Optimizing the Management of Acute Diarrhoeal Disease

Optimizing the Management of Pediatric Acute Diarrhoeal Disease in Botswana

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.

Study Overview

• Status: Completed
• Conditions: Acute Gastroenteritis
• Intervention / Treatment: Other: Rapid diagnostics; Biological: Probiotic; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 3

Contacts and Locations

Study Locations

• Botswana
  • Gaborone, Botswana
    • Princess Marina Hospital
  • Mochudi, Botswana
    • Deborah Retief Hospital
  • Molepolole, Botswana
    • Scottish Livingstone Hospital
  • Ramotswa, Botswana
    • Bamalete Lutheran Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rapid diagnostics and probiotic; 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; 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.; Biological: Probiotic; The probiotic given will be Lactobacillus reuteri DSM 17938, 5x10e8 cfu/mL x 60 days, suspended in vegetable oil.
Other: Rapid diagnostics and placebo; 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; 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.; Other: Placebo; The placebo will be the vegetable oil vehicle and look identical to the probiotic.
Other: No rapid diagnostics and probiotic; 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; The probiotic given will be Lactobacillus reuteri DSM 17938, 5x10e8 cfu/mL x 60 days, suspended in vegetable oil.
Placebo Comparator: No rapid diagnostics and placebo; 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; The placebo will be the vegetable oil vehicle and look identical to the probiotic.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: University of British Columbia; Grand Challenges Canada; BioMérieux; BioGaia AB; Copan Italia S.A.; Botswana-UPenn Partnership
• Investigators: Principal Investigator: Jeffrey Pernica, MD, McMaster University

Publications and helpful links

General Publications

• Pernica JM, Arscott-Mills T, Steenhoff AP, Mokomane M, Moorad B, Bapabi M, Lechiile K, Mangwegape O, Batisani B, Mawoko N, Muthoga C, Vanniyasingam T, Ewusie J, Lowe A, Bonsu JM, Gezmu AM, Smieja M, Mazhani L, Stordal K, Thabane L, Kelly MS, Goldfarb DM. Optimising the management of childhood acute diarrhoeal disease using a rapid test-and- treat strategy and/or Lactobacillus reuteri DSM 17938: a multicentre, randomised, controlled, factorial trial in Botswana. BMJ Glob Health. 2022 Apr;7(4):e007826. doi: 10.1136/bmjgh-2021-007826.

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 16, 2016
• First Posted (Estimate): June 17, 2016

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 23, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: probiotics; diarrhoea; gastroenteritis; rapid diagnostics
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis
• Other Study ID Numbers: GCC 0768-05