The Effect of a Multispecies Probiotic on Reducing the Incidence of Antibiotic-associated Diarrhoea in Children.

Not Applicable

Completed

• Conditions: Antibiotic-associated Diarrhea
• Interventions: Dietary Supplement: Multispecies probiotic; Other: Placebo

• Registration Number: NCT03334604
• Lead Sponsor: Medical University of Warsaw

Brief Summary

In this trial, the investigators aim to assess the effectiveness of a multispecies probiotic consisting of 2 strains of Bifidobacterium (B. bifidum W23, B. lactis W51) and 6 strains of Lactobacillus (L. acidophilus W37, L. acidophilus W55, L. paracasei W20, L. plantarum W62, L. rhamnosus W71, and L. salivarius W24) in reducing the risk of antibiotic-associated diarrhoea in a group of children undergoing antibiotic therapy for common infections.

Detailed Description

Certain individual probiotic strains have been proven to be effective in reducing the risk of antibiotic-associated diarrhoea (AAD). However, the effects of using multispecies probiotics remain unclear. The investigators aim to assess the effectiveness of a specific multispecies probiotic preparation (Ecologic AAD Kids) in reducing the incidence of AAD in children.

In this trial, a total of 350 children aged 3 months to 18 years, undergoing antibiotic treatment, will be randomly allocated to receive either a multispecies probiotic consisting of 2 strains of Bifidobacterium (B. bifidum W23, B. lactis W51) and 6 strains of Lactobacillus (L. acidophilus W37, L. acidophilus W55, L. paracasei W20, L. plantarum W62, L. rhamnosus W71, and L. salivarius W24) at a total dose of 10\^10 colony-forming units daily, or a placebo, from the first day of antibiotic treatment until 7 days after antibiotic cessation. The primary outcome measure will be the incidence of AAD, defined as ≥3 loose or watery stools (a score of A on the Amsterdam Infant Stool Scale for children younger than 1 year and a score of 5-7 on the Bristol Stool Form scale for children older than 1 year) in 24 hours, caused either by Clostridium difficile or of otherwise unexplained aetiology (after testing for common diarrhoeal pathogens), occurring during and/or up to 7 days after the end of the antibiotic therapy.

Study Timeline

• Study First Submitted: 2017-10-24
• Study First Submitted QC: 2017-11-02
• Study First Posted: 2017-11-07
• Study Start: 2018-02-16
• Status Verified: 2021-01
• Primary Completion: 2021-05-13
• Study Completion: 2021-05-13
• Last Update Submitted: 2021-09-29
• Last Update Posted: 2021-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

• children receiving oral or intravenous antibiotics for common infections, willing and able to start the probiotic intervention within 24 hours after the start of antibiotic intake, receiving broad-spectrum antibiotics (broad-spectrum penicillins, cephalosporins, fluoroquinolones, clindamycin).

Exclusion Criteria

• prior use of antibiotics within the previous 4 weeks, presence of a severe or generalised infection, history of severe chronic disease (e.g., cancer, inflammatory bowel disease, tuberculosis), critical/life-threatening illness, immunodeficiency, history of pre-existing diarrhoea within the previous 4 weeks, exclusive breastfeeding, allergy or hypersensitivity to any component of the study product, tube-feeding, use of proton-pump inhibitors, laxatives or anti-diarrhoeal drugs, as well as use of a probiotic product containing L rhamnosus GG or S boulardii 14 days before and during the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Multispecies probiotic group	Multispecies probiotic	175 participants.
Control group	Placebo	175 participants.

Primary Outcome Measures

Name	Time	Method
Incidence of antibiotic-associated diarrhea	Up to 7th day after antibiotic cessation.	Antibiotic-associated diarrhea will be defined as 3 or more loose or watery stools (a score of A on the Amsterdam Infant Stool Scale or 5-7 on the Bristol Stool Form scale) per day in a 24-hour period, caused by C. difficile infection or of otherwise unexplained aetiology after testing for common diarrhoeal pathogens (rotavirus, adenovirus, norovirus, Campylobacter spp., Salmonella spp., Shigella spp., and Yersinia spp.), occurring during the intervention period.

Secondary Outcome Measures

Name	Time	Method
Incidence of diarrhea	Up to 7th day after antibiotic cessation.	≥3 loose or watery stools per day for a minimum of 24 hours regardless of its aetiology.
Incidence of antibiotic-associated diarrhea - alternative definition 2	Up to 7th day after antibiotic cessation.	≥2 loose or watery stools per day for a minimum of a 24-hour period caused by C. difficile infection or of otherwise unexplained aetiology.
Clostridium difficile-associated diarrhea	Up to 7th day after antibiotic cessation.	≥3 loose or watery stools per day for a minimum of 24 hours caused by C. difficile confirmed by the presence of toxin-producing C. difficile in stools.
Incidence of antibiotic-associated diarrhea - alternative definition 1	Up to 7th day after antibiotic cessation.	≥3 loose or watery stools per day for a minimum of a 48-hour period caused by C. difficile infection or of otherwise unexplained aetiology.
Duration of diarrhea	Up to 7th day after antibiotic cessation.	Defined as the time until the normalisation of stool consistency according to the Bristol Stoo Form (BSF) or Amsterdam Infant Stool Scale (AISS) - on BSF numbers 1, 2, 3 and 4; on AISS scale, letters B or C, and the presence of normal stools for 48 h.
Discontinuation of the antibiotic treatment due to severity of diarrhoea	Up to 7th day after antibiotic cessation.
Need for intravenous rehydration	Up to 7th day after antibiotic cessation.
Hospitalisation caused by diarrhoea	Up to 7th day after antibiotic cessation.
Adverse events	Up to 7th day after antibiotic cessation.

Trial Locations

Locations (6)

OLVG location East; 🇳🇱 Amsterdam, Netherlands

Amsterdam UMC, location AMC; 🇳🇱 Amsterdam, Netherlands

Department of Paediatrics, The Medical University of Warsaw, Poland; 🇵🇱 Warsaw, Poland

Amsterdam UMC, location VUmc; 🇳🇱 Amsterdam, Netherlands

OLVG location West; 🇳🇱 Amsterdam, Netherlands

Department of Paediatrics, St. Hedwig of Silesia Hospital; 🇵🇱 Trzebnica, Silesia, Poland