SMOFlipid and Incidence of BPD in Preterm Infants

NCT ID: NCT04078906

Last Updated: 2022-11-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 384 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-16
• Study Completion Date: 2024-10-31

Brief 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. 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.

Conditions

Very Low Birth Weight Infant; Bronchopulmonary Dysplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Control group

Conventional IVLE (Intralipid) from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Experimental group

n3-LCPUFA enriched IVLE (SMOFlipid) from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day.

Group Type: EXPERIMENTAL

n3-LCPUFA enriched Intravenous Lipid Emulsion

Intervention Type: OTHER

To start from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day.

Interventions

n3-LCPUFA enriched Intravenous Lipid Emulsion

To start from D0 at 1g/kg/day and increase by 1 g/kg daily till reaching 3 g/kg/day.

Intervention Type: OTHER

Other Intervention Names

SMOFlipid

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 48 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Belal Alshaikh

Clinical Associate Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Belal Alshaikh, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Foothills Medical Centre

Calgary, Alberta, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Belal Alshaikh, MD, MSc

Role: CONTACT

belal.alshaikh@ahs.ca

(403) 956 1588

Facility Contacts

Belal Alshaikh, MD

Role: primary

belal.alshaikh@ahs.ca

Other Identifiers

REB19-1088

Identifier Type: -

Identifier Source: org_study_id