Optimizing the Management of Acute Diarrhoeal Disease

Study Overview
=================
Brief Summary
-----------------
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. The investigators will conduct a randomized trial to see if rapid testing using novel methods to identify potentially treatable causes of diarrhoea leads to improved outcomes. The investigators will also be randomizing children to Lactobacillus reuteri DSM (daughter strain) 17938 therapy versus placebo (the standard of care) to see if this treatment decreases the duration of diarrhoea. The proposed study is a large multi-centre trial following the previous pilot trial.

Official Title
-----------------
Optimizing the Management of Pediatric Acute Diarrhoeal Disease in Botswana

Conditions
-----------------
Acute Gastroenteritis

Intervention / Treatment
-----------------
* Other: Rapid diagnostics
* Biological: Probiotic
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: acute diarrhoeal illness (>= 3 stools in 24 hour period) Exclusion Criteria: diarrhoeal illness >=14 days bloody stool known inflammatory bowel disease, cystic fibrosis, or malignancy live in a household with someone else documented to have a bacterial or parasitic enteric infection of defined aetiology live outside catchment areas no permanent address no access to mobile phone previous participation in this study nosocomial diarrhoea

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapid diagnostics and probiotic<br>Participants randomized to this arm will have rapid enteric diagnostics performed on the day of enrolment. Those found to have a treatable pathogen will be prescribed antimicrobials that day. Participants will also be given Lactobacillus reuteri DSM 17938 5 x 10e8 cfu/mL x 60 days. | Other: Rapid diagnostics<br>* Participants will have enteric specimens obtained using a flocked rectal swab, which will be transported in 2 mL Cary Blair medium. These will be tested using the BioMerieux BioFire FilmArray GI panel.<br>Biological: Probiotic<br>* The probiotic given will be Lactobacillus reuteri DSM 17938, 5x10e8 cfu/mL x 60 days, suspended in vegetable oil.<br>|
| Other: Rapid diagnostics and placebo<br>Participants randomized to this arm will have rapid enteric diagnostics performed on the day of enrolment. Those found to have a treatable pathogen will be prescribed antimicrobials that day. Participants will also be given placebo x 60 days. | Other: Rapid diagnostics<br>* Participants will have enteric specimens obtained using a flocked rectal swab, which will be transported in 2 mL Cary Blair medium. These will be tested using the BioMerieux BioFire FilmArray GI panel.<br>Other: Placebo<br>* The placebo will be the vegetable oil vehicle and look identical to the probiotic.<br>|
| Other: No rapid diagnostics and probiotic<br>Participants randomized to this arm will have stool specimens processed after the conclusion of the study. Participants will also be given Lactobacillus reuteri DSM 17938 5 x 10e8 cfu/mL x 60 days. | Biological: Probiotic<br>* The probiotic given will be Lactobacillus reuteri DSM 17938, 5x10e8 cfu/mL x 60 days, suspended in vegetable oil.<br>|
| Placebo Comparator: No rapid diagnostics and placebo<br>Participants randomized to this arm will have stool specimens processed after the conclusion of the study. Participants will also be given placebo x 60 days. | Other: Placebo<br>* The placebo will be the vegetable oil vehicle and look identical to the probiotic.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 60 days post-enrollment | 
| Weight z-score (WAZ) adjusted for baseline WAZ |  | 60 days post-enrollment | 
| Environmental enteropathy score (EES) | composite of stool neopterin, myeloperoxidase, and alpha-1-antitrypsin | 60 days | 
| Diarrhoea recurrence |  | 60 days after enrolment | 

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