O1034: Randomized Controlled Trial Evaluating the Safety and Efficacy of Smoflipid vs Intralipid in Hospitalized Neonates and Infants

Background: Novel lipid products have been introduced to decrease exposure to omega-6 fatty acids and increase omega-3 fatty acids intake. The most widely used novel product containing omega-3 and omega-6 fatty acids is SMOFlipid. This product contains limited omega-6 while providing omega-3, medium chain triglycerides, and omega-9 fatty acids. The primary objective of this study was to evaluate the safety and efficacy of SMOFlipid compared to Intralipid by measuring the number of study patients in each treatment group with conjugated bilirubin > 2 mg/dL during the first 28 days of study treatment (after at least 14 days), confirmed by a second sample 7 days after the first sample. Secondary objectives were comparing efficacy of SMOFlipid to Intralipid in anthropometry, time to full feeds, and overall safety.

Methods: This was a prospective, randomized, controlled, double-blind, parallel-group, Phase 3 multicenter study in 14 study sites in the United States. Patients were randomized in a 1:1 ratio to receive either SMOFlipid or Intralipid. Randomization was stratified depending on the presence of an underlying disease necrotizing enterocolitis (NEC), and no NEC. Infants enrolled had postmenstrual age ≥ 24 weeks; birth weight ≥ 750 g, and a high-risk condition for long-term PN - gastroschisis, duodenal, jejunal or ileal atresia, volvulus, spontaneous intestinal perforation, or NEC (Bell’s stage 2B or higher). At least 80% of baseline nutritional needs were from PN.

Results: SMOFlipid was received by 83 patient and Intralipid by 78 patients. About 40% (33 patients in each group) completed the initial phase of the study, (28 days) on treatment. Demographic data and baseline characteristics were comparable between groups. The risk ratio of 0.59 (95% CI: 0.09, 3.76) indicates that patients receiving SMOFlipid had a 41% reduction in the risk of having conjugated bilirubin values > 2 mg/dL compared to Intralipid during the first 28 days of study treatment. The number of patients with conjugated bilirubin values > 2 mg/dL confirmed by a second sample did not increase after 28 days in the SMOFlipid group while the number in the Intralipid group increased to 9 (Figure). There was no evidence of essential fatty acid deficiency in subjects in the SMOF group after treatment and increased DHA levels were seen in SMOF vs Intralipid patients (Table). Arachidonic Acid levels remained within the reference ranges in both groups (Mayo Clinic neonatal reference ranges used for values).

Conclusion: We found evidence of a trend towards lower rates of elevated conjugated bilirubin in high risk infants treated with SMOFlipid compared to Intralipid although it did not reach statistical significance. No evidence of safety risk was seen related to the use of SMOFlipid. Study conclusions were limited by the overall low rate of cholestasis.