Probiotic Supplementation in Extremely Preterm Infants in Scandinavia

NCT05604846 | Recruiting DMC

• 1 other identifier: 2022-3968
• Study Type: interventional
• Target: 1,600
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of this research is to determine whether supplementation with probiotics during the first weeks of life reduces the risk of necrotizing enterocolitis (NEC) and neonatal mortality and is safe to use among extremely preterm (EPT) infants born before gestational week 28. P: The study population include EPT infants (n= 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. I: This is a double-blinded multicenter randomized controlled trial where infants in the intervention group will as soon as they tolerate 3 mL breastmilk per feed receive a probiotic combination of Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus diluted in 3 mL breastmilk and given once daily until gestational week 34. C: The control group will receive 3 mL breastmilk without probiotic supplementation (blinded) daily. O: Primary outcome variables is a composite endpoint of incidence of NEC and mortality. Secondary outcomes include incidence of sepsis, duration of hospital stay, use of antibiotics, feeding tolerance, growth, and body composition after hospital discharge. Patient benefit: To provide evidence on the usage of probiotics among EPT infants that are not currently covered by clinical recommendations. As EPT infants have the highest risk for NEC and mortality our results have the potential to change current recommendations and improve patient outcomes, decrease mortality, shorten hospitalization, and decrease overall health-care costs.

Conditions

Necrotizing Enterocolitis; Death; Sepsis Newborn; Feeding Disorder Neonatal; Growth Acceleration

Keywords

Probiotics; NEC; Extreme prematurity; Feeding tolerance

Outcome Measures

Primary Outcomes (2)

• Necrotizing enterocolitis (NEC)

  verified NEC \>/= Bell sage II

  Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks.

• Death

  Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks

Secondary Outcomes (5)

• Sepsis

  Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks

• Anibiotic use

  Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks

• Anibiotic use

  Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks

• Feeding intolerance

  Depending on gestational age at birth (22+0 wGA - 27+6 wGA) up to the end of intervention at 34 w GA + 2 weeks. This gives a time frame of 8-14 weeks

• Gut microbiome analysis

  immediately after inclusion, 14 days of life, 34 week of gestational age and 12 months corrected age.

Study Arms (2)

Probiotic group

EXPERIMENTAL

Probiotic group: 0,5 g per day of ProPrems®, including a combination of Bifidobacterium infantis Bb-02 (DSM 33361) 300 million, Bifidobacterium lactis (BB-12®) 350 million and Streptococcus thermophilus (TH-4®) 350 million. Mixed with 3 mills of breastmilk

Dietary Supplement: ProPrems

Control group

PLACEBO COMPARATOR

Control group receives 3 mills of breastmilk without additives

Dietary Supplement: ProPrems

Interventions

ProPrems DIETARY_SUPPLEMENT

The intervention product, commercially known as ProPrems®, is a combination of (one billion freeze-dried bacteria per 0.5 g in a maltodextrin base powder: Bifidobacterium infantis Bb-02 (DSM 33361) 300 million, Bifidobacterium lactis (BB-12®) 350 million, and Streptococcus thermophilus (TH-4®) 350 million will be given daily once to eligable infants born extremly preterm (\<28weeks of gestation) once they tolerate 3ml of enterla feeds until the age of 34 weeks of gestation.

Control group; Probiotic group

Eligibility Criteria

• Age: 22 Weeks - 28 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All extremly preterm infants born beween gestational age 22+0 to 27+6

You may not qualify if:

• Patients with severe complications and low chance of survival detected wihin the first 72 hours of life
• Patients with major congenital-anomalies
• Patients included in other interventional trials with the same or overlapping oucome measures.

Sponsors & Collaborators

• Region Stockholm: lead

Study Sites (1)

Karolinska University Hospital

Solna, Stockholm County, 17176, Sweden

RECRUITING

Related Publications (1)

• Kruth SS, Willers C, Persad E, Sjostrom ES, Lagerstrom SR, Rakow A. Probiotic supplementation and risk of necrotizing enterocolitis and mortality among extremely preterm infants-the Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial: study protocol for a multicenter, double-blinded, placebo-controlled, and registry-based randomized controlled trial. Trials. 2024 Apr 12;25(1):259. doi: 10.1186/s13063-024-08088-8.

  PMID: 38610034 DERIVED

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Death; Neonatal Sepsis

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Sepsis; Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation

Central Study Contacts

Alexander Rakow, MD PhD

CONTACT

+46725968444; alexander.rakow@regionstockholm.se

Sofia Söderquist-Kruth

CONTACT

+46738034038; sofia.soderquist-kruth@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Alexander Rakow MD PhD, Principal Investigator, Clinical Director Department of Neonatology, Karolinska University Hospital

Model Details: Randomized parallel-armed controlled trial (RCT) Registry based, double-blinded

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: November 3, 2022
• Study Start: December 16, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 16, 2023

Record last verified: 2023-10

Locations

SE (1)