Necrotizing EnterocolitisPhase 2/3N-forteNCT03797157
Human Milk Fortification in Extremely Preterm Infants
A Phase 2/3 study testing H2MF and Bovine milk-based fortifier in people with Necrotizing Enterocolitis and Sepsis, run by Thomas Abrahamsson, MD, PhD at 5 sites in Sweden.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Necrotizing Enterocolitis, Sepsis, Mortality
- What is being tested?
- H2MF and Bovine milk-based fortifier
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 229 participants
- Where
- 5 sitesSweden
- Study dates
- 1 Feb 2019to 31 Jan 2029
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Lethal or complicated malformation known at the time of inclusion
- Chromosomal anomalies known at the time of inclusion
- No realistic hope for survival at the time of inclusion
- Gastrointestinal malformation known at the time of inclusion
- Abdominal surgery before the time of inclusion
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Sweden5 sites
Queen Silvia Children´s Hospital
Gothenburg
Crown Princess Victoria Children´s Hospital
Linköping
Karolinska Hospital
Stockholm
Norrlands Universitetssjukhus
Umeå
Akademiska Barnsjukhuset
Uppsala
About this study
Official title: Nordic Study on Human Milk Fortification in Extremely Preterm Infants: a Randomized Controlled Trial
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.
Read more
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.
Read the detailed description
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. If fortification with extra enteral lipids is needed during the intervention period, the infants receiving H2MF® will be supplemented with the human milk-based Prolact CR®, while the infants receiving standard bovine protein-based fortification will be supplemented with the standard lipid products used at the unit. The study subject will be enrolled at level III neonatal intensive care unit (NICU)s. Only infants with a home clinic with the logistics to maintain the intervention until gestational week 34+0 will be included.
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. It would not be possible to prescribe the fortifier and prepare of the breast milk in a blinded fashion, since the fortifiers are not exactly equal in nutrient content and also look different. Instead the assessment of several of the outcomes will be made blinded, such as the assessment of X-ray images in NEC cases.
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.
Since it is often difficult to distinguish between the diagnoses of NEC and sepsis, and their clinical consequences, the investigator's primary endpoint of the intervention is the composite variable NEC, sepsis and mortality. Secondary endpoints are feeding intolerance and other severe complication such as Bronchopulmonary dysplasia (BPD), Retinopathy of prematurity (ROP) and neurological impairment. Stool, urine and blood samples are also collected for microbiology, metabolomic and immunology analysis in order to study underlying mechanisms. Health economic analyses will be made to evaluate the costs and benefits of an introduction of human milk-based fortifier in NICUs in the Nordic countries.
Analyses will be conducted using an intention to treat approach. An evaluation will be performed when 20 infants have been included to evaluate feasibility and make it possible to adjust the protocol for the remaining part of the study. Safety analyses will be performed by an independent data and safety monitoring board (DSMB) when 50, 100 and 150 infants have been included. A sample size re-estimation will be made by an independent statistician when 150 infants have been included. Thus, the definitive sample size might be increased (never decreased) based on this interim analysis. The study can be terminated before 322 infants have been enrolled based on a decision of the sponsor and the DSMB, if the primary outcome is significantly lower (with a significance level <0.001) in the H2MF® than in the standard fortification group in the interim analysis made after 150 infants have completed the neonatal period. The study subject will be enrolled at level III NICUs in the Nordic Countries. All study subjects will be followed during the neonatal period until discharge (not longer than gestational week 44+0) and also be included in a follow up at 2 and 5.5 years of age based on the national follow up program for extremely preterm infants.
- Conditions
- Necrotizing Enterocolitis, Sepsis, Mortality
- Being tested
- H2MF, Bovine milk-based fortifier
- Medical subject headings
- Enterocolitis, Necrotizing, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
H2MFDietary supplement
H2MF is a human milk-based breastmilk fortifier for preterm infants
Bovine milk-based fortifierDietary supplement
Bovine milk-based fortifier is the standard breast milk fortifier in Sweden
| Study group | Role | What they receive |
|---|---|---|
| H2MF | Experimental | Human milk-based breast milk fortifier Receives: Dietary Supplement: H2MF |
| Standard fortifier | Active comparator | Standard care: bovine milk-based breast milk fortifier Receives: Dietary Supplement: Bovine milk-based fortifier |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
An infant should have had any of these diagnoses to fulfil the criterion
Measured: 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)
An infant should have had any of these diagnoses to fulfil the criterion
Measured: From birth until discharge from hospital (but not longer than gestational week 44+0)
Time to reach full enteral feeds
The day of life the infant has received at least 150 mL/kg enteral feeds
Measured: From birth until discharge from hospital (but not longer than gestational week 44+0)
Number of feeding interruptions
Number of days feedings held for ≥12 hours or feeds reduced by >50% (ml/kg/d) not due to a clinical procedure or transitioning to the breast
Measured: From birth until discharge from hospital (but not longer than gestational week 44+0)
Numbers of days with parenteral nutrition
Number of days of parental amino acid and/or lipid infusion. Only days when the enteral feed <150mL/kg/day should be included
Measured: From birth until discharge from hospital (but not longer than gestational week 44+0)
Number of large gastric aspirates per day
≥100% pre-feed volume (2 hours feeding volume if continuous feeding). Lower limit=2 ml/kg.
Measured: From birth until discharge from hospital (but not longer than gestational week 44+0)
Stool frequency
Measured: From birth until discharge from hospital (but not longer than gestational week 44+0)
Time to regain birth weight
Measured: From birth until discharge from hospital (but not longer than gestational week 44+0)
Change in head circumference in centimeters
Measured: At 7, 14, 21 and 28 days, the end of intervention (gestational week 34+0), gestational week 36+0, at discharge from neonatal ward (or at gestational week 44+0, whatever comes first) and at 2 years of age (corrected) and 5.5 years of age (uncorrected).
Change in weight in gram
Measured: At 7, 14, 21 and 28 days, the end of intervention (gestational week 34+0), gestational week 36+0, at discharge from neonatal ward (or at gestational week 44+0, whatever comes first) and at 2 years of age (corrected) and 5.5 years of age (uncorrected).
Change in length in centimeters
Measured: At 7, 14, 21 and 28 days, the end of intervention (gestational week 34+0), gestational week 36+0, at discharge from neonatal ward (or at gestational week 44+0, whatever comes first) and at 2 years of age (corrected) and 5.5 years of age (uncorrected).
The mortality incidence
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of necrotising enterocolitis: Bell´s stage II-III
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence spontaneous intestinal perforation
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of abdominal surgery
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence culture-proven sepsis
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of suspected sepsis, not culture-proven
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of pneumonia
Pathological X-ray confirmed by an independent radiologist, need of increased respiratory support/oxygen and laboratory inflammatory response
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of bronchopulmonary dysplasia
Need of extra oxygen, continuous positive air pressure (CPAP) or ventilator at gestational week 36+0
Measured: At gestational week 36+0
The incidence of retinopathy of the prematurity
Classified into stage I-V. The diagnosis is set after gestational week 42+0
Measured: From birth until gestational week 42+0
The incidence of intraventricular haemorrhage
Classified into grade I-IV according to Papile
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of periventricular leukomalacia
Criteria according to de Vries
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
Number of days with intensive care
Need of respirator or CPAP until discharge (not later than gestational week 44+0).
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
Length of stay at the hospital
Gestational week and day at discharge (not later than gestational week 44+0).
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
Length of need of feeding tube
Gestational week and day when the infant does not need it anymore (not later than gestational week 44+0)
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
Neurocognitive development at 2 years
Bayleys III, PARCA-R (Parental Report of Children´s Abilities-Revised) and ASQ-3 (Ages and stages questionnaire)
Measured: At 2 years of age
Prevalence of cerebral palsy at 2 years
Measured: At 2 years of age
Prevalence of epilepsy at 2 years
Measured: At 2 years of age
Prevalence of squint and/or impaired vision at 2 years
Measured: At 2 years of age
Prevalence of impaired hearing at 2 years
Measured: At 2 years of age
The number of infants needing extra oxygen and/or ventilatory support after discharge from the hospital at the neonatal period
Measured: From gestational week 44 until 2 years of age
The incidence of wheeze and/or asthma
Measured: From birth until 2 years of life
The incidence of severe infections after discharge from the neonatal unit
Measured: From gestational week 44 until 2 years of age
The number of infants needing feeding tube after discharge from the hospital at the neonatal period
Measured: From gestational week 44 until 2 years of age
The number of infants needing extra nutritional support after discharge from the hospital at the neonatal period
Measured: From gestational week 44 until 2 years of age
The prevalence of neurocognitive development at 5.5 years
Wechsler Preschool and Primary Scale of Intelligence IV (WPPSI-IV TM) and Movement ABC-2: the total scale points as well as the points of sub scales (motor, cognitive, language) will be presented. The prevalence of infants with a realist below 2 standard deviations will be defined to have mental retardation.
Measured: At 5.5 years of age
The prevalence of cerebral palsy at 5.5 years
Measured: At 5.5 years of age
The prevalence of epilepsy at 5.5 years of age
Measured: At 5.5 years of age
The prevalence of squint and/or impaired vision at 5.5 years of age
Measured: At 5.5 years of age
The prevalence of children with impaired hearing at 5.5 years of age
Measured: At 5.5 years of age
The prevalence of wheeze and/or asthma at 5.5 years of age
Measured: At 5.5 years of age
Microbiome composition in stool samples
The relative abundance and diversity of microbial taxa will be analyses with next generation sequencing and be related till the study intervention
Measured: At 1, 2, 3 and 4 weeks of age and gestational week 36+0
Levels of subclasses of T and B cells and granulocytes in blood samples
T helper subsets (TH1, Th2, TH17, Treg), T cells subsets associated with the intestinal mucosa (gamma/delta-T cells, MAIT cells) and neutrophils will be assessed using masscytometry
Measured: At 1, 2 and 4 weeks of age and gestational week 36+0
Levels of immune markers in plasma
Pre planned analyses are anti-inflammatory (e.g. IL-10) and proinflammatory (e.g. TNF) cytokines and chemokines (e.g. CXCL11, CCL18).
Measured: At 1, 2 and 4 weeks of age and gestational week 36+0
Levels of growth factors in plasma samples
The levels of growth factors such as IGF-1 and the associated IGFBP-3 will be analysed.
Measured: At 1, 2 and 4 weeks of age and gestational week 36+0
Levels of lipids in plasma samples
Fatty acids in plasma
Measured: At 1, 2 and 4 weeks of age and gestational week 36+0
Levels of neurotransmitters in plasma samples
Neurotransmitters such as GABA and serotonin in plasma
Measured: At 1, 2 and 4 weeks of age and gestational week 36+0
Levels of metabolic peptides in urine samples
Metabolic peptide will be measured with proton nuclear magnetic resonance spectroscopy (NMR), liquid chromatography (LC) and mass spectroscopy couple to gas chromatography (GC-MC).
Measured: At 1, 2, 3 and 4 weeks of age and gestational week 36+0
Levels of markers of central nervous system (CNS) damage in plasma samples
Markers of CNS damage such as neurofilament light protein will be measured in plasma
Measured: At 1, 2 and 4 weeks of age and gestational week 36+0
Levels of proteins in breast milk samples
Protein composition will be measured with multiplex methods
Measured: At 1, 2, 3 and 4 weeks of age and gestational week 36+0
Levels of human milk oligosaccharides in breast milk samples
The levels of human milk oligosaccharides will be measured with high-performance anion-exchange chromatography with pulsed amperometric detection.
Measured: At 1, 2, 3 and 4 weeks of age and gestational week 36+0
Health care costs
The number of days at each level of care will be recorded until discharge from the hospital (not longer than gestational week 44+0). The cost will be calculated by multiplying the number of days at each level of care by the average cost
Measured: From birth until discharge from hospital (but not loner than gestational week 44+0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2019
- Study start1 Feb 2019
- Primary completion1 Sep 2022
- Study completion31 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Necrotizing EnterocolitisStudies 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 229 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Abrahamsson, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- Sahlgrenska University Hospital, Region Uppsala Public Health and Care, Vasterbottens lans landsting, Prolacta Bioscience, Region Stockholm
- Responsible party
- Sponsor-investigator, Thomas Abrahamsson, MD, PhD, Ostergotland County Council, Sweden
- Investigators
- Thomas R Abrahamsson, MD, PhD, Principal investigator, Region Östergötland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03797157
- Sponsor's protocol ID
- RegionOstergotland
- Acronym
- N-forte
- Status last verified
- Jul 2024
- First submitted
- 17 Dec 2018
- Last updated
- 23 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38545091Jensen 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.
PubMed 34815288
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nordic Study on Human Milk Fortification in Extremely Preterm Infants: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03797157
- Acronym / sponsor ID
- N-forte / RegionOstergotland
- Conditions
- Necrotizing Enterocolitis, Sepsis, Mortality
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 229 participants (actual)
- Lead sponsor
- Thomas Abrahamsson, MD, PhDUniversity, hospital or other
- Collaborators
- Sahlgrenska University Hospital, Region Uppsala Public Health and Care, Vasterbottens lans landsting, Prolacta Bioscience, Region Stockholm
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 1 Sep 2022 (actual)
- Study completion
- 31 Jan 2029 (estimated)
- First posted
- 9 Jan 2019 (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.
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.
Detailed description
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. If fortification with extra enteral lipids is needed during the intervention period, the infants receiving H2MF® will be supplemented with the human milk-based Prolact CR®, while the infants receiving standard bovine protein-based fortification will be supplemented with the standard lipid products used at the unit. The study subject will be enrolled at level III neonatal intensive care unit (NICU)s. Only infants with a home clinic with the logistics to maintain the intervention until gestational week 34+0 will be included.
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. It would not be possible to prescribe the fortifier and prepare of the breast milk in a blinded fashion, since the fortifiers are not exactly equal in nutrient content and also look different. Instead the assessment of several of the outcomes will be made blinded, such as the assessment of X-ray images in NEC cases.
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.
Since it is often difficult to distinguish between the diagnoses of NEC and sepsis, and their clinical consequences, the investigator's primary endpoint of the intervention is the composite variable NEC, sepsis and mortality. Secondary endpoints are feeding intolerance and other severe complication such as Bronchopulmonary dysplasia (BPD), Retinopathy of prematurity (ROP) and neurological impairment. Stool, urine and blood samples are also collected for microbiology, metabolomic and immunology analysis in order to study underlying mechanisms. Health economic analyses will be made to evaluate the costs and benefits of an introduction of human milk-based fortifier in NICUs in the Nordic countries.
Analyses will be conducted using an intention to treat approach. An evaluation will be performed when 20 infants have been included to evaluate feasibility and make it possible to adjust the protocol for the remaining part of the study. Safety analyses will be performed by an independent data and safety monitoring board (DSMB) when 50, 100 and 150 infants have been included. A sample size re-estimation will be made by an independent statistician when 150 infants have been included. Thus, the definitive sample size might be increased (never decreased) based on this interim analysis. The study can be terminated before 322 infants have been enrolled based on a decision of the sponsor and the DSMB, if the primary outcome is significantly lower (with a significance level <0.001) in the H2MF® than in the standard fortification group in the interim analysis made after 150 infants have completed the neonatal period. The study subject will be enrolled at level III NICUs in the Nordic Countries. All study subjects will be followed during the neonatal period until discharge (not longer than gestational week 44+0) and also be included in a follow up at 2 and 5.5 years of age based on the national follow up program for extremely preterm infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| H2MF | Experimental | Dietary Supplement: H2MFHuman milk-based breast milk fortifier |
| Standard fortifier | Active comparator | Dietary Supplement: Bovine milk-based fortifierStandard care: bovine milk-based breast milk fortifier |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- Lethal or complicated malformation known at the time of inclusion
- Chromosomal anomalies known at the time of inclusion
- No realistic hope for survival at the time of inclusion
- Gastrointestinal malformation known at the time of inclusion
- Abdominal surgery before the time of inclusion
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 |
|---|---|---|
| H2MFH2MF is a human milk-based breastmilk fortifier for preterm infants | Dietary supplement | H2MF |
| Bovine milk-based fortifierBovine milk-based fortifier is the standard breast milk fortifier in Sweden | Dietary supplement | Standard fortifier |
Primary outcome
The incidence of the composite of necrotizing enterocolitis, culture-proven sepsis and mortality
Time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)
An infant should have had any of these diagnoses to fulfil the criterion
52 secondary outcomes
The incidence of the composite of necrotizing enterocolitis and culture-proven sepsis
Time frame: 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)
Time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)
Time to reach full enteral feeds
Time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)
Number of feeding interruptions
Time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)
Numbers of days with parenteral nutrition
Time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)
Number of large gastric aspirates per day
Time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)
Stool frequency
Time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)
Time to regain birth weight
Time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)
Change in head circumference in centimeters
Time frame: At 7, 14, 21 and 28 days, the end of intervention (gestational week 34+0), gestational week 36+0, at discharge from neonatal ward (or at gestational week 44+0, whatever comes first) and at 2 years of age (corrected) and 5.5 years of age (uncorrected).
Change in weight in gram
Time frame: At 7, 14, 21 and 28 days, the end of intervention (gestational week 34+0), gestational week 36+0, at discharge from neonatal ward (or at gestational week 44+0, whatever comes first) and at 2 years of age (corrected) and 5.5 years of age (uncorrected).
Change in length in centimeters
Time frame: At 7, 14, 21 and 28 days, the end of intervention (gestational week 34+0), gestational week 36+0, at discharge from neonatal ward (or at gestational week 44+0, whatever comes first) and at 2 years of age (corrected) and 5.5 years of age (uncorrected).
The mortality incidence
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of necrotising enterocolitis: Bell´s stage II-III
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence spontaneous intestinal perforation
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of abdominal surgery
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence culture-proven sepsis
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of suspected sepsis, not culture-proven
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of pneumonia
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of bronchopulmonary dysplasia
Time frame: At gestational week 36+0
The incidence of retinopathy of the prematurity
Time frame: From birth until gestational week 42+0
The incidence of intraventricular haemorrhage
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
The incidence of periventricular leukomalacia
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
Number of days with intensive care
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
Length of stay at the hospital
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
Length of need of feeding tube
Time frame: From birth until discharge from hospital (but not loner than gestational week 44+0)
Neurocognitive development at 2 years
Time frame: At 2 years of age
Prevalence of cerebral palsy at 2 years
Time frame: At 2 years of age
Prevalence of epilepsy at 2 years
Time frame: At 2 years of age
Prevalence of squint and/or impaired vision at 2 years
Time frame: At 2 years of age
Prevalence of impaired hearing at 2 years
Time frame: At 2 years of age
The number of infants needing extra oxygen and/or ventilatory support after discharge from the hospital at the neonatal period
Time frame: From gestational week 44 until 2 years of age
The incidence of wheeze and/or asthma
Time frame: From birth until 2 years of life
The incidence of severe infections after discharge from the neonatal unit
Time frame: From gestational week 44 until 2 years of age
The number of infants needing feeding tube after discharge from the hospital at the neonatal period
Time frame: From gestational week 44 until 2 years of age
The number of infants needing extra nutritional support after discharge from the hospital at the neonatal period
Time frame: From gestational week 44 until 2 years of age
The prevalence of neurocognitive development at 5.5 years
Time frame: At 5.5 years of age
The prevalence of cerebral palsy at 5.5 years
Time frame: At 5.5 years of age
The prevalence of epilepsy at 5.5 years of age
Time frame: At 5.5 years of age
The prevalence of squint and/or impaired vision at 5.5 years of age
Time frame: At 5.5 years of age
The prevalence of children with impaired hearing at 5.5 years of age
Time frame: At 5.5 years of age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2024.
- Derived from this study: PubMed 38545091Jensen 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.
- Derived from this study: PubMed 34815288Jensen 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.
- 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.
Thomas R Abrahamsson, MD, PhD principal investigator
Region Östergötland
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing H2MF and Bovine milk-based fortifier in people with Necrotizing Enterocolitis and Sepsis, run by Thomas Abrahamsson, MD, PhD at 5 sites in Sweden.
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 7 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: under way, not looking for participants, as of the sponsor's last update on 23 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Sweden. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
The incidence of the composite of necrotizing enterocolitis, culture-proven sepsis and mortality (time frame: From birth until discharge from hospital (but not longer than gestational week 44+0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03797157, which also lists 2 linked publications.
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 23 Jul 2024.