Determining the effect of probiotic supplements on hyperbilirubinemia in term neonates
Design
A double-blind three-arm parallel group randomized phase 3 clinical trial with a control group of 81 patients.
Settings and conduct
Neonates with hyperbilirubinemia hospitalized at Shahid Beheshti Hospital in Kashan will be included in the study. Patients will be assigned into three groups receiving placebo, Reuteflor, or Ramnoflor. Outcomes will be evaluated at the beginning of the intervention and after 24, 48, 72, and 96 hours. Researchers and participants will be blinded to the type of intervention.
Participants/Inclusion and exclusion criteria
Inclusion criteria:
1) 35 to 42 weeks of gestation
2) Birth weight between the 10th and 90th percentile
3) Newborns aged from birth to 14 days
4) Hyperbilirubinemia based on Bhutani Nomogram
Exclusion criteria:
1) Unwillingness to cooperate (lack of parental consent)
2) Taking antibiotics
3) Any acute or active infection
4) Occurrence of any side effects
5) Not consuming breast milk exclusively
6) Thyroid disorders
7) Presence of respiratory distress
8) NICU admission
9) Congenital heart disease
10) The presence of hemolysis, hemoglobinopathies, and hemolytic blood diseases such as G6PD deficiency, blood group incompatibility
11) Cephal hematoma and subgaleal hemorrhage
12) Phenobarbital consumption by the mother in the last month of pregnancy
13) Non-physiological hyperbilirubinemia
14) Presence of a life-threatening congenital disorder
15) Blood exchange
16) Outpatient treatment
Intervention groups
Patients will be assigned to three groups receiving Ramnoflor (n=24), Reuteflor (n=24) or placebo (n=33). Once daily and each time 5 drops of Ramnoflor (Lactobacillus Rhamnosus) or Reuteflor (Lactobacillus Reuteri) or placebo will be given to each group, respectively.
Main outcome variables
Total bilirubin; Direct bilirubin; Indirect bilirubin
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20230816059167N1
Registration date:2023-08-21, 1402/05/30
Registration timing:prospective
Last update:2023-08-21, 1402/05/30
Update count:0
Registration date
2023-08-21, 1402/05/30
Registrant information
Name
Fatemeh Rahemi
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 31 5546 1276
Email address
rahemi-f@kaums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-08-23, 1402/06/01
Expected recruitment end date
2023-10-22, 1402/07/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Investigating the effect of probiotic supplements on hyperbilirubinemia in term neonates
Public title
Investigating the effect of probiotics on neonatal jaundice
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
35 to 42 weeks of gestation
Birth weight between 10th and 90th percentile
Newborns aged from birth to 14 days
Hyperbilirubinemia based on Bhutani Nomogram
Exclusion criteria:
Unwillingness to cooperate (lack of parental consent)
Taking antibiotics
Any acute or active infection
Occurrence of any side effects
Not consuming breast milk exclusively
Thyroid disorders
Presence of respiratory distress
NICU admission
Congenital heart disease
The presence of hemolysis, hemoglobinopathies, and hemolytic blood diseases such as G6PD deficiency, blood group incompatibility
Cephal hematoma and subgaleal hemorrhage
Phenobarbital consumption by the mother in the last month of pregnancy
Non-physiological hyperbilirubinemia
Presence of a life-threatening congenital disorder
Blood exchange
Outpatient treatment
Age
From 1 day old to 14 days old
Gender
Both
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Sample size
Target sample size:
81
Randomization (investigator's opinion)
Randomized
Randomization description
In order to randomly allocate patients among groups, first, the table of random numbers is extracted from the Stattrek website (https://stattrek.com/statistics/random-number-generator.aspx) and then these numbers are assigned to groups using the block randomization method.
Blinding (investigator's opinion)
Double blinded
Blinding description
All three drops of Ramnoflor, Reuteflor, and placebo received from Fara Daru Fanavar Mehr (Farabiotic) company and prepared in packages with the same appearance and are coded (A, B, or C) by individuals who have no role in the study. During the study, the parents of the studied neonates and the researchers are blinded to the type of intervention.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics committee of Kashan University of Medical Sciences
Street address
Kashan University of Medical Sciences, Pezeshk Boulevard, Ghotbe Ravandi Boulevard, Kashan
City
Kashan
Province
Isfehan
Postal code
8715988141
Approval date
2023-07-16, 1402/04/25
Ethics committee reference number
IR.KAUMS.MEDNT.REC.1402.093
Health conditions studied
1
Description of health condition studied
Neonatal hyperbilirubinemia
ICD-10 code
P59.9
ICD-10 code description
Neonatal jaundice, unspecified
Primary outcomes
1
Description
Total Bilirubin
Timepoint
At the beginning of the study and 24, 48, 72 and 96 hours after the intervention
Method of measurement
Serum total bilirubin (mg/mL)
2
Description
Direct Bilirubin
Timepoint
At the beginning of the study and 24, 48, 72 and 96 hours after the intervention
Method of measurement
Serum direct bilirubin (mg/mL)
3
Description
Indirect Bilirubin
Timepoint
At the beginning of the study and 24, 48, 72 and 96 hours after the intervention
Method of measurement
Serum indirect bilirubin (mg/mL)
Secondary outcomes
1
Description
Length of hospital stay
Timepoint
At the time of discharge
Method of measurement
Days
2
Description
Defecation
Timepoint
on a daily basis from the day the intervention started until 96 hours later
Method of measurement
Number of defecations per day
3
Description
Complications including allergic reactions, gastrointestinal complications and ...
Timepoint
on a daily basis from the day the intervention started until 96 hours later
Method of measurement
History taking and physical examination
Intervention groups
1
Description
1st Intervention group: Once daily and each time 5 drops of probiotic supplement containing Lactobacillus Reuteri prepared by Fara Daru Fanavar Mehr (Farabiotic) pharmaceutical company under the brand name Reuteflor. Each 5 drops of Reuteflor contains 8x(10^8) lyophilized active cells of Lactobacillus Reuteri. This drop does not contain ingredients of mother's milk.
Category
Treatment - Drugs
2
Description
2nd Intervention group: Once daily and each time 5 drops of probiotic supplement containing Lactobacillus Rhamnosus prepared by Fara Daru Fanavar Mehr (Farabiotic) pharmaceutical company under the brand name Ramnoflor. Each 5 drops of Ramnoflor contains 8x(10^8) lyophilized active cells of Lactobacillus Rhamnosus. This drop does not contain ingredients of mother's milk.
Category
Treatment - Drugs
3
Description
Control group: Once daily and each time 5 drops of the placebo drop containing the base composition of probiotic drops without active ingredients. Placebo drops prepared by Fara Daru Fanavar Mehr (Farabiotic)