Clinical trial NCT03334604: The Effect of a Multispecies Probiotic on Reducing the Incidence of Antibiotic-associated Diarrhoea in Children.
Official title: The Effect of a Multispecies Probiotic on Reducing the Incidence of Antibiotic-associated Diarrhoea in Children.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Antibiotic-associated Diarrhea
Keywords: antibiotic-associated diarrhea
probiotics
Lead sponsor: Medical University of Warsaw
Sponsor class: OTHER
Collaborators: name: Winclove Probiotics B.V.
First posted: 2017-11-07
Enrollment: 350
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of antibiotic-associated diarrhea
timeFrame: Up to 7th day after antibiotic cessation.
Secondary outcomes:
measure: Incidence of antibiotic-associated diarrhea - alternative definition 1
timeFrame: Up to 7th day after antibiotic cessation.
measure: Incidence of antibiotic-associated diarrhea - alternative definition 2
timeFrame: Up to 7th day after antibiotic cessation.
measure: Incidence of diarrhea
timeFrame: Up to 7th day after antibiotic cessation.
measure: Clostridium difficile-associated diarrhea
timeFrame: Up to 7th day after antibiotic cessation.
measure: Duration of diarrhea
timeFrame: Up to 7th day after antibiotic cessation.
measure: Discontinuation of the antibiotic treatment due to severity of diarrhoea
timeFrame: Up to 7th day after antibiotic cessation.
measure: Hospitalisation caused by diarrhoea
timeFrame: Up to 7th day after antibiotic cessation.
measure: Need for intravenous rehydration
timeFrame: Up to 7th day after antibiotic cessation.
measure: Adverse events
timeFrame: Up to 7th day after antibiotic cessation.
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: OLVG location West
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUmc
city: Amsterdam
country: Netherlands
facility: OLVG location East
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
city: Trzebnica
country: Poland
facility: Department of Paediatrics, St. Hedwig of Silesia Hospital
state: Silesia
city: Warsaw
country: Poland
facility: Department of Paediatrics, The Medical University of Warsaw, Poland
Study officials:
affiliation: Department of Paediatrics, The Medical University of Warsaw, Poland
name: Jan Łukasik, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lukasik J, Dierikx T, Besseling-van der Vaart I, de Meij T, Szajewska H; Multispecies Probiotic in AAD Study Group. Multispecies Probiotic for the Prevention of Antibiotic-Associated Diarrhea in Children: A Randomized Clinical Trial. JAMA Pediatr. 2022 Sep 1;176(9):860-866. doi: 10.1001/jamapediatrics.2022.1973.
citation: Lukasik J, Szajewska H. Effect of a multispecies probiotic on reducing the incidence of antibiotic-associated diarrhoea in children: a protocol for a randomised controlled trial. BMJ Open. 2018 Jun 4;8(5):e021214. doi: 10.1136/bmjopen-2017-021214.