Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT04836013 |
| Other study ID # |
52265 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 13, 2021 |
| Est. completion date |
April 13, 2022 |
Study information
| Verified date |
May 2021 |
| Source |
Università degli Studi dell'Insubria |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This is a prospective multicenter pediatric double-blind, randomized placebo-controlled,
parallel group clinical trial intended to evaluate the efficacy, safety and tolerability of a
combined probiotic (LGG and L. reuteri LMG P-27481) in the prevention of antibiotic
associated diarrhea and gastrointestinal symptoms in hospitalised children treated with
antibiotics for proven or suspected bacterial infection.
Description:
Eligible children will be randomly assigned to receive the combined probiotic study product
(Noos, Roma, Italia)(BCCMTM Bacterial Collection of Ghent, Belgium, Italian Patent:
102016000011071, International Patent Request : PCT/IB 2017/053856), or placebo as additional
treatment to the antibiotic therapy. Kind, dose and duration of antibiotic treatment will be
decided by the local clinicians according to good medical practice and current
recommendations. The first dose of probiotic will be started the same day of starting the
antibiotic treatment, immediately after enrollment. Then, each oral stick will be
administered orally once daily, in the morning, before breakfast, during the antibiotic
treatment and prolonged for 30 days since starting.
Study product The combined probiotic is made by Lactobacillus reuteri LMG P-27481 and
Lactobacillus rhamnosus GG (ATCC 53103), sucralose and isomalt as an oral stick formulation
of 1.6 g with a concentration of probiotic of 2x1010 colony forming unit (CFU) per stick,
launched in the Italian market with the name of Reuterin®GG (Noos, Roma, Italia).
The probiotic and placebo will be prepared centrally by the probiotic producer as identically
appearing oral stick. The placebo will contain only sucralose and isomalt, 1.6 g per stick.
Randomization The allocation sequences and randomization lists has been generated by a online
computer system. The probiotic -placebo allocation ratio will be of 1:1. To ensure allocation
concealment, an independent subject prepared the randomization schedule and sealed envelopes
to be sent to the participant centers. Each investigator will control the packaging and
labels of trial treatments sent by the producer with a numerical code with no possible
identification of the probiotic product compared to the placebo. The allocation will be
consecutively assigned for all enrolled subjects. All investigators, participants, and
statisticians will be blinded to the assigned treatment throughout the study and during the
data analysis. After completing the analysis of the data or in case of sever adverse event
the randomization code will be broken and information about the content of the product
(probiotic or placebo) will be revealed by the producer, upon the investigator's request.
Monitoring and collection of data At enrollment a standardized form will record age, gender,
anthropometric parameters, vital signs, refilling time, site of infection, laboratory tests,
kind, dose and route of administration of antibiotic, diet, previous AAD or other
gastrointestinal symptoms, comorbidity and associated treatment. Vesikary scale,
anthropometric measures, vital signs, refilling time will be also recorded in each patient at
enrollment and in case of occurrence of diarrhea. Bristol stool chart will be used to grade
the consistency of stools.
Parents or care givers of each children will be instructed to fill in a diary to record the
duration of antibiotic treatment and/or other treatment, the intake of the study product, the
frequency of daily bowel movements, the consistency of stools (according to the Bristol stool
scale), the frequency and intensity (according to a VAS scale, from 0 to 10) of abdominal
pain, the presence and duration of fever, vomiting or any other symptoms they considered
important, diet changes and general well being (according to a numerical 1-10 scale). The
diary will be completed daily for the duration of the probiotic treatment and then weekly
till the end of the study. After discharge from the hospital the absence from day care or
school, the need of new antibiotic treatment or re-hospitalization will be also noted. In
case of diarrhea, fever or other severe symptoms after hospital discharge parents will be
instructed to contact the local pediatrician and investigator for clinical evaluation and
stool analysis. A clinical visit will be scheduled in all recruited patients after 1, 3 and 6
months from enrollment.
Re-hospitalization will be required in case of severe infection, severe dehydration or
whenever considered necessary by clinicians.
Scheduled investigations In all cases presenting diarrhea at least three stool samples will
be collected and stool tests will be performed to detect viral, bacterial or C. difficile
pathogens. Blood and urine test or radiologial investigations will be decided by the local
clinician based on patient's clinical presentation and according to guidelines and good
clinical practice.
One additional sample of stools will be collected, whenever possible, in each patient at
enrollment, at 1, 3 and 6 months to evaluate fecal calprotectin to indirectly assess
intestinal inflammation. In a subgroup of patients (the first 30 recruited in each arms) two
other stool samples and a urine sample will be collected and stocked in freezer (-20° C) at
the same study point for possible future additional explorative analysis of fecal
inflammatory markers (lactoferrine, IgA, IL10 and TNF-α) and metabolomic profile (urine
metabolites).
The probiotic producer (Noos S.r.L, Roma, Italia) will gift the probiotic product and placebo
for the duration of the study for all children enrolled but has and will have no role in the
design and conduct of the study; collection, management, analysis, or interpretation of the
data; preparation, review, or approval of the manuscript; or the decision to submit the
manuscript for publication. The data of the enrolled subjects will be managed, stored and
property of the clinical investigators of the participant centers and of the coordinator
center and will be analysed and published anonymously and as aggregate, in the respect of the
current legislation on privacy.
