Probiotics for the Prevention of Antibiotic-Associated Diarrhea

NCT02817165 | Terminated DMC

• 1 other identifier: 1000052303
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

In North America, one of the most common reasons for hospitalization in previously healthy children is for the treatment of infections with antibiotics. This study will determine if, in previously healthy children hospitalized and prescribed intravenous (IV) antibiotics, the co-administration of a probiotic milk product containing good bacteria, is safe and effective for reducing AAD, as compared to a placebo (identical appearing milk product). This will be a two-center, randomized, masked, placebo-controlled clinical trial. The results of this study will help inform clinicians and families on the use of probiotics in the prevention of AAD, a common side effect of antibiotic use among hospitalized children.

Conditions

Acute Diarrhea

Keywords

Probiotics, diarrhea, antibiotic, children, hospital

Outcome Measures

Primary Outcomes (2)

• Incidence of antibiotic-associated diarrhea (AAD)

  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

• Incidence of antibiotic-associated diarrhea (AAD), global impression

  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 Outcomes (3)

• Severity of AAD

  2 weeks after antibiotic completion

• Adverse events

  2 weeks after antibiotic completion

• Duration of AAD

  2 weeks after antibiotic completion

Study Arms (2)

Probiotic (BioK+)

EXPERIMENTAL

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.

Dietary Supplement: Probiotic (BioK+)

Placebo

PLACEBO COMPARATOR

Strawberry flavored tub of milk, identical (taste, color, odor) to the active Bio-K+ treatment.

Other: Placebo

Interventions

Probiotic (BioK+) DIETARY_SUPPLEMENT

Probiotic (BioK+) with 3 stains of Lactobacillus

Probiotic (BioK+)

Placebo OTHER

Strawberry flavored tub of milk, identical (taste, color, odor) to the active Bio-K+ treatment.

Placebo

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• McMaster University: collaborator

Study Sites (2)

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (3)

• 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.

  PMID: 20566617 BACKGROUND

• 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).

  BACKGROUND

• 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.

  PMID: 26695080 BACKGROUND

MeSH Terms

Conditions

Diarrhea

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Patricia Parkin, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

• Gordon Guyatt, MD

  McMaster University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Director, Senior Associate Scientist and Professor

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: June 29, 2016
• Study Start: November 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: January 1, 2018
• Last Updated: April 18, 2018

Record last verified: 2018-04

Locations

CA (2)