Necrotizing Enterocolitis of NewbornNCT05710575
Role of Probiotic Use in Outcomes of Premature Birth
A study testing probiotic in people with Necrotizing Enterocolitis of Newborn, run by University of Health Sciences Lahore at 1 site in Pakistan.
Trial summary
Project Summary: The prevalence of preterm birth ranges from 5% to 18% across 184 countries, and an estimated 15 million infants are born preterm globally. These infants with an immature immune system and gastrointestinal tract are at risk of complications of premature birth, which is the leading cause of neonatal… Read more about this study
- Who is it for?
- Ages 28 to 36 weeksHealthy volunteers can take part
- Conditions the study is for
- Necrotizing Enterocolitis of Newborn
- What is being tested?
- probiotic
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 sitePakistan
- Study dates
- 20 Feb 2023to 10 Sep 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 to 36 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Premature infants with gestational age of more than 28 weeks and less than 36 weeks
- Birth weight of 1000 - 2500 grams
- Admitted to the neonatal intensive care unit (NICU) of Pediatric Medicine Unit II, Services hospital Lahore
- With intestinal feeding.
Who cannot join
- Infants with major congenital malformations (including congenital heart disease, gastrointestinal obstruction, gastroschisis, etc.)
- Congenital metabolic errors hypoxic ischemic encephalopathy (HIE) of grade two or more according to Sarnat scoring system (Gordon et al., 2020)
- Death in the first 72 hours of life
- Newborns of addicted mothers
- Postpartum age more than two weeks
- Parental unacceptance
Trial locations and contacts
1 site in 1 country.
About this study
Project Summary:
The prevalence of preterm birth ranges from 5% to 18% across 184 countries, and an estimated 15 million infants are born preterm globally. These infants with an immature immune system and gastrointestinal tract are at risk of complications of premature birth, which is the leading cause of neonatal death. According to researcher hypothesis for this study, there is role of probiotics in promoting food tolerance and reducing the incidence and severity of Necrotizing Enterocolitis (NEC) and death related to NEC in pre-term VLBW infants. In the current study, we will examine the effects of probiotics in premature infants and figure out the optimal intervention through randomized controlled trial (RCT).
Read more
A prospective, masked, randomized single blinded controlled trial will be conducted in the neonatal intensive care unit (NICU) of Services Hospital Lahore. In this trial the treatment group will receive the probiotics during their first month of life, and the control group will receive no treatment. Primary outcome will be the incidence of death or NEC (≥ stage 2). Death is included as a primary outcome because it is a competing variable of NEC. The x2 test will be used to analyze the categorical data, along with Fisher's exact test when applicable. The Student's t test will be used for continuous data. A logistic regression model will be used to analyze the treatment effects on the primary and secondary outcome variables (death, NEC, and sepsis). Values will be expressed for mean and standard deviation. Statistical significance is set at P-value of 0.05.
The objective of this study is to confirm the evidence and to get the more reliable and authentic results regarding the more effective treatment of NEC in preterm neonates. In this way, the researcher shall be able to improve the outcome of premature births and to reduce the complications by increasing the cure rate. Similarly, it will help the researcher to improve knowledge for better management of NEC in neonates.
Read the detailed description
Despite improvement in antenatal services, preterm births have remained a common but serious problem. In recent years because of environmental factors and increase rate of in vitro fertilization, the prevalence of preterm birth ranges from 5% to 18% across 184 countries, and globally, the number of infants with preterm birth is around 15 million. . These infants, with immature immune system and gastrointestinal tract, are at risk of complications of premature birth, which is a leading cause of neonatal death .
Recent studies suggest that the composition of infants' gut micro biota is affected by birth weight and gestational age. Altered gut micro biota has proven to be an important factor putting infants at high risk of developing necrotizing enterocolitis (NEC) and sepsis, which may lead to death and lifelong physical impairment. It is evident that early probiotic supplementation may benefit premature infants by improving their gastrointestinal tolerance against potential pathogens and regulating the altered gut micro biota to resemble that of a term healthy infant.
Probiotic with or without prebiotic supplementation is a practicable method among nutrition interventions and may support gut micro biota colonization growth, and long-term neurologic development in premature infants. Probiotic supplements in formula may regulate the stability and composition of premature infants' gut microbiota. Recent studies and meta-analyses suggest that probiotic intervention has some positive effects on premature infants, especially in reducing the mortality and morbidity of NEC and sepsis. Deshpande et al. showed that probiotics could reduce the risk of late-onset sepsis and NEC when Bifidobacterium or Lactobacillus was part of the supplementation through a subgroup analysis in pairwise meta-analysis, but the result was restricted to low- and middle-income countries. However, previous pairwise meta-analysis only focused on efficacy but could not find the most effective intervention method. It is suggested that there are different effects when different strains or combinations are used.
As numerous strains and preparations, including multi strains without given reasons, have been used in relevant trials, probiotic usage in infants needs to be regulated by more evidence. Previously published network meta-analyses in which authors compare the effect of different strains also have several shortcomings in their methodology or design. Thus, the authors of these studies did not point out which strain is an optimum option for infants' health and failed to provide powerful evidence for clinical use of probiotics. In the current study, the researchers will examine the effect of probiotics in premature infants and will figured out the optimal intervention through randomized controlled trial (RCT).
- Conditions
- Necrotizing Enterocolitis of Newborn
- Being tested
- probiotic, placebo
- Keywords
- probiotic, premature birth
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
probioticBiological
Probiotic or placebo administration will be started from the first feed of the infants. Infants in the probiotic group will receive five drops of oil-based suspension containing 1×108 colony-forming units of L reuteri (DSM 17938 Biogaia AB, Stockholm, Sweden) once a day, until death or discharge from the hospital. For infants on oral feeds, after suctioning oral secretions, five drops will be placed in the posterior oropharynx of the infants. For infants without per oral feeds, five drops will be administered through a gastric tube followed by a flash of 0.5 mL of sterile water. For the infants in the placebo group, five drops from an identical vial containing only oil base will be administered following the same protocol as the probiotic group.
placeboOther
Probiotic or placebo administration will be started from the first feed of the infants. Infants in the probiotic group will receive five drops of oil-based suspension containing 1×108 colony-forming units of L reuteri (DSM 17938 Biogaia AB, Stockholm, Sweden) once a day, until death or discharge from the hospital. For infants on oral feeds, after suctioning oral secretions, five drops will be placed in the posterior oropharynx of the infants. For infants without per oral feeds, five drops will be administered through a gastric tube followed by a flash of 0.5 mL of sterile water. For the infants in the placebo group, five drops from an identical vial containing only oil base will be administered following the same protocol as the probiotic group.
| Study group | Role | What they receive |
|---|---|---|
| probiotic group | Experimental | Probiotic or placebo administration will be started from the first feed of the infants. Infants in the probiotic group will receive five drops of oil-based suspension containing 1×108 colony-forming units of L reuteri (DSM 17938 Biogaia AB, Stockholm, Sweden) once a day, until death or discharge from the hospital. For infants on oral feeds, after suctioning oral secretions, five drops will be placed in the posterior oropharynx of the infants. For infants without per oral feeds, five drops will be administered through a gastric tube followed by a flash of 0.5 mL of sterile water. For the infants in the placebo group, five drops from an identical vial containing only oil base will be administered following the same protocol as the probiotic group. Receives: Biological: probiotic |
| placebo group | Experimental | Probiotic or placebo administration will be started from the first feed of the infants. Infants in the probiotic group will receive five drops of oil-based suspension containing 1×108 colony-forming units of L reuteri (DSM 17938 Biogaia AB, Stockholm, Sweden) once a day, until death or discharge from the hospital. For infants on oral feeds, after suctioning oral secretions, five drops will be placed in the posterior oropharynx of the infants. For infants without per oral feeds, five drops will be administered through a gastric tube followed by a flash of 0.5 mL of sterile water. For the infants in the placebo group, five drops from an identical vial containing only oil base will be administered following the same protocol as the probiotic group. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of participants who develop necrotizing enterocolitis
necrotizing enterocolitis will be stage according to bell's staging
Measured: 1 month
number of participants with prolonged hospital stay
length of hospital stay from day of admission to day of discharge according to medical records
Measured: 1 month
Secondary outcomes (2)
number of participants with culture proven sepsis
culture proven sepsis in premature infants after taking probiotics
Measured: 1 month
number of participants with feeding intolerance
premature infants unable to take feed and at what time infants achieve fll enteral feed
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2023
- Study start20 Feb 2023
- Primary completion10 Jun 2023
- Study completion10 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Necrotizing Enterocolitis of NewbornStudies of the same condition, open and under way.
- More trials run by University of Health Sciences LahoreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomization will be carried out in blocks of 10, and the list of random numbers will be generated by the subprogram Epitable from Epi-Info 6.04 (Centers for Disease Control and Prevention, Atlanta, GA). Two trained external personnel from the NICU will be responsible for obtaining this list and for randomly assigning the infants to the probiotics and control groups. A sealed envelope with the identification number in ascending order, containing information about which group they belonged to, will be provided for each infant and will be sent to the hospital's nutritional center. Three previously trained research assistants, who will not be a part of the neonatal team, will interview the mothers, recruit the infants, and they will also be responsible for sending the envelopes to the nutritional unit.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Health Sciences Lahore
- Sponsor type
- University, hospital or other
- Collaborators
- Services Institute of Medical Sciences, Pakistan
- Responsible party
- Principal investigator, Komal Khadim Hussain, University of Health Sciences Lahore
- Investigators
- komal khadim hussain, MBBS, Principal investigator, Services Institute of Medical Sciences, Pakistandr azhar farooq, MBBS,FCPS, Study chair, Services Institute of Medical Sciences, Pakistan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05710575
- Sponsor's protocol ID
- IRB/2022/920/SIMS
- Status last verified
- Sep 2025
- First submitted
- 13 Jan 2023
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Probiotic Use in Outcomes of Premature Birth
- ClinicalTrials.gov ID
- NCT05710575
- Acronym / sponsor ID
- IRB/2022/920/SIMS
- Conditions
- Necrotizing Enterocolitis of Newborn
- Keywords
- probiotic, premature birth
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University of Health Sciences LahoreUniversity, hospital or other
- Collaborators
- Services Institute of Medical Sciences, Pakistan
- Study start
- 20 Feb 2023 (actual)
- Primary completion
- 10 Jun 2023 (actual)
- Study completion
- 10 Sep 2023 (actual)
- First posted
- 2 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Project Summary:
The prevalence of preterm birth ranges from 5% to 18% across 184 countries, and an estimated 15 million infants are born preterm globally. These infants with an immature immune system and gastrointestinal tract are at risk of complications of premature birth, which is the leading cause of neonatal death. According to researcher hypothesis for this study, there is role of probiotics in promoting food tolerance and reducing the incidence and severity of Necrotizing Enterocolitis (NEC) and death related to NEC in pre-term VLBW infants. In the current study, we will examine the effects of probiotics in premature infants and figure out the optimal intervention through randomized controlled trial (RCT).
A prospective, masked, randomized single blinded controlled trial will be conducted in the neonatal intensive care unit (NICU) of Services Hospital Lahore. In this trial the treatment group will receive the probiotics during their first month of life, and the control group will receive no treatment. Primary outcome will be the incidence of death or NEC (≥ stage 2). Death is included as a primary outcome because it is a competing variable of NEC. The x2 test will be used to analyze the categorical data, along with Fisher's exact test when applicable. The Student's t test will be used for continuous data. A logistic regression model will be used to analyze the treatment effects on the primary and secondary outcome variables (death, NEC, and sepsis). Values will be expressed for mean and standard deviation. Statistical significance is set at P-value of 0.05.
The objective of this study is to confirm the evidence and to get the more reliable and authentic results regarding the more effective treatment of NEC in preterm neonates. In this way, the researcher shall be able to improve the outcome of premature births and to reduce the complications by increasing the cure rate. Similarly, it will help the researcher to improve knowledge for better management of NEC in neonates.
Detailed description
Despite improvement in antenatal services, preterm births have remained a common but serious problem. In recent years because of environmental factors and increase rate of in vitro fertilization, the prevalence of preterm birth ranges from 5% to 18% across 184 countries, and globally, the number of infants with preterm birth is around 15 million. . These infants, with immature immune system and gastrointestinal tract, are at risk of complications of premature birth, which is a leading cause of neonatal death .
Recent studies suggest that the composition of infants' gut micro biota is affected by birth weight and gestational age. Altered gut micro biota has proven to be an important factor putting infants at high risk of developing necrotizing enterocolitis (NEC) and sepsis, which may lead to death and lifelong physical impairment. It is evident that early probiotic supplementation may benefit premature infants by improving their gastrointestinal tolerance against potential pathogens and regulating the altered gut micro biota to resemble that of a term healthy infant.
Probiotic with or without prebiotic supplementation is a practicable method among nutrition interventions and may support gut micro biota colonization growth, and long-term neurologic development in premature infants. Probiotic supplements in formula may regulate the stability and composition of premature infants' gut microbiota. Recent studies and meta-analyses suggest that probiotic intervention has some positive effects on premature infants, especially in reducing the mortality and morbidity of NEC and sepsis. Deshpande et al. showed that probiotics could reduce the risk of late-onset sepsis and NEC when Bifidobacterium or Lactobacillus was part of the supplementation through a subgroup analysis in pairwise meta-analysis, but the result was restricted to low- and middle-income countries. However, previous pairwise meta-analysis only focused on efficacy but could not find the most effective intervention method. It is suggested that there are different effects when different strains or combinations are used.
As numerous strains and preparations, including multi strains without given reasons, have been used in relevant trials, probiotic usage in infants needs to be regulated by more evidence. Previously published network meta-analyses in which authors compare the effect of different strains also have several shortcomings in their methodology or design. Thus, the authors of these studies did not point out which strain is an optimum option for infants' health and failed to provide powerful evidence for clinical use of probiotics. In the current study, the researchers will examine the effect of probiotics in premature infants and will figured out the optimal intervention through randomized controlled trial (RCT).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Randomization will be carried out in blocks of 10, and the list of random numbers will be generated by the subprogram Epitable from Epi-Info 6.04 (Centers for Disease Control and Prevention, Atlanta, GA). Two trained external personnel from the NICU will be responsible for obtaining this list and for randomly assigning the infants to the probiotics and control groups. A sealed envelope with the identification number in ascending order, containing information about which group they belonged to, will be provided for each infant and will be sent to the hospital's nutritional center. Three previously trained research assistants, who will not be a part of the neonatal team, will interview the mothers, recruit the infants, and they will also be responsible for sending the envelopes to the nutritional unit.
| Arm | Type | Receives |
|---|---|---|
| probiotic group | Experimental | Biological: probioticProbiotic or placebo administration will be started from the first feed of the infants. Infants in the probiotic group will receive five drops of oil-based suspension containing 1×108 colony-forming units of L reuteri (DSM 17938 Biogaia AB, Stockholm, Sweden) once a day, until death or discharge from the hospital. For infants on oral feeds, after suctioning oral secretions, five drops will be placed in the posterior oropharynx of the infants. For infants without per oral feeds, five drops will be administered through a gastric tube followed by a flash of 0.5 mL of sterile water. For the infants in the placebo group, five drops from an identical vial containing only oil base will be administered following the same protocol as the probiotic group. |
| placebo group | Experimental | Other: placeboProbiotic or placebo administration will be started from the first feed of the infants. Infants in the probiotic group will receive five drops of oil-based suspension containing 1×108 colony-forming units of L reuteri (DSM 17938 Biogaia AB, Stockholm, Sweden) once a day, until death or discharge from the hospital. For infants on oral feeds, after suctioning oral secretions, five drops will be placed in the posterior oropharynx of the infants. For infants without per oral feeds, five drops will be administered through a gastric tube followed by a flash of 0.5 mL of sterile water. For the infants in the placebo group, five drops from an identical vial containing only oil base will be administered following the same protocol as the probiotic group. |
Who may qualify
- Ages
- 28 to 36 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Premature infants with gestational age of more than 28 weeks and less than 36 weeks
- Birth weight of 1000 - 2500 grams
- Admitted to the neonatal intensive care unit (NICU) of Pediatric Medicine Unit II, Services hospital Lahore
- With intestinal feeding.
Key exclusion criteria (6 listed)
- Infants with major congenital malformations (including congenital heart disease, gastrointestinal obstruction, gastroschisis, etc.)
- Congenital metabolic errors hypoxic ischemic encephalopathy (HIE) of grade two or more according to Sarnat scoring system (Gordon et al., 2020)
- Death in the first 72 hours of life
- Newborns of addicted mothers
- Postpartum age more than two weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| probioticProbiotic or placebo administration will be started from the first feed of the infants. Infants in the probiotic group will receive five drops of oil-based suspension containing 1×108 colony-forming units of L reuteri (DSM 17938 Biogaia AB, Stockholm, Sweden) once a day, until death or discharge from the hospital. For infants on oral feeds, after suctioning oral secretions, five drops will be placed in the posterior oropharynx of the infants. For infants without per oral feeds, five drops will be administered through a gastric tube followed by a flash of 0.5 mL of sterile water. For the infants in the placebo group, five drops from an identical vial containing only oil base will be administered following the same protocol as the probiotic group. | Biological | probiotic group |
| placeboProbiotic or placebo administration will be started from the first feed of the infants. Infants in the probiotic group will receive five drops of oil-based suspension containing 1×108 colony-forming units of L reuteri (DSM 17938 Biogaia AB, Stockholm, Sweden) once a day, until death or discharge from the hospital. For infants on oral feeds, after suctioning oral secretions, five drops will be placed in the posterior oropharynx of the infants. For infants without per oral feeds, five drops will be administered through a gastric tube followed by a flash of 0.5 mL of sterile water. For the infants in the placebo group, five drops from an identical vial containing only oil base will be administered following the same protocol as the probiotic group. | Other | placebo group |
Primary outcome
number of participants who develop necrotizing enterocolitis
Time frame: 1 month
necrotizing enterocolitis will be stage according to bell's staging
number of participants with prolonged hospital stay
Time frame: 1 month
length of hospital stay from day of admission to day of discharge according to medical records
2 secondary outcomes
number of participants with culture proven sepsis
Time frame: 1 month
number of participants with feeding intolerance
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
komal khadim hussain, MBBS principal investigator
Services Institute of Medical Sciences, Pakistan
dr azhar farooq, MBBS,FCPS study chair
Services Institute of Medical Sciences, Pakistan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing probiotic in people with Necrotizing Enterocolitis of Newborn, run by University of Health Sciences Lahore at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of participants who develop necrotizing enterocolitis (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2025.