- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02817165
Probiotics for the Prevention of Antibiotic-Associated Diarrhea (PAID)
Probiotics in the Prevention of Antibiotic-Associated Diarrhea in Hospitalized Children: a Randomized Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Ontario
-
Hamilton, Ontario, Canada, L8N 3Z5
- McMaster Children's Hospital
-
Toronto, Ontario, Canada, M5G 1X8
- The Hospital for Sick Children
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Participants will be children aged 1 year to 17 years admitted to the General Pediatric inpatient unit at The Hospital for Sick Children (Site 1) or McMaster Children's Hospital (Site 2).
- Participants will be prescribed IV antibiotics with a planned duration of 1 or more days, and a total course of both IV and oral antibiotics, if applicable, of no more than 28 days.
- Parent (if parent-report) or patient (if patient-report) is able to communicate in English (read, write, speak).
Exclusion Criteria:
- Parental or patient (e.g. child > 12 years old) report of current diarrhea, diarrhea within the last week.
- Lactose intolerance.
- Allergies to strawberry, dried citrus pulp, or any other components of the study product.
- Immuno-compromised patients or those on immunosuppressive agents (e.g. heart or kidney transplant, complex care, sickle cell disease, chemotherapy agents, oral prednisone).
- Patients with known or potentially compromised gut integrity (e.g. short gut, Inflammatory Bowel Disease, Celiac disease, Irritable Bowel Syndrome, nasogastric, nasojejunal or gastrostomy tube).
- Children with serious and/or unstable medical conditions (e.g. diabetes, cardiovascular, renal, lung, psychiatric illness, bleeding disorders, etc.).
- Children admitted to a medical or surgical subspecialty unit.
- Patients enrolled in another study.
- Patients previously randomized to this study.
- Patient is pregnant.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Probiotic (BioK+)
Children will receive 10-40 billion CFUs/day of Bio-K+ (Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2), with dose based on their weight.
The product will be administered as a strawberry flavored tub of milk.
|
Probiotic (BioK+) with 3 stains of Lactobacillus
|
Placebo Comparator: Placebo
Strawberry flavored tub of milk, identical (taste, color, odor) to the active Bio-K+ treatment.
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Strawberry flavored tub of milk, identical (taste, color, odor) to the active Bio-K+ treatment.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of antibiotic-associated diarrhea (AAD)
Time Frame: 2 weeks after antibiotic + probiotic completion
|
The investigators will employ a questionnaire addressing Pediatric Acute Diarrhea (qPAD), a measure of diarrhea involving the assessment of stool frequency and consistency for each bowel movement.
To measure consistency, the qPAD contains a stool consistency classification system.
Our registered sample size is based on pilot data from The Hospital for Sick Children indicating that the incidence of AAD is 33% (95% CI 23% to 43%) according to the qPAD.
Given an estimated baseline AAD risk of 32.9% and a 48% relative risk reduction in AAD (Johnston et al, Cochrane Library, 2011), a randomized trial with 80% power and a 2-sided alpha of 0.05 comparing Bio-K+ with placebo would require a total sample size of 118 patients per group (236 total).
|
2 weeks after antibiotic + probiotic completion
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Incidence of antibiotic-associated diarrhea (AAD), global impression
Time Frame: 2 weeks after antibiotic + probiotic completion
|
Given that parents have knowledge of the child's typical bowel movements per day, the investigators will also employ a Global Rating Scale for diarrhea (GRSd), using a 0 to 4 scale (0 = no diarrhea, 1 = mild diarrhea, 2 = moderate diarrhea, 3 = severe diarrhea, 4 = worse imaginable diarrhea).
The investigators will ask participants to select values based on diarrhea severity, which is a combination of stool frequency and consistency over 24 hours.
Our registered sample size is based on the incidence of AAD (33%; 95% CI 23% to 43%) according to the qPAD.
However, the incidence of AAD according to GRSd is 23%, which corresponds to the lower bound of the 95% CI for the qPAD.
The investigators are currently applying for additional peer-reviewed funds.
If these funds are obtained the investigators will power the trial based GRSd, a more conservative AAD incidence (23%).
The investigators will also power the trial for a smaller treatment effect (39% relative risk reduction).
|
2 weeks after antibiotic + probiotic completion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Severity of AAD
Time Frame: 2 weeks after antibiotic completion
|
The investigators will assess severity using the qPAD and the investigators will employ definitions for diarrhea from the Canadian Nosocomial Infection Surveillance Program, modified for use in children, defined as: severe: ≥6 loose/unformed/liquid stools; moderate: ≥3 loose/unformed/liquid stools; mild: a change in stooling pattern to 1-2 loose/unformed/liquid stools daily (Gravel 2007).
The investigators will classify severity according to the 24-hour period with the highest degree of severity.
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2 weeks after antibiotic completion
|
Adverse events
Time Frame: 2 weeks after antibiotic completion
|
Incidence of mild (e.g.
self-resolving), moderate (e.g.
those that warrant medical evaluation) and serious (e.g.
those that warrant continued hospitalization) adverse events based on criteria adopted by the National Institute of Health common terminology criteria for adverse events (NIH severity) will be evaluated.
|
2 weeks after antibiotic completion
|
Duration of AAD
Time Frame: 2 weeks after antibiotic completion
|
The investigators will measure duration of AAD using a definition of diarrhea resolution (diarrhea offset) developed based on a systematic review of 138 trials of Pediatric Acute Diarrhea, and Delphi consensus with a panel of experts in pediatrics, clinical gastroenterology and measurement (Johnston BC et al. Pediatrics 2010; Jul;126(1):e222-31; Johnston BC et al. Symposium Probio, Quebec City, Canada, 2015). For children up to 17 years of age, acute diarrhea typically lasts less than 7 days and not longer than 14 days and resolution is marked by
|
2 weeks after antibiotic completion
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Gordon Guyatt, MD, McMaster University
Publications and helpful links
General Publications
- Goldenberg JZ, Lytvyn L, Steurich J, Parkin P, Mahant S, Johnston BC. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev. 2015 Dec 22;(12):CD004827. doi: 10.1002/14651858.CD004827.pub4.
- Johnston BC, Shamseer L, da Costa BR, Tsuyuki RT, Vohra S. Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review. Pediatrics. 2010 Jul;126(1):e222-31. doi: 10.1542/peds.2009-3667. Epub 2010 Jun 21.
- Johnston B, Pirrello D, Lytvyn L, Mahant S, Sherman P, Ship N, Parkin P. Prospective cohort study of antibiotic-associated diarrhea among hospitalized children. Symposium Probio, Quebec City, Canada. (October 29, 2015).
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1000052303
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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