Human Milk Fortification in Extremely Preterm Infants

NCT03797157 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: RegionOstergotland
• Study Type: interventional
• Target: 229
• Locations: 1 country
• Sites: 5

Brief Summary

This is a randomised controlled multi-centre trial comparing the effect of diet supplementation of a human breast milk-based nutrient fortifier (H2MF®) with standard bovine protein-based nutrient fortifier in 222 extremely preterm infants (born before gestational week 28+0) exclusively fed with human breast milk (own mother´s milk and/or donor milk). The infants will be randomised to receive either the human breast-milk based H2MF® or the standard bovine protein-based nutrient fortifier when oral feeds have reached \<100 ml/kg/day. The randomised intervention, stratified by centre, will continue until the target gestational week 34+0. The infant must not be fed with formula during the intervention period. The allocation will be concealed before inclusion, but after randomisation the study is not blinded. Primary endpoint of the intervention is the composite variable necrotizing enterocolitis (NEC), sepsis and mortality. The enrolled infants are characterised with clinical data including growth, feeding intolerance, use of enteral and parenteral nutrition, treatment, antibiotics and complications collected daily in a study specific case report form from birth until discharge from the hospital (not longer than gestational week 44+0). A follow up focusing on neurological development, growth and feeding problems will be performed at 2 years of age (corrected) and 5.5 years of age.

Conditions

Necrotizing Enterocolitis; Sepsis; Mortality

Outcome Measures

Primary Outcomes (1)

• The incidence of the composite of necrotizing enterocolitis, culture-proven sepsis and mortality

  An infant should have had any of these diagnoses to fulfil the criterion

  From birth until discharge from hospital (but not longer than gestational week 44+0)

Secondary Outcomes (52)

• The incidence of the composite of necrotizing enterocolitis and culture-proven sepsis

  From birth until discharge from hospital (but not longer than gestational week 44+0)

• The incidence of the composite of necrotizing enterocolitis culture-proven sepsis, bronchopulmonary dysplasia, retinopathy of prematurity and mortality (Mortality and morbidity index)

  From birth until discharge from hospital (but not longer than gestational week 44+0)

• Time to reach full enteral feeds

  From birth until discharge from hospital (but not longer than gestational week 44+0)

• Number of feeding interruptions

  From birth until discharge from hospital (but not longer than gestational week 44+0)

• Numbers of days with parenteral nutrition

  From birth until discharge from hospital (but not longer than gestational week 44+0)

Study Arms (2)

H2MF

EXPERIMENTAL

Human milk-based breast milk fortifier

Dietary Supplement: H2MF

Standard fortifier

ACTIVE COMPARATOR

Standard care: bovine milk-based breast milk fortifier

Dietary Supplement: Bovine milk-based fortifier

Interventions

H2MF DIETARY_SUPPLEMENT

H2MF is a human milk-based breastmilk fortifier for preterm infants

H2MF

Bovine milk-based fortifier DIETARY_SUPPLEMENT

Bovine milk-based fortifier is the standard breast milk fortifier in Sweden

Standard fortifier

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Gestational age at birth 22+0-27+6: based on prenatal ultrasonography.
• Enteral feeds \< 100 mL/kg/day at the day of randomisation.
• Written informed consent from the legal guardians of the infant.
• The home clinic of the infant has the logistics of maintaining the intervention until gestational week 34+0

You may not qualify if:

• Participation in another intervention trial aiming at having an effect on growth, nutrition, feeding intolerance or severe complications such as NEC and sepsis
• Infants having nutrient fortifier or formula prior to randomisation

Sponsors & Collaborators

• Thomas Abrahamsson, MD, PhD: lead
• Sahlgrenska University Hospital: collaborator
• Region Uppsala: collaborator
• Vasterbottens lans landsting: collaborator
• Prolacta Bioscience: collaborator
• Region Stockholm: collaborator

Study Sites (5)

Queen Silvia Children´s Hospital

Gothenburg, Sweden

Location

Crown Princess Victoria Children´s Hospital

Linköping, Sweden

Location

Karolinska Hospital

Stockholm, Sweden

Location

Norrlands Universitetssjukhus

Umeå, Sweden

Location

Akademiska Barnsjukhuset

Uppsala, Sweden

Location

Related Publications (2)

• Jensen GB, Domellof M, Ahlsson F, Elfvin A, Naver L, Abrahamsson T. Effect of human milk-based fortification in extremely preterm infants fed exclusively with breast milk: a randomised controlled trial. EClinicalMedicine. 2024 Jan 2;68:102375. doi: 10.1016/j.eclinm.2023.102375. eCollection 2024 Feb.

  PMID: 38545091 DERIVED

• Jensen GB, Ahlsson F, Domellof M, Elfvin A, Naver L, Abrahamsson T. Nordic study on human milk fortification in extremely preterm infants: a randomised controlled trial-the N-forte trial. BMJ Open. 2021 Nov 23;11(11):e053400. doi: 10.1136/bmjopen-2021-053400.

  PMID: 34815288 DERIVED

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Sepsis

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Thomas R Abrahamsson, MD, PhD

  Region Östergötland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator, MD PhD

Study Record Dates

• First Submitted: December 17, 2018
• First Posted: January 9, 2019
• Study Start: February 1, 2019
• Primary Completion: September 1, 2022
• Study Completion (Estimated): January 31, 2029
• Last Updated: July 23, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (5)