Novel Diagnostics and Probiotics to Improve Management of Paediatric Acute Gastroenteritis

Study Overview
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Brief Summary
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Many children admitted to hospital in Botswana without bloody diarrhoea are presumed to have viral gastroenteritis and so not treated with antibiotics - but they may indeed have a treatable cause for their illness. We will conduct a randomized trial to see if rapid testing using novel methods to identify potentially treatable causes of diarrhoea leads to improved outcomes. We will also be randomizing children to probiotic therapy versus placebo (the standard of care) to see if this treatment decreases the duration of diarrhoea. The proposed study is a pilot trial, necessary before embarking on a large multi-centre trial.

Official Title
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Rapid Diagnostics and Probiotic Therapy for Paediatric Acute Gastroenteritis - a Randomized, Factorial, Controlled, Placebo-controlled, Pilot Trial

Conditions
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Acute Gastroenteritis

Intervention / Treatment
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* Other: Rapid diagnostic
* Dietary Supplement: Probiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: acute non-bloody gastroenteritis Exclusion Criteria: diarrhoea > 14 days sepsis, pneumonia, UTI, meningitis requiring empiric antibiotic therapy malignancy, IBD known link to another patient with diarrhoea of defined aetiology transferred in already on antimicrobials live outside study area children with severe acute malnutrition will be eligible for diagnostic arm but not probiotic arm

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 60 Months

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: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rapid diagnostics and probiotic<br> | Other: Rapid diagnostic<br>* Specimens from rectal mucosa will be obtained using flocked swabs at enrolment. Those in 'rapid diagnostic' groups will have them tested using multiplex PCR the day of enrolment and participants with treatable pathogens will have antimicrobials provided. Those in 'delayed diagnostic' groups will have the swabs batched at tested at the conclusion of the study, being treated as per standard of care.<br>Dietary Supplement: Probiotic<br>* Lactobacillus reuteri suspended in vegetable oil, 5 drops/day (1 x 10e8 CFU) x 2 months<br>|
| Placebo Comparator: Rapid diagnostics and placebo<br> | Other: Rapid diagnostic<br>* Specimens from rectal mucosa will be obtained using flocked swabs at enrolment. Those in 'rapid diagnostic' groups will have them tested using multiplex PCR the day of enrolment and participants with treatable pathogens will have antimicrobials provided. Those in 'delayed diagnostic' groups will have the swabs batched at tested at the conclusion of the study, being treated as per standard of care.<br>Other: Placebo<br>* Identical in appearance to L. reuteri probiotic (same bottle), but simply vegetable oil. Dose is 5 drops/day x 2 months.<br>|
| Experimental: Delayed diagnostics and probiotic<br> | Dietary Supplement: Probiotic<br>* Lactobacillus reuteri suspended in vegetable oil, 5 drops/day (1 x 10e8 CFU) x 2 months<br>|
| Placebo Comparator: Delayed diagnostics and placebo<br> | Other: Placebo<br>* Identical in appearance to L. reuteri probiotic (same bottle), but simply vegetable oil. Dose is 5 drops/day x 2 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Height z-score (HAZ) adjusted for initial HAZ |  | 60 days post-enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality |  | 60 days post-enrollment | 
| environmental enteropathy score |  | 60 days post-enrollment | 
| duration of diarrhoea | Note that presence of diarrhoea will be checked daily during admission. Total duration of diarrhoea will be verified with the caregiver by telephone 7 days after the participant was discharged home. | estimated average duration   4 days. | 
| Weight z-score (WAZ) adjusted for initial WAZ |  | 60 days after enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diarrhoea, gastroenteritis, rapid diagnostics, probiotics, sub-Saharan Africa