L Rhamnosus ATCC 53103 & L Reuteri DSM 29063 Compared With L Rhamnosus ATCC 53103 for Preventing AAD in Children (FLOSTRUM)

A Two-strain Probiotic (L Rhamnosus ATCC 53103 & L Reuteri DSM 29063) Compared With a Single Strain Probiotic (L Rhamnosus ATCC 53103) for Preventing Antibiotic-associated Diarrhea: an Open-label, Randomized, Noninferiority Trial

This study will use a noninferiority design to examine whether the administration of L rhamnosus ATCC 53103 & L reuteri DSM 29063 (Flostrum Baby) is no worse than (or as good as) the administration of a recommended probiotic L rhamnosus ATCC 53103 (commercially available as Dicoflor, hereafter a reference product) for the prevention of antibiotic-associated diarrhea in children,

Study Overview

• Status: Not yet recruiting
• Conditions: Antibiotic-associated Diarrhea
• Intervention / Treatment: Dietary supplement: Lactobacillus rhamnosus ATCC 53103 & Lactobacillus reuteri DSM 29063; Dietary supplement: L rhamnosus ATCC 53103

Detailed Description

The recruitment will take place in hospitalized patients at the Pediatric Department of St. Hedwig of Silesia Hospital, Trzebnica, Poland. Additionally, patients treated at the out-patient clinics collaborating with the St. Hedwig of Silesia Hospital will be recruited. The involvement of other recruiting wards and/or sites are under consideration provided that the personnel are adequately trained and competent in conducting clinical trials. The start of the recruitment is planned in March 2020 and should be completed within the following 2 years.

The test product will be Flostrum Baby, which is a food supplement consisting of two bacterial strains: Lactobacillus rhamnosus ATCC 53103 and Lactobacillus reuteri DSM 29063, 5x10^9 CFU and 1x10^8 CFU, respectively, per seven drops.

The control product will be Dicoflor, which is a food supplement containing L rhamnosus ATCC 53103, 5x10^9 CFU, per five drops.

Caregivers will receive oral and written information regarding the study. Written informed consent will be obtained by the physicians involved in the study. Participants will be randomized within 24 hours after the initiation of the antibiotic administration.

Throughout the study period, healthcare providers and/or caregivers will record the number and consistency of stools in a standard stool diary. To record stool consistency, in children younger than 1 year, the Amsterdam Infant Stool Scale (AISS)9 will be used, and loose or watery stools will correspond to A-consistency. In children older than 1 year, the Bristol Stool Form (BSF) scale10 will be used, and loose or watery stools will correspond to scores of 5- 7. In the case of missing or incomplete data, data from hospital charts will be obtained. At any time, caregivers will have the right to withdraw the participating child from the study; they will be not obliged to give reasons for this decision, and there will be no effect on subsequent physician and/or institutional medical care.

In the event of loose or watery stools, the presence of viral or bacterial pathogens in the stool samples will be investigated. The presence of viral pathogens will be checked by using a standard rapid, qualitative, chromatographic immunoassay that simultaneously detects rotaviruses, adenoviruses, and noroviruses. Standard microbiological techniques will be used to isolate and identify bacterial pathogens (Salmonella spp, Shigella spp, Campylobacter spp, and Yersinia spp). C. difficile toxins A and B will be identified by standard enzyme immunoassay.

All study participants will be followed up for the duration of the intervention (antibiotic treatment) and then for up to 1 week after the intervention.

• Study Type: Interventional
• Enrollment (Anticipated): 892
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Krzysztof Korbecki, MPharm; Phone Number: +48 666 041 510; Email: Krzysztof.Korbecki@adamed.com

Study Locations

• Poland
  • Trzebnica, Poland, 55-100
    • Department of Paediatrics, St. Hedwig of Silesia Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. age younger than 18 years;
2. oral or intravenous antibiotic therapy which started within 24 hours of enrolment;
3. signed informed consent.

Exclusion criteria:

1. pre-existing acute or chronic diarrhea, history of chronic gastrointestinal disease (e.g. inflammatory bowel disease, cystic fibrosis, coeliac disease, food allergy) or other severe chronic diseases (eg, neoplastic diseases),
2. major medical problems (eg. immunocompromised, major developmental or genetic abnormality);
3. taking any of the study products (or probiotic strains included in the study products) at the time of study commencement;
4. use of antibiotics within 4 weeks prior to enrolment,
5. prematurity;
6. exclusive breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Flostrum Baby; The test product will be Flostrum Baby, which is a food supplement consisting of two bacterial strains: Lactobacillus rhamnosus ATCC 53103 and Lactobacillus reuteri DSM 29063, 5x10^9 CFU and 1x10^8 CFU, respectively, per seven drops. Flostrum Baby - in children below 12 years of age, 7 drops, twice daily; in children older than 12 years, 14 drops, twice daily.	Dietary supplement: Lactobacillus rhamnosus ATCC 53103 & Lactobacillus reuteri DSM 29063; 7 drops contain Lactobacillus rhamnosus GG 5x10^9 CFU; and Lactobacillus reuteri 1x10^8 CFU.; Other Names: Flostrum Baby
Active Comparator: Dicoflor; The control product will be Dicoflor, which is a food supplement containing L rhamnosus ATCC 53103, 5x10^9 CFU, per five drops. Dicoflor - the manufacturer recommends 5-10 drops daily, with no age specification. For the purposes of this study, 5 drops, twice daily, in children below 12 years of age; 10 drops, twice daily, in children older than 12 years.	Dietary supplement: L rhamnosus ATCC 53103; 5 drops contain Lactobacillus rhamnosus 5x10^9 CFU.; Other Names: Dicoflor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Antibiotic-associated diarrhea (3 or more loose or watery stools (a score of A on the AIS Scale or 5-7 on the BSF scale) per day in a 24-hour period, caused by C. difficile infection or of otherwise unexpla	From the date of randomisation up to 7th day after antibiotic cessation

Secondary Outcome Measures

Outcome Measure	Time Frame
• Any diarrhea (defined as ≥ 3 loose or watery stools per day for a minimum of 24 hours regardless of its etiology).	From the date of randomisation up to 7th day after antibiotic cessation
• C difficile-associated diarrhea (CDAD) (diarrhea defined as above caused by C. difficile confirmed by the presence of toxin-producing C. difficile in stools (positive toxin tests))	From the date of randomisation up to 7th day after antibiotic cessation
• The duration of diarrhea (defined as the time until the normalization of stool consistency according to the BSF or AISS scale (on BSF scale, numbers 1, 2, 3 and 4; on AISS scale, letters B or C), and the presence of normal stools for 48 hours).	From the date of randomisation up to 7th day after antibiotic cessation
• Discontinuation of the antibiotic treatment due to severity of diarrhea.	From the date of randomisation up to 7th day after antibiotic cessation
• Hospitalization caused by diarrhea in outpatient	From the date of randomisation up to 7th day after antibiotic cessation
• Adverse events.	From the date of randomisation up to 7th day after antibiotic cessation
Number and consistency of stools	From the date of randomisation up to 7th day after antibiotic cessation

Collaborators and Investigators

• Sponsor: Medical University of Warsaw
• Collaborators: Adamed Pharma S.A.
• Investigators: Study Chair: Hanna Szajewska, MD, The Medical Univ of Warsaw, Dept of Paediatrics; Principal Investigator: Henryk Szymański, MD, Pediatric Department of St. Hedwig of Silesia Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2020
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: February 10, 2020
• First Submitted That Met QC Criteria: February 18, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Diarrhea
• Other Study ID Numbers: FLOSTRUM2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No