Necrotizing Enterocolitis of NewbornPhase 4NCT07296718
Single Vs Multi-strain Probiotics for Preterm Neonates
A Phase 4 study testing Dextrose 10%, Lactobacillus Rhamnosus GG and Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4 in people with Necrotizing Enterocolitis of Newborn and Sepsis Newborn, run by Madiha, MPhil at 1 site in Pakistan.
Trial summary
The goal of this randomized control clinical trial is to determine if probiotics can prevent mortality and morbidity in preterm neonates. It also evaluates effects of probiotics on feeding pattern and growth. It will also learn about the comparative effects of single vs multiple strain probiotics. Read more about this study
- Who is it for?
- Ages Up to 36 weeks
- Conditions the study is for
- Necrotizing Enterocolitis of Newborn, Sepsis Newborn, Growth
- What is being tested?
- Dextrose 10%, Lactobacillus Rhamnosus GG and Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 249 participants
- Where
- 1 sitePakistan
- Study dates
- 15 May 2023to 15 Oct 2025
- Phase
- Phase 4
- 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 Up to 36 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm babies of gestational age <35+6days, birth weight <2500 grams, received and tolerated at-least one feed within 72 hours of birth and informed consent from parents or guardian.
Who cannot join
- Neonates with major congenital malformations, gastrointestinal anomalies, early onset sepsis (C-reactive protein (CRP) >10 mg/L in the first 72 h of life) and renal insufficiency
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Clinical and Growth-related Effects of Probiotics in Preterm Infants: A Randomized, Placebo Controlled Clinical Trial.
The goal of this randomized control clinical trial is to determine if probiotics can prevent mortality and morbidity in preterm neonates. It also evaluates effects of probiotics on feeding pattern and growth. It will also learn about the comparative effects of single vs multiple strain probiotics.
It aims to answer:
Read more
Does probiotics improve the health and growth outcomes in preterm neonates in our population? Does single vs multiple strain of probiotics have difference in effects?
Participants will:
Participants given either single strain or multiple strain probiotics for 28 days post birth.
Data about mortality, morbidity, feeding pattern and growth (weight, height, head circumference gain) recorded on daily basis.
Read the detailed description
This trial is single-centered, parallel, multi-arm, 1:1:1 randomized, blinded, placebo controlled clinical trial. It compares 3 groups; Group P1 (Placebo), Group P2-Single Strain probiotic (Lactobacillus rhamnosus GG) and Group P3- Multiple strains probiotic ( Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4) for preventing preterm neonatal morbidities, improving feeding tolerance and overall growth.
Primary objective: The primary objective of our trial will be to compare the incidence and severity of Necrotizing enterocolitis (NEC) from the time of trial participation till the end of trial treatment (28 days) according to Bell's grading criteria.
Secondary objectives:
All these outcomes will be measured from the day intervention started to the end of supplementation (28 days)
- To evaluate incidence of sepsis, intracerebral haemorrhage and periventricular leukomalacia, retinopathy of prematurity and bronchopulmonary dysplasia)
- To estimate the time to full enteral feeding (i.e., ≥150 ml/kg/day) and feeding tolerance based on Davy's Neonatal Feeding Assessment Scale (NFAS).
- To determine the effect of probiotics on growth (weight, height, and head circumference) of premature babies
- To assess comparative efficacy of single strain vs combination probiotics for aforementioned objectives
Framework/hypothesis: The experimental group P2 (Lactobacillus rhamnosus GG) and Group P3- ( Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4) are superior to control group (Placebo) as preventing NEC and other morbidities in preterm neonates, thus improving feeding tolerance and overall growth.
- Being tested
- Dextrose 10%, Lactobacillus Rhamnosus GG, Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4
- Keywords
- Probiotics, Preterm neonates, Single vs Multiple strain
- Medical subject headings
- Neonatal Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dextrose 10%Dietary supplement
Also called Placebo
P1
Lactobacillus Rhamnosus GGDrug
Also called Prepro GG
Single Strain
Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4Drug
Also called Amybact
Multiple Strain
| Study group | Role | What they receive |
|---|---|---|
| P1 | Placebo comparator | 1 ml of 10% dextrose water will be dispensed in 5cc syringe and administered orally or via feeding tube for 28 days. Receives: Dietary Supplement: Dextrose 10% |
| P2 | Active comparator | Single strain probiotic- Lactobacillus rhamnosus GG. The single dose 1.5×109 CFU/day as 1 mL of the reconstituted solution will be given every day via the feeding tube or orally as applicable until reaching feeds of 50 mL/kg/day. It will be increased thereafter to 3×109 CFU/day once feeds exceed 50mL/kg/day. Receives: Drug: Lactobacillus Rhamnosus GG |
| P3 | Active comparator | Multiple strain probiotic-Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4.
The single dose 1.5×109 CFU/day as 1 mL of the reconstituted solution will be given every day via the feeding tube or orally as applicable until reaching feeds of 50 mL/kg/day. It will be increased thereafter to 3×109 CFU/day once feeds exceed 50mL/kg/day. Receives: Drug: Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Necrotizing enterocolitis (NEC)
Bell's classification used for grading and diagnosis
Measured: From the day intervention started to day 28 of supplementation
Secondary outcomes (5)
Neonatal Sepsis
Clinical sepsis is defined as condition with at least two signs of systemic inflammatory response (e.g. temperature >38 C or <36.5 C, tachycardia > 200/min etc.), one laboratory sign (e.g. C-reactive protein >20mg/L) but no proof of causative agent in blood culture. Clinical sepsis with proof of blood culture positive for causative agent was defined as confirmed sepsis.
Measured: From the day intervention started to day 28 of supplementation
Feeding Intolerance
A gastrointestinal tolerance score, based on gastric residual volume, emesis, abdominal distension, number of stools and nil per oral days was calculated to identify and score feeding intolerance. Each score as 1. A score of >2 was considered gastric intolerance.
Measured: From the day intervention started to day 28 of supplementation
Weight
Weight measured in grams
Measured: From the day intervention started to day 28 of supplementation
Body length
Measured in millimeters daily once
Measured: From the day intervention started to day 28 of supplementation
Head Circumference
Measured in millimeters
Measured: From the day study started to day 28 of supplementation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2025
- Study start15 May 2023
- Primary completion15 Nov 2023
- Study completion15 Oct 2025
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.
- 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 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo-controlled randomized clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 249 participants (actual)
Sponsor and investigators
- Lead sponsor
- Madiha, MPhil
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Madiha, MPhil, The Islamia University of Bahawalpur, Khawaja Fareed CampusDr
- Investigators
- Imran Masood, PhD, Principal investigator, The Islamia University of Bahawalpur, Khawaja Fareed Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07296718
- Sponsor's protocol ID
- NEOPRO-SvsM
- Status last verified
- Dec 2025
- First submitted
- 19 Nov 2025
- Last updated
- 22 Dec 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 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Clinical and Growth-related Effects of Probiotics in Preterm Infants: A Randomized, Placebo Controlled Clinical Trial.
- ClinicalTrials.gov ID
- NCT07296718
- Acronym / sponsor ID
- NEOPRO-SvsM
- Keywords
- Probiotics, Preterm neonates, Single vs Multiple strain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 249 participants (actual)
- Lead sponsor
- Madiha, MPhilUniversity, hospital or other
- Study start
- 15 May 2023 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- 15 Oct 2025 (actual)
- First posted
- 22 Dec 2025 (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.
The goal of this randomized control clinical trial is to determine if probiotics can prevent mortality and morbidity in preterm neonates. It also evaluates effects of probiotics on feeding pattern and growth. It will also learn about the comparative effects of single vs multiple strain probiotics.
It aims to answer:
Does probiotics improve the health and growth outcomes in preterm neonates in our population? Does single vs multiple strain of probiotics have difference in effects?
Participants will:
Participants given either single strain or multiple strain probiotics for 28 days post birth.
Data about mortality, morbidity, feeding pattern and growth (weight, height, head circumference gain) recorded on daily basis.
Detailed description
This trial is single-centered, parallel, multi-arm, 1:1:1 randomized, blinded, placebo controlled clinical trial. It compares 3 groups; Group P1 (Placebo), Group P2-Single Strain probiotic (Lactobacillus rhamnosus GG) and Group P3- Multiple strains probiotic ( Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4) for preventing preterm neonatal morbidities, improving feeding tolerance and overall growth.
Primary objective: The primary objective of our trial will be to compare the incidence and severity of Necrotizing enterocolitis (NEC) from the time of trial participation till the end of trial treatment (28 days) according to Bell's grading criteria.
Secondary objectives:
All these outcomes will be measured from the day intervention started to the end of supplementation (28 days)
- To evaluate incidence of sepsis, intracerebral haemorrhage and periventricular leukomalacia, retinopathy of prematurity and bronchopulmonary dysplasia)
- To estimate the time to full enteral feeding (i.e., ≥150 ml/kg/day) and feeding tolerance based on Davy's Neonatal Feeding Assessment Scale (NFAS).
- To determine the effect of probiotics on growth (weight, height, and head circumference) of premature babies
- To assess comparative efficacy of single strain vs combination probiotics for aforementioned objectives
Framework/hypothesis: The experimental group P2 (Lactobacillus rhamnosus GG) and Group P3- ( Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4) are superior to control group (Placebo) as preventing NEC and other morbidities in preterm neonates, thus improving feeding tolerance and overall growth.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Placebo-controlled randomized clinical trial
| Arm | Type | Receives |
|---|---|---|
| P1 | Placebo comparator | Dietary Supplement: Dextrose 10%1 ml of 10% dextrose water will be dispensed in 5cc syringe and administered orally or via feeding tube for 28 days. |
| P2 | Active comparator | Drug: Lactobacillus Rhamnosus GGSingle strain probiotic- Lactobacillus rhamnosus GG. The single dose 1.5×109 CFU/day as 1 mL of the reconstituted solution will be given every day via the feeding tube or orally as applicable until reaching feeds of 50 mL/kg/day. It will be increased thereafter to 3×109 CFU/day once feeds exceed 50mL/kg/day. |
| P3 | Active comparator | Drug: Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4Multiple strain probiotic-Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4. The single dose 1.5×109 CFU/day as 1 mL of the reconstituted solution will be given every day via the feeding tube or orally as applicable until reaching feeds of 50 mL/kg/day. It will be increased thereafter to 3×109 CFU/day once feeds exceed 50mL/kg/day. |
Who may qualify
- Ages
- Up to 36 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Preterm babies of gestational age <35+6days, birth weight <2500 grams, received and tolerated at-least one feed within 72 hours of birth and informed consent from parents or guardian.
Key exclusion criteria (1 listed)
- Neonates with major congenital malformations, gastrointestinal anomalies, early onset sepsis (C-reactive protein (CRP) >10 mg/L in the first 72 h of life) and renal insufficiency
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 |
|---|---|---|
| Dextrose 10%Also: PlaceboP1 | Dietary supplement | P1 |
| Lactobacillus Rhamnosus GGAlso: Prepro GGSingle Strain | Drug | P2 |
| Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4Also: AmybactMultiple Strain | Drug | P3 |
Primary outcome
Necrotizing enterocolitis (NEC)
Time frame: From the day intervention started to day 28 of supplementation
Bell's classification used for grading and diagnosis
5 secondary outcomes
Neonatal Sepsis
Time frame: From the day intervention started to day 28 of supplementation
Feeding Intolerance
Time frame: From the day intervention started to day 28 of supplementation
Weight
Time frame: From the day intervention started to day 28 of supplementation
Body length
Time frame: From the day intervention started to day 28 of supplementation
Head Circumference
Time frame: From the day study started to day 28 of supplementation
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 22 Dec 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.
Imran Masood, PhD principal investigator
The Islamia University of Bahawalpur, Khawaja Fareed Campus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dextrose 10%, Lactobacillus Rhamnosus GG and Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4 in people with Necrotizing Enterocolitis of Newborn and Sepsis Newborn, run by Madiha, MPhil 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 1 inclusion and 1 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 22 Dec 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Necrotizing enterocolitis (NEC) (time frame: From the day intervention started to day 28 of supplementation). 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 22 Dec 2025.