Very Low Birth Weight InfantNCT04078906
SMOFlipid and Incidence of BPD in Preterm Infants
A study testing n3-LCPUFA enriched Intravenous Lipid Emulsion in people with Very Low Birth Weight Infant and Bronchopulmonary Dysplasia, run by University of Calgary at 1 site in Canada.
Trial summary
Despite many advances in neonatal care in the recent years, bronchopulmonary dysplasia (BPD) continues to be the major cause of chronic lung morbidity in infants. The pathogenesis of BPD is multifactorial; however, inflammation remains the central pathway for all risk factors. Read more about this study
- Who is it for?
- Ages 1 hour to 48 hours
- Conditions the study is for
- Very Low Birth Weight Infant, Bronchopulmonary Dysplasia
- What is being tested?
- n3-LCPUFA enriched Intravenous Lipid Emulsion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 384 participants
- Where
- 1 siteCanada
- Study dates
- 16 Dec 2019to Oct 2024
- Phase
- Interventional
- 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 1 hour to 48 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm infants born <30 weeks and admitted to NICU at Foothills Medical Centre in the first 24 hours of life.
- Anticipated duration of PN for >7 days
Who cannot join
- Infants with congenital anomalies
- Infants with suspected inborn errors of metabolism or family history of inborn error of metabolism
- Perinatal asphyxia
- Evidence of congenital infection
- Primary biliary atresia
Trial locations and contacts
1 site in 1 country.
Canada1 site, 1 recruiting
- Recruiting
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
Belal Alshaikh, MD, belal.alshaikh@ahs.ca
About this study
Official title: Does Parenteral Omega-3 Enriched Lipid Emulsion Reduce Incidence of Bronchopulmonary Dysplasia in Preterm Infants
Despite many advances in neonatal care in the recent years, bronchopulmonary dysplasia (BPD) continues to be the major cause of chronic lung morbidity in infants. The pathogenesis of BPD is multifactorial; however, inflammation remains the central pathway for all risk factors. Omega-3 long chain polyunsaturated fatty acids (n3-LCPUFAs) from fish oil are known to down-regulate systemic inflammation and oxidative stress. Currently used soybean-based fatty acid emulsion (Intralipid) contains mainly n6-LCPUFA. Intralipid does not maintain the in-utero balanced LCPUFA accretion. Furthermore, Intralipid has been shown to increase free radical production and to be associated with BPD. A new fatty acid emulsion enriched with n3-LCPUFA (SMOFlipid) improves the fatty acid profile and reduces pro-inflammatory agents.
This project aims primarily to study whether SMOFlipid can lower the rate of BPD in preterm infants compared to Intralipid.
Read the detailed description
Intravenous lipid emulsions (IVLEs) is a core component of parenteral nutrition (PN) for providing calories and essential fatty acids. Until recently, Intralipid was the only available IVLE in North America. For a long time now, the use of Intralipid has been described to be associated with the development of BPD. Lack of sufficient lipid clearance in premature infants, augmented oxidative stress, deficiency of anti-inflammatory agents, and elevated pulmonary artery pressure have all shown to be potential causes for lung injury during the use of Intralipid.
Intralipid, made mainly of soybean oil, contains high amounts of n6-LCPUFA and low amounts of n3-LCPUFA. This results in prostaglandin synthesis favoring pro-inflammatory products and amplified oxidative stress. Current evidence indicates that well-balanced fatty acid supply is a crucial factor to reduce inflammation and oxidative stress. The concern about unbalanced n6:n3 ratio has led to the development of novel IVLEs, like SMOFlipid. SMOFlipid is composed of a mixture of soybean oil (30%), medium-chain triglycerides (MCT) (30%), olive oil (25%) and fish oil (15%). The combination of soybean oil and fish oil allows delivering balanced LCPUFA with n6:n3 ratio of 2.5:1 and provides sufficient amounts of the preformed n3-LCPUFA.
Interventions that improve n3-LCPUFA status have been shown to reduce pulmonary inflammation in animal models.
In humans, a study on extremely preterm infants has revealed a rapid decline in the n3-LCPUFA in the first week of life despite the use of Intralipid. Early restoration of an adequate ratio of LCPUFA to inhibit inflammation has gained interest in recent years. In an observational study by Skouroliakou et al., very low birth weight infants receiving SMOFlipid within 48 hours of birth and for at least 7 days had a lower incidence of BPD compared to the Intralipid control group. A recent systematic review and meta-analysis of 8 randomized control trials (7 compared SMOFlipid to Intralipid) was conducted to evaluate safety and efficacy of fish oil-enriched IVLEs in preterm infants. Infants who received fish oil-enriched IVLEs had significantly higher RBC membrane DHA and EPA. The meta-analysis showed no difference in all-cause mortality and overall complication rate in 238 infants receiving fish oil-enriched IVLEs. However, all the studies included in this meta-analysis were small. Furthermore, the studies focused mainly on laboratory findings, and did not aim to study effect on inflammation, oxidative stress or clinical outcomes. Studies from critically ill adults in intensive care units exhibited a reduction in the duration of hospitalization and ventilator days, a risk factor for lung injury, when using n3-LCPUFA enriched IVLEs.
- Being tested
- n3-LCPUFA enriched Intravenous Lipid Emulsion
- Keywords
- Intravenous lipid emulsions, SMOF, Preterm Infants
- Medical subject headings
- Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
n3-LCPUFA enriched Intravenous Lipid EmulsionOther
Also called SMOFlipid
To start from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day.
| Study group | Role | What they receive |
|---|---|---|
| Control group | No intervention | Conventional IVLE (Intralipid) from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day. |
| Experimental group | Experimental | n3-LCPUFA enriched IVLE (SMOFlipid) from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day. Receives: Other: n3-LCPUFA enriched Intravenous Lipid Emulsion |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of Bronchopulmonary Disease
According to Child Health and Human Development with classification to mild, moderate and severe.
Measured: 36 weeks corrected gestational age
Fatty acid profile
Determine serum fatty acids levels (μmol/L).
Measured: First 3 weeks of life
Pro-inflammatory cytokine response
Compare pro-inflammatory cytokine levels (pg/mL)
Measured: First 3 weeks of life
Lipid peroxidation measure 1
Malondialdehyde (MDA, μmol/L) in blood
Measured: First 3 weeks of life
Lipid peroxidation measure 2
8-isoprostane levels (pg/mL) in blood
Measured: First 3 weeks of life
Secondary outcomes (5)
Incidence of Cholestasis
Direct bilirubin more than 34 mmol/L
Measured: Up to 36 weeks corrected gestational age or discharge
Weight gain velocity
Change in weight Z scores
Measured: Up to 36 weeks corrected gestational age or discharge
Incidence of retinopathy of prematurity
Defined as stage 2 or higher according to the international classification or requiring treatment.
Measured: Up to 36 weeks corrected gestational age or discharge
Incidence of moderate to severe neurodevelopmental disability
Defined by 1 or more of the following: moderate to severe motor impairment cerebral palsy (CP) or non-CP) with a GMFCS level ≥2, a BSID III cognitive score of <70, severe visual impairment (bilateral blindness with vision <20/200), or severe hearing impairment (permanent hearing loss that interferes with ability to understand or communicate with or without amplification).
Measured: 18-22 months corrected gestational
Incidence of severe intraventricular hemorrhage (IVH)
Defined as grade 3 or higher
Measured: Up to 36 weeks corrected gestational age or discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2019
- Study start16 Dec 2019
- Primary completionOct 2024 (estimated)
- Study completionOct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Very Low Birth Weight InfantStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 384 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Belal Alshaikh, University of Calgary
- Investigators
- Belal Alshaikh, MD, MSc, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04078906
- Sponsor's protocol ID
- REB19-1088
- Status last verified
- Nov 2022
- First submitted
- 27 Aug 2019
- Last updated
- 7 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- 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 7 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Parenteral Omega-3 Enriched Lipid Emulsion Reduce Incidence of Bronchopulmonary Dysplasia in Preterm Infants
- ClinicalTrials.gov ID
- NCT04078906
- Acronym / sponsor ID
- REB19-1088
- Keywords
- Intravenous lipid emulsions, SMOF, Preterm Infants
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 384 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 16 Dec 2019 (actual)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Oct 2024 (estimated)
- First posted
- 6 Sep 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.
Despite many advances in neonatal care in the recent years, bronchopulmonary dysplasia (BPD) continues to be the major cause of chronic lung morbidity in infants. The pathogenesis of BPD is multifactorial; however, inflammation remains the central pathway for all risk factors. Omega-3 long chain polyunsaturated fatty acids (n3-LCPUFAs) from fish oil are known to down-regulate systemic inflammation and oxidative stress. Currently used soybean-based fatty acid emulsion (Intralipid) contains mainly n6-LCPUFA. Intralipid does not maintain the in-utero balanced LCPUFA accretion. Furthermore, Intralipid has been shown to increase free radical production and to be associated with BPD. A new fatty acid emulsion enriched with n3-LCPUFA (SMOFlipid) improves the fatty acid profile and reduces pro-inflammatory agents.
This project aims primarily to study whether SMOFlipid can lower the rate of BPD in preterm infants compared to Intralipid.
Detailed description
Intravenous lipid emulsions (IVLEs) is a core component of parenteral nutrition (PN) for providing calories and essential fatty acids. Until recently, Intralipid was the only available IVLE in North America. For a long time now, the use of Intralipid has been described to be associated with the development of BPD. Lack of sufficient lipid clearance in premature infants, augmented oxidative stress, deficiency of anti-inflammatory agents, and elevated pulmonary artery pressure have all shown to be potential causes for lung injury during the use of Intralipid.
Intralipid, made mainly of soybean oil, contains high amounts of n6-LCPUFA and low amounts of n3-LCPUFA. This results in prostaglandin synthesis favoring pro-inflammatory products and amplified oxidative stress. Current evidence indicates that well-balanced fatty acid supply is a crucial factor to reduce inflammation and oxidative stress. The concern about unbalanced n6:n3 ratio has led to the development of novel IVLEs, like SMOFlipid. SMOFlipid is composed of a mixture of soybean oil (30%), medium-chain triglycerides (MCT) (30%), olive oil (25%) and fish oil (15%). The combination of soybean oil and fish oil allows delivering balanced LCPUFA with n6:n3 ratio of 2.5:1 and provides sufficient amounts of the preformed n3-LCPUFA.
Interventions that improve n3-LCPUFA status have been shown to reduce pulmonary inflammation in animal models.
In humans, a study on extremely preterm infants has revealed a rapid decline in the n3-LCPUFA in the first week of life despite the use of Intralipid. Early restoration of an adequate ratio of LCPUFA to inhibit inflammation has gained interest in recent years. In an observational study by Skouroliakou et al., very low birth weight infants receiving SMOFlipid within 48 hours of birth and for at least 7 days had a lower incidence of BPD compared to the Intralipid control group. A recent systematic review and meta-analysis of 8 randomized control trials (7 compared SMOFlipid to Intralipid) was conducted to evaluate safety and efficacy of fish oil-enriched IVLEs in preterm infants. Infants who received fish oil-enriched IVLEs had significantly higher RBC membrane DHA and EPA. The meta-analysis showed no difference in all-cause mortality and overall complication rate in 238 infants receiving fish oil-enriched IVLEs. However, all the studies included in this meta-analysis were small. Furthermore, the studies focused mainly on laboratory findings, and did not aim to study effect on inflammation, oxidative stress or clinical outcomes. Studies from critically ill adults in intensive care units exhibited a reduction in the duration of hospitalization and ventilator days, a risk factor for lung injury, when using n3-LCPUFA enriched IVLEs.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | No intervention | –Conventional IVLE (Intralipid) from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day. |
| Experimental group | Experimental | Other: n3-LCPUFA enriched Intravenous Lipid Emulsionn3-LCPUFA enriched IVLE (SMOFlipid) from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day. |
Who may qualify
- Ages
- 1 hour to 48 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Preterm infants born <30 weeks and admitted to NICU at Foothills Medical Centre in the first 24 hours of life.
- Anticipated duration of PN for >7 days
Key exclusion criteria (5 listed)
- Infants with congenital anomalies
- Infants with suspected inborn errors of metabolism or family history of inborn error of metabolism
- Perinatal asphyxia
- Evidence of congenital infection
- Primary biliary atresia
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 |
|---|---|---|
| n3-LCPUFA enriched Intravenous Lipid EmulsionAlso: SMOFlipidTo start from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day. | Other | Experimental group |
Primary outcome
The incidence of Bronchopulmonary Disease
Time frame: 36 weeks corrected gestational age
According to Child Health and Human Development with classification to mild, moderate and severe.
Fatty acid profile
Time frame: First 3 weeks of life
Determine serum fatty acids levels (μmol/L).
Pro-inflammatory cytokine response
Time frame: First 3 weeks of life
Compare pro-inflammatory cytokine levels (pg/mL)
Lipid peroxidation measure 1
Time frame: First 3 weeks of life
Malondialdehyde (MDA, μmol/L) in blood
Lipid peroxidation measure 2
Time frame: First 3 weeks of life
8-isoprostane levels (pg/mL) in blood
5 secondary outcomes
Incidence of Cholestasis
Time frame: Up to 36 weeks corrected gestational age or discharge
Weight gain velocity
Time frame: Up to 36 weeks corrected gestational age or discharge
Incidence of retinopathy of prematurity
Time frame: Up to 36 weeks corrected gestational age or discharge
Incidence of moderate to severe neurodevelopmental disability
Time frame: 18-22 months corrected gestational
Incidence of severe intraventricular hemorrhage (IVH)
Time frame: Up to 36 weeks corrected gestational age or discharge
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2022.
- Individual participant dataSharing planned: No
Related trials for Very Low Birth Weight Infant
Recruiting
Effect of Developmental Care on Very Low Birth Weight Infants
Intervention
Active, not recruiting
30% or 60% Oxygen at Birth to Improve Neurodevelopmental Outcomes in Very Low Birthweight Infants
Premature Infant, Respiratory Distress Syndrome in Premature Infant
RecruitingPhase 1
Gut Permeability and Microbiome in Preterm Infants
Prematurity Complications
Not yet recruitingObservational study
Predictors of Postnatal Growth Failure in Preterm Infants
Premature Birth, Growth Failure
Recruiting
Donor Breast Milk 2
Iron Deficiency Anemia
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.
Belal Alshaikh, MD, MSc principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing n3-LCPUFA enriched Intravenous Lipid Emulsion in people with Very Low Birth Weight Infant and Bronchopulmonary Dysplasia, run by University of Calgary at 1 site in Canada.
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 2 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 7 Nov 2022. 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 Canada. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Belal Alshaikh, MD, MSc ((403) 956 1588, belal.alshaikh@ahs.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of Bronchopulmonary Disease (time frame: 36 weeks corrected gestational age). The study lists 5 primary outcomes in all. 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 7 Nov 2022.