Single Vs Multi-strain Probiotics for Preterm Neonates

Madiha, MPhil

Status and phase: Completed; Phase 4

Conditions: Necrotizing Enterocolitis of Newborn; Feeding Intolerance; Sepsis Newborn; Growth

Treatments: Drug: Lactobacillus Rhamnosus GG; Dietary Supplement: Dextrose 10%; Drug: Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4

Study type: Interventional

Funder types: Other

Identifiers

NCT07296718

NEOPRO-SvsM

Details and patient eligibility

About

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.

Full 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.

Enrollment: 249 patients

Sex: All

Ages: Under 36 weeks old

Volunteers: No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

• 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 design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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249 participants in 3 patient groups, including a placebo group

P1

Placebo Comparator group

Description:

1 ml of 10% dextrose water will be dispensed in 5cc syringe and administered orally or via feeding tube for 28 days.

Treatment:

Dietary Supplement: Dextrose 10%

P2

Active Comparator group

Description:

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.

Treatment:

Drug: Lactobacillus Rhamnosus GG

P3

Active Comparator group

Description:

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.

Treatment:

Drug: Bifidobacterium BB-12, Lactobacillus paracasei, L casei-431, Streptococcus thermophilus TH-4