The effect of early oral probiotics prescription on feeding intolerance, regain birth weight and secondary outcomes in very low birth weight (VLBW) infants
The effect of early oral probiotics prescription on feeding intolerance, regain birth weight and secondary outcomes in very low birth weight infants.
Design
Two blinded randomized clinical trial with control group, phase 3 on 300 very low birth weight neonates. Stratify Block Randomization is used for randomization. Function rand of Microsoft Excel would be used For randomization.
Settings and conduct
This study will be performed in the neonatal intensive care unit of Mahdieh Hospital in Tehran. This study evaluated the early administration of oral probiotics on feeding intolerance, incidence of sepsis, incidence of necrotizing enterocolitis and length of hospital stay in these infants. Infants are continuously checked by special checklist designed by the researcher. For blinding, placebo drops are used in front of drug drops with the same packaging, with non-sequential and indistinguishable coding for people who do not have access to the key. The parents of the baby, the doctor or the nurse prescribing the medicine are blinded.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Hospitalization in neonatal intensive care unit, Born weight less than 1500 gr, Stable hemodynamic status, Ability to enteral nutrition, Parent's written consent.
Exclusion criteria: Dissatisfaction of parents, Unstable clinical status.
Intervention groups
In this study, very low birth weight infants placed in two groups of intervention and control randomly and the intervention from the first day of birth at the first 2 hours and once daily, before or after milk feeding and for 14 days in the groups. In the intervention group, probiotic is prescribed 5 drops per day and the placebo is prescribed in control group that Contains maltodextrin which is quite similar to the drug in terms of color, smell and taste and it is 5 drops too.
Main outcome variables
Feeding intolerance
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20220505054746N1
Registration date:2022-08-04, 1401/05/13
Registration timing:prospective
Last update:2022-08-04, 1401/05/13
Update count:0
Registration date
2022-08-04, 1401/05/13
Registrant information
Name
Fatemeh Heydari
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 28 3367 3982
Email address
f.heydari@qums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2022-08-23, 1401/06/01
Expected recruitment end date
2024-08-22, 1403/06/01
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The effect of early oral probiotics prescription on feeding intolerance, regain birth weight and secondary outcomes in very low birth weight (VLBW) infants
Public title
The effect of early oral probiotics prescription in very low birth weight (VLBW) infants
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
Hospitalization in NICU ward
Born weight less than 1500 gr
Stable hemodynamic status
Ability to enteral nutrition
Parent's written consent
Exclusion criteria:
Dissatisfaction of parents
Impossibility of starting standard nutrition for neonate
Existence of any congenital anomalies in neonate
Neonate's CPR need in labor room
Unstable clinical status
Being a child of mothers with substance abuse disorders
Severe abdominal distension or peptic hemorrhage
Immunodeficiency in the family of neonate
Congenital enteral perforation or atresia
Complete forbidding of oral feeding
Age
From 1 day old to 2 days old
Gender
Both
Phase
3
Groups that have been masked
Participant
Care provider
Sample size
Target sample size:
300
Randomization (investigator's opinion)
Randomized
Randomization description
In order to homogenize the patients in terms of the intervening variables of mechanical ventilation (invasive-non-invasive) and type of nutrition (breast milk-formula) and to create a balance in the number of samples allocated to each of the studied groups, sampling method was used by random sampling. It is stratified block randomization. So that before starting the study, we first adjust the number of floors based on different levels of two qualitative variables. In this study, we will have 4 floors as follows.
First class: patients who have aggressive ventilation and breast milk feeding.
Second class: patients who have non-invasive ventilation and breast milk feeding.
Third class: patients who have non-invasive ventilation and formula nutrition.
Fourth class: patients who have aggressive ventilation and formula nutrition.
We consider the sample size of each tier to be 75 to achieve a sample size of 300. For each class separately, we perform randomized block sampling. We consider the capacity of the blocks as 4 and then we write all the possible permutations for this block, which are defined as follows.
(1: ABAB) and (2: AABB) and (3: BBAA) and (4: BABA) and (5: ABBA) and (6: BAAB)
By means of a dice, we choose one of the numbers 1 to 6 and consider the corresponding block. For example, if the first random selection of block 5 is selected, the first person will receive treatment A, the second and third persons will receive treatment B, and the fourth person will receive treatment A. To reach a sample size of 75 per stratum, we continue this process 19 times. After selecting all the blocks, we randomly assign index A to one of the treatment groups. At the end, we merge the samples of all classes together and use the total sample for analysis.
Blinding (investigator's opinion)
Double blinded
Blinding description
The placebo drop is used against the drug with the same packaging, with non -sequential coding for people who do not have access to the key. Parents of the neonate and doctor or indicator nurse have been blinded and will be contacted by the original researcher if needed, and at the end of the study and completion of the questionnaires, they will be identified by the code.
Placebo
Used
Assignment
Other
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Shahid Beheshti University of Medical Sciences
Street address
Shahid Beheshti University of Medical Sciences, Velenjak Blvd., Tehran, Iran.
City
Tehran
Province
Tehran
Postal code
1985717443
Approval date
2022-02-06, 1400/11/17
Ethics committee reference number
IR.SBMU.RETECH.REC.1400.1068
Health conditions studied
1
Description of health condition studied
Very Low Birth Weight
ICD-10 code
P07.0
ICD-10 code description
Extremely low birth weight newborn
2
Description of health condition studied
1_2.499 weight
ICD-10 code
P07.1
ICD-10 code description
Other low birth weight newborn
3
Description of health condition studied
feeding intolerance
ICD-10 code
P92.5
ICD-10 code description
Neonatal difficulty in feeding at breast
4
Description of health condition studied
Abdominal distension
ICD-10 code
ICD-10 code description
P14
5
Description of health condition studied
vomiting
ICD-10 code
ICD-10 code description
P11
6
Description of health condition studied
Digestive bleeding
ICD-10 code
ICD-10 code description
P54.3
7
Description of health condition studied
necrotic enterocolitis
ICD-10 code
ICD-10 code description
P77
8
Description of health condition studied
Sepsis
ICD-10 code
ICD-10 code description
P36.9
Primary outcomes
1
Description
Feeding intolerance
Timepoint
In each feeding time
Method of measurement
Checklist
Secondary outcomes
1
Description
Sepsis
Timepoint
Daily
Method of measurement
Based on having clinical and specific symptoms of sepsis (including irritability of the baby, rapid breathing or apnea, changes in the skin color of the baby, diarrhea, poor sucking, poor feeding) and positive result of blood culture and CRP result recorded in the checklist in daily evaluations.
2
Description
Necrotic Enterocolitis
Timepoint
Daily
Method of measurement
Based on having clinical and specific symptoms of Necrotizing Enterocolitis (including lethargy, increased volume of food residue, bloody or bilious vomiting, ileus, persistent abdominal distension, bloody stools, symptoms of peritonitis and shock) and the Bells scale, which is evaluated in the checklist designed by the researcher.
3
Description
Time of hospitalization
Timepoint
Daily
Method of measurement
Checklist
4
Description
Time to reach total nutrition
Timepoint
Daily
Method of measurement
The days required to reach enteral nutrition of 100 milliliter per kilogram per day are evaluated with the checklist made by the researcher.
5
Description
Reach to born weight
Timepoint
Daily
Method of measurement
The weight of the infant will be assessed in terms of grams (in grams) until the clinical condition stabilizes and then daily until the day of discharge from the hospital. At the end of the weighting process, each premature infant will be assessed using Fenton growth charts. All measurements will be performed with a digital scale for fixed infants with the help of a researcher and will be recorded in a checklist created by the researcher.
Intervention groups
1
Description
Intervention group: early administration of oral probiotics in infants with very low birth weight. In this study, infants with very low birth weight from the first day of birth in the first 24 hours and once a day, before or after feeding with milk (in breastfeeding intervals) and for 14 days in the probiotic intervention group (containing Bifidobacterium lactis 3 5*100000000 colony forming units (CFU) and Bifidobacterium infantis 3.5*100000000 CFU and Streptococcus thermophilus 3*100000000 CFU) which is prepared in 700 mg sachets with maltodexerin and is 5 drops per day. It should be mentioned that this product is made by Farabiotic company.
Category
Prevention
2
Description
Control group: administration of placebo in babies with very low birth weight. In this study, babies with very low birth weight from the first day of birth, in the first 24 hours and once a day, before or after feeding with milk (in breastfeeding intervals) and for 14 days in the control group, placebo (containing maltodextrin, which is The color, smell and taste are completely similar to the medicine) which is prepared in 700 mg sachets and is prescribed in the amount of 5 drops. It should be mentioned that this product is made by Farabiotic Company.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Mahdiyeh Educational Hospital
Full name of responsible person
Naeeme Taslimi Taleghani
Street address
Fadayiane Eslam St, Shosh Square, Tehran
City
Tehran
Province
Tehran
Postal code
1185817311
Phone
+98 21 5506 2628
Email
mahdiyeh_hospital@sbmu.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Shahid Beheshti University of Medical Sciences
Full name of responsible person
Afshin Zarghi
Street address
Next to Taleghani Hospital,Shahid Arabi Street,Yemen Street, Shahid Chamran Highway,
City
Tehran
Province
Tehran
Postal code
1985717443
Phone
+98 21 23871
Email
info@sbmu.ac.ir
Grant name
Research Assistant of Shahid Beheshti University of Medical Sciences
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?