The effects of probiotic supplementation on intestinal permeability, inflammatory factors and clinical status in pediatrics with severe sepsis: a randomized double blind clinical trial
Determining the effect of probiotic supplementation on intestinal permeability biomarkers, inflammatory factors and clinical status of children with severe sepsis
Design
A phase 2 randomized double blind, controlled, parallel clinical trial on 44 patients. Stratified Permuted Block Randomization according to NPO status will be performed.
Settings and conduct
The current study will be conducted on children with severe sepsis in a children's medical center. The study subjects will be assigned to two probiotic supplement and placebo groups based on the NPO variable using the Stratified Permuted Block Randomization method. For children in the intervention group, Kidilact probiotic supplement (Kidilact VSL#3) will be prescribed two sachets of 1 gram per day for 7 days, and for the placebo group, a placebo that is completely similar to the probiotic supplement in terms of shape and color.
At the beginning and end of the study, 5 ml of venous blood will be taken from the patients to evaluate biochemical indicators, and anthropometric and clinical characteristics will also be collected.
Participants/Inclusion and exclusion criteria
Inclusion criteria:
Age between 1 and 12 years; Diagnosis of severe sepsis
Exclusion criteria:
Admission more than 72 hours in the PICU; Ileus, overt gastrointestinal bleeding, anatomic obstruction; Gastrointestinal diseases; Probiotic use one month before entering the study; Use of steroids and other immunosuppressive drugs; Suffering from immunosuppressive diseases; Severe acute malnutrition; Discharged from the hospital; Gastrointestinal and allergic reactions; Disagreement of the patient's parents
Intervention groups
Intervention group: Probiotics (Kidilact: including several probiotic bacteria.
Control group: Placebo (Corn starch)
The effects of probiotic supplementation on intestinal permeability, inflammatory factors and clinical status in pediatrics with severe sepsis: a randomized double blind clinical trial
Public title
Probiotic supplementation and sepsis
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Aged 1-12 years old
Diagnosis of severe sepsis according to pediatric sepsis consensus conference 2005 criteria in children admitted to PICU
Exclusion criteria:
PICU admission more than 72 hours
Ileus, overt gastrointestinal bleeding, anatomic obstruction of the gastrointestinal tract (eg, volvulus, intestinal atresia), recent esophageal or gastrointestinal surgery
Gastrointestinal diseases such as celiac disease, inflammatory bowel disease (IBD), short bowel syndrome (SBS), irritable bowel syndrome (IBS)
Use of feeding routes leading to jejunum such as jejunostomy
Probiotic use one month before entering the study
Use of steroids and other immunosuppressive drugs
Suffering from immunosuppressive diseases such as malignant tumors, acquired immunodeficiency syndrome, etc.
Severe acute malnutrition (According to the World Health Organization: Z-Score weight for height/length and BMI less than -3 SD average child growth standards WHO
Age
From 1 year old to 12 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Data and Safety Monitoring Board
Sample size
Target sample size:
44
Randomization (investigator's opinion)
Randomized
Randomization description
Random allocation will be done by Stratified Permuted Block Randomization method. Stratification is done based on the NPO variable. Eligible people who meet the criteria for entering the study, are selected, and then the two groups are randomly divided into 4 or 6 intervention blocks at a ratio of 1:1. Then, the list of blocks is divided equally between the two strata. Block randomization (4 or 6 people in each block) is done using the website www.randomization.com. In this way, the letters A and B will be spread between the patient codes. Numbers will be assigned to patients according to the order of participants' entry, and patients will be enrolled in the study based on special letters (A and B).
Blinding (investigator's opinion)
Double blinded
Blinding description
Blinding of patients: due to the fact that in this study, the patients are children under 12 years old and usually do not have optimal GCS, people in each group do not know the type of intervention.
In order to blind the researcher, the probiotic supplements and placebo will be delivered to the supervisor by the bio-fermentation company. Probiotic and placebo supplements are similar in appearance and packaging.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Children's Medical Center-Tehran University of Medical sciences
Street address
Children's Medical Center, Dr Gharib St, Keshavarz Blvd, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1419733151
Approval date
2023-08-09, 1402/05/18
Ethics committee reference number
IR.TUMS.CHMC.REC.1402.084
Health conditions studied
1
Description of health condition studied
Severe sepsis
ICD-10 code
R65.2
ICD-10 code description
Severe sepsis
Primary outcomes
1
Description
Serum Zonulin
Timepoint
Measurement of the serum level of zonulin in the initial study (before the start of the intervention) and 7 days after the start of probiotic consumption
Method of measurement
ELISA
2
Description
Serum LPS-Binding Protein
Timepoint
Measurement of the serum level of lipopolysaccharide binding protein (LBP) in the initial study (before the start of the intervention) and 7 days after the start of probiotic consumption
Method of measurement
ELISA
3
Description
Serum IL-6
Timepoint
Measurement of the serum level of Interleukin 6 (IL-6) in the initial study (before the start of the intervention) and 7 days after the start of probiotic consumption
Method of measurement
ELISA
4
Description
Serum IL-10
Timepoint
Measurement of the serum level of Interleukin 10 (IL-10) in the initial study (before the start of the intervention) and 7 days after the start of probiotic consumption
Method of measurement
ELISA
5
Description
Serum CRP
Timepoint
Measurement of the serum level of C-reactive protein (CRP) in the initial study (before the start of the intervention) and 7 days after the start of probiotic consumption
Method of measurement
ELISA
Secondary outcomes
1
Description
Duration of starting nutrition
Timepoint
The effect of probiotic supplementation on the length of starting nutrition duration of the study (7 days)
Method of measurement
Questionnaire forms
2
Description
The number of days to reach the nutritional goal
Timepoint
The effect of probiotic supplementation on the number of days to reach the nutritional goal duration of the study (7 days)
Method of measurement
Questionnaire forms
3
Description
Nutrition intolerance
Timepoint
The effect of probiotic supplementation on nutrition intolerance duration of the study (7 days)
Method of measurement
Questionnaire forms
4
Description
Need to vasoactive agents
Timepoint
The effect of probiotic supplementation on need to vasoactive agents duration of the study (7 days)
Method of measurement
Questionnaire forms
5
Description
The length of vasoactive use
Timepoint
The effect of probiotic supplementation on the length of vasoactive use duration of the study (7 days)
Method of measurement
Questionnaire forms
6
Description
Vasoactive inotropic score
Timepoint
The effect of probiotic supplementation on vasoactive inotropic score duration of the study (7 days)
Method of measurement
Calculation
7
Description
Need to mechanical ventilation
Timepoint
The effect of probiotic supplementation on need to mechanical ventilation duration of the study (7 days)
Method of measurement
Questionnaire forms
8
Description
The length of using mechanical ventilation
Timepoint
The effect of probiotic supplementation on the length of using mechanical ventilation duration of the study (7 days)
Method of measurement
Questionnaire forms
9
Description
Antibiotics use
Timepoint
The effect of probiotic supplementation on antibiotics use duration of the study (7 days)
Method of measurement
Questionnaire forms
10
Description
The length of antibiotic use
Timepoint
The effect of probiotic supplementation on the length of antibiotic use duration of the study (7 days)
Method of measurement
Questionnaire forms
11
Description
Treatment-related infection incidence
Timepoint
The effect of probiotic supplementation on treatment-related infection incidence duration of the study (7 days)
Method of measurement
Questionnaire forms
12
Description
Type of treatment-related infection
Timepoint
The effect of probiotic supplementation on type of treatment-related infection duration of the study (7 days)
Method of measurement
Questionnaire forms
13
Description
Change in incidence of Multiple Organ Dysfunction Syndrome (MODS)
Timepoint
The effect of probiotic supplementation on change in incidence of Multiple Organ Dysfunction Syndrome (MODS) duration of the study (7 days)
Method of measurement
Calculation
14
Description
The length of PICU stay
Timepoint
The effect of probiotic supplementation on the length of PICU stay duration of the study (7 days)
Method of measurement
Questionnaire forms
15
Description
Mortality
Timepoint
The effect of probiotic supplementation on mortality duration of the study (7 days)
Method of measurement
Questionnaire forms
Intervention groups
1
Description
Intervention group: Probiotic (KidiLact ZistTakhmir Company); Lactobacillus rhamnosus, Lactobacillus rotrilactobacillus Acidophilus, Lactobacillus bulgarico, Lactobacillus caseibifidobacterium infantis, Bifidobacterium brohbifidobacterium, Bifidobacterium bifidombifidobacterium, Lactistreptococcus thermophilus, 109 CFU per sachet, 1 gram, twice a day; Probiotics will be given in doses of one sachet twice a day with an interval of 12 hours for 7 days orally or through enteral feeding through a Nasogastric or Orogastric tube depending on the clinical condition of the patients. became. To prepare the supplement, mix the contents of one sachet in 5 ml of sterile water and use immediately.
Category
Treatment - Drugs
2
Description
Control group: placebo (corn starch); Placebo wasgiven in doses of one 1 gram sachet twice a day with an interval of 12 hours for 7 days orally or through enteral feeding through Nasogastric or Orogastric tube depending on the clinical condition of the patients. will be. To prepare, mix the contents of one sachet in 5 ml of sterile water and use immediately.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Children's medical center
Full name of responsible person
Masoud Mohammadpour
Street address
Children's Medical Center, Dr Gharib St, Keshavarz Blvd, Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 21 6693 0024
Email
cmcpr@tums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Hossein Imani
Street address
chool of Nutritional Sciences & Dietetics, Tehran University of Medical Sciences, No: 44 Hojjat-dost Alley, Naderi St.
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 21 8895 5742
Email
Info@snsd.tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Maryam Safabakhsh
Position
PhD student
Latest degree
Master
Other areas of specialty/work
Nutrition
Street address
School of Nutritional Sciences & Dietetics, Tehran University of Medical Sciences, No: 44 Hojjat-dost Alley, Naderi St.
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 912 263 8696
Email
maryam.safa@yahoo.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Maryam Safabakhsh
Position
PhD student
Latest degree
Master
Other areas of specialty/work
Nutrition
Street address
School of Nutritional Sciences & Dietetics, Tehran University of Medical Sciences, No: 44 Hojjat-dost Alley, Naderi St.
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 912 263 8696
Email
maryam.safa@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Maryam Safabakhsh
Position
PhD student
Latest degree
Master
Other areas of specialty/work
Nutrition
Street address
School of Nutritional Sciences & Dietetics, Tehran University of Medical Sciences, No: 44 Hojjat-dost Alley, Naderi St.
City
Tehran
Province
Tehran
Postal code
1419733151
Phone
+98 912 263 8696
Email
maryam.safa@yahoo.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD