving antibiotics four weeks prior to hospitalization
• patient with severe life threatening illness or immunocompromised
• pregnancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Identical Placebo	Dietary supplement: Lactobacillus reuteri; One chewable tablet of 1E8 CFU L. reuteri, once per day; Other Names: BioGaia, Probiotic Chewable Tablets
Experimental: L. reuteri	Dietary supplement: Lactobacillus reuteri; One chewable tablet of 1E8 CFU L. reuteri, once per day; Other Names: BioGaia, Probiotic Chewable Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diarrhea	Instances of diarrhea	28+ days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of diarrhea	measured as the discrete period between the time when stool output meets or exceeds three soft and unformed or watery bowel movements to the time when formed stools return.	28+ days
Frequency of stool samples positive for C. difficile toxin A and B	Frequency of stool samples positive for C. difficile toxin A and B at baseline, when presenting with diarrhea during the study period, and at the follow-up 21 days post antibiotic-treatment to detect possible clearance of C. difficile, in patients ingesting L. reuteri versus placebo.	baseline, when presenting with diarrhea during the study period, and at the follow-up 21 days
Frequencies of other gastrointestinal symptoms	Frequencies of other gastrointestinal symptoms at 1, 2 and 4 weeks, in the L. reuteri group versus placebo and assessed by the validated GSRS score (Gastrointestinal Symptom Rating Score).	1, 2 and 4 weeks

Collaborators and Investigators

• Sponsor: Case Western Reserve University
• Collaborators: BioGaia AB
• Investigators: Principal Investigator: Alison L Steiber, PhD, RD, LD, Case Western Reserve University

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: June 23, 2010
• First Submitted That Met QC Criteria: April 28, 2014
• First Posted (Estimate): May 1, 2014

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: induced diarrhea; Clostridium difficile toxicity
• Additional Relevant MeSH Terms: Infections; Signs and Symptoms, Digestive; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Diarrhea; Clostridium Infections
• Other Study ID Numbers: RES504803