SMOFlipidÂ®, a composite parenteral nutrition lipid emulsion, prevents progression of Intestinal Failure Associated Liver Disease in infants. A pilot randomized controlled trial.
Ivan Diamond1, Paul Pencharz1, Brian Feldman1, Simon Ling1, Aideen Moore1, Robert Grant1, Nicole de Silva1, Yaron Avitzur1, Peter Fitzgerald2, David Sigalet3, Bryan Dicken4, Justine Turner4, Valerie Marchand5, Paul Wales1
1Group for Improvement of Intestinal Function and Treatment, The Hospital for Sick Children, Toronto, ON, Canada; 2McMaster Children's Hospital, Hamilton, ON, Canada; 3Alberta Children's Hospital, Calgary, AB, Canada; 4Stollery Children's Hospital, Edmonton, AB, Canada; 5CHU Sainte-Justine , Montreal, QC, Canada
Objective : To examine whether SMOFlipid® (Fresenius Kabi, Bad Homburg, Germany) prevents progression of Intestinal Failure Associated Liver Disease (IFALD) in parenteral nutrition (PN) dependent infants with intestinal failure and early hepatic dysfunction. (Conjugated bilirubin 17 – 50 umol/L, 1- 3 mg/dl).
Study Design : Multicenter pilot blinded randomized controlled trial (Clinicaltrials.gov - Registration #: NCT00793195) comparing SMOFlipid® to Intralipid®. PN formulation, including the dose of lipid, was based on the degree enteral tolerance, but was 2-3 g/kg for children receiving >50% of their calories by PN. Subjects received trial lipid for up to 12 weeks, unless they achieved full enteral tolerance sooner. The primary clinical outcome was the serum conjugated bilirubin at the time of trial completion. Analysis was by intention to treat.
Results : Twenty-four infants (mean age: 6 weeks) participated in the trial – 13 Intralipid®and 11 SMOFlipid®. At the time of trial enrolment subjects in both groups were receiving 90% of their calories by PN. Mean duration on trial was 8 weeks, which did not differ according to treatment (p = 0.99). At trial conclusion, subjects who received SMOFlipid® had a lower conjugated bilirubin than those who received Intralipid® (- 59 umol/L; 95% Confidence Interval: -111 to -7, p = 0.03). Subjects receiving SMOFlipid®were also more likely to have a decrease in serum conjugated bilirubin to 0 umol/l than those in the Intralipid group over the entire observation period (Hazard Ratio = 10.6, 95% Confidence Interval: 1.3 to 8.9, p = 0.03). Time to achievement of full enteral tolerance did not differ statistically (Hazard Ratio = 1.4, 95% CI: 0.5 to 3.8, p = 0.49) between the groups. There was no significant difference in safety outcomes between the groups.
Conclusion : Compared with Intralipid®, SMOFlipid® reduces the risk of progressive IFALD in children with intestinal failure and early hepatic dysfunction.