Xylitol for the Prevention of Acute Otitis Media Episodes in Children

Study Overview
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Brief Summary
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This is a randomized controlled trial of regular daily use of xylitol (or birch sugar), a natural sweetener that has antimicrobial properties, for the prevention of acute otitis media (AOM, primary outcome) as well as upper respiratory tract infections and dental caries (the two secondary outcomes) in preschool aged children. This trial will be conducted through the TARGet Kids! research network.

Detailed Description
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This is an RCT of regular daily use of xylitol (or birch sugar), a natural sweetener that has antimicrobial properties, for the prevention of acute otitis media (AOM, primary outcome) as well as upper respiratory tract infections and dental caries (the two secondary outcomes) in preschool aged children. Clinical equipoise over the efficacy of xylitol in preventing AOM - a common and costly condition in early childhood - persists even after the completion of three RCTs by a single research group in Finland and one in the United States. Several clinical trials of xylitol for the prevention of dental caries and other studies have demonstrated that the intervention in this trial (3-5 doses of xylitol per day) is safe, well tolerated and feasible for the study period. This trial will be conducted through the TARGet Kids! research network which is undertaking several CIHR funded RCTs and will leverage existing CIHR funded infrastructure and important collaborations. The nominated principal applicant's salary is supported by a CIHR RCT training grant to develop this RCT under the mentorship of a co-principal applicant who is an experienced trialist. This trial has the potential to transform the management of three common conditions during early childhood from treatment to prevention using a currently underutilized antimicrobial substance.

Official Title
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Xylitol for the Prevention of Acute Otitis Media Episodes in Children 2-4: A Pragmatic RCT

Conditions
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Acute Otitis Media, URTI, Dental Caries in Children

Intervention / Treatment
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* Other: Xylitol syrup
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children already enrolled in the TARGet Kids! Network, age 2 - 4 years at start of intervention, parents or care provider able to give consent, able to understand the information in English. Exclusion Criteria: craniofacial malformations, structural middle ear abnormalities, sibling or any other child living at the same address already enrolled in the trial, insertion of ventilation tubes prior to study period, current use of a xylitol product or reported xylitol sensitivity.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 4 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a pragmatic triple blind (participant and parents, practitioners and analyst will be blinded), two arm, superiority, placebo controlled randomized trial with 1:1 allocation.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Participants in the treatment arm will receive a Xylitol syrup. | Other: Xylitol syrup<br>* Each dose will be 5 mL of 400 g/L and subjects will receive Three to 5 doses will be given each day.<br>|
| Placebo Comparator: Placebo<br>Participants in the placebo arm will receive sorbitol syrup. | Other: Placebo<br>* Each dose looks and tastes like the xylitol syrup but it is not microbial. Each dose will be 5 mL of 300 g/L of sorbitol. Three to 5 doses will be given each day.<br>* Other names: Sorbitol syrup;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acute otitis media episodes | Total number of physician diagnosed acute otitis media episodes | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| upper respiratory tract infection episodes | Total number of parent or caregiver reported upper respiratory tract infection episodes | 6 months | 
| dental caries | absence of dental caries by parent report | 6 months |