Omegaven (omega-3 long-chain polyunsaturated fatty acids) / Fresenius Kabi - LARVOL DELTA

Displacement of Bilirubin from Albumin by Omegaven and Intralipid. (PubMed, J Pediatr Surg) - "Omegaven-derived FFAu displaced less bilirubin from albumin than Intralipid-derived FFAu, indicating its potential neuroprotective as well as hepatoprotective advantages."

Journal

Assessment of the association between mixed-oil lipid injectable emulsion use and 30-day mortality or infection persistence from fungal catheter-related bloodstream infections in pediatric patients following receipt of parenteral nutrition: A retrospective cohort study. (PubMed, Pharmacotherapy) - "Use of mixed-oil lipid injectable emulsion compared to other formulations (soybean-oil or fish-oil) demonstrated a non-statistically significant increase in 30-day mortality and/or infection persistence from fungal catheter-related bloodstream infections in pediatric patients receiving parenteral nutrition."

Journal • Retrospective data • Infectious Disease • Pediatrics

MODIFYCSX: Intravenous Fish Oil Based Lipid Emulsion to Enhance Recovery in High-Risk Cardiac Surgery Patients (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: GCP-Service International West GmbH | Trial completion date: Dec 2025 ➔ Feb 2027 | Trial primary completion date: Dec 2024 ➔ Feb 2026

Trial completion date • Trial primary completion date • Cardiovascular • Critical care

Safety Study to Evaluate the Occurrence of EFAD in Pediatric Patients With PNAC Who Require More Than Eight Weeks of Omegaven Treatment (clinicaltrials.gov) - P=N/A | N=40 | Recruiting | Sponsor: Fresenius Kabi | Not yet recruiting ➔ Recruiting | Initiation date: May 2024 ➔ Dec 2024

Enrollment open • Trial initiation date • Cholestasis • Hepatology • Pediatrics

Intestinal failure-associated liver disease model: a reduced phytosterol intravenous lipid emulsion prevents liver injury. (PubMed, Pediatr Res) - "Half of children receiving long-term parenteral nutrition develop intestinal failure-associated liver disease (IFALD). Standard intravenous lipid emulsions (ILEs) in parenteral nutrition are vegetable oil based and high in phytosterols (plant steroids); no low phytosterol vegetable oil-based ILE is available. Phytosterols in ILEs are associated with IFALD. In this study, a new phytosterol-depleted soybean oil was utilized in a laboratory-generated ILE. Use of the phytosterol-depleted soybean oil ILE prevented liver injury in a murine model of IFALD. Phytosterol-depleted soybean oil may be utilized as a component of less toxic next-generation ILEs."

Journal • Hepatology • Inflammation • Liver Failure

Impact of Omega-3 Fatty Acid Supplementation in Parenteral Nutrition on Inflammatory Markers and Clinical Outcomes in Critically Ill COVID-19 Patients: A Randomized Controlled Trial. (PubMed, Nutrients) - "A total of 69 patients were randomized into three groups: one received standard lipid emulsion, and two received O3FA (Omegaven®) at doses of 0.1 g/kg/day and 0.2 g/kg/day, respectively, in addition to Smoflipid®...Additionally, the higher O3FA dose was associated with a shorter ICU and hospital stay. These findings suggest that O3FA supplementation in PN may reduce inflammation and improve clinical outcomes in critically ill COVID-19 patients."

Biomarker • Clinical • Clinical data • Journal • Critical care • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CRP • CXCL10 • IFNG • IL1R1 • IL6 • TNFA

Cholestasis Reversal: Efficacy of IV Fish Oil (clinicaltrials.gov) - P2/3 | N=91 | Completed | Sponsor: Mark Puder | N=290 ➔ 91

Enrollment change • Cholestasis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Short Bowel Syndrome

Omegaven is not cytoprotective after Inflammation-Amplified Hypoxia-Ischemia in a Newborn Piglet Model (PAS 2024) - "Insult severity was no different between groups. Significantly higher Triglyceride levels were observed in the Omegaven group at 65h (p=0.002). No significant group differences in other markers of liver function or physiological parameters were observed."

Cardiovascular • CNS Disorders • Infectious Disease • Inflammation

High Dose Fish Oil Added to Various Lipid Emulsions Normalizes Superoxide Dismutase 1 Activity in Home Parenteral Nutrition Patients. (PubMed, Nutrients) - "(4) An escalated dose of FO normalized SOD1 activity in HPNPs toward that of HCs. Bile acid metabolism was altered in HPNPs without signs of significant cholestasis and not affected by Omegaven."

Journal • Cholestasis • Dyslipidemia • Gastrointestinal Disorder • Hepatology • Short Bowel Syndrome • FGF19 • PON1 • SOD1

MODIFYCSX: Intravenous Fish Oil Based Lipid Emulsion to Enhance Recovery in High-Risk Cardiac Surgery Patients. (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: GCP-Service International West GmbH

New P2 trial • Cardiovascular • Critical care • IL6

Safety Study to Evaluate the Occurrence of EFAD in Pediatric Patients With PNAC Who Require More Than Eight Weeks of Omegaven Treatment (clinicaltrials.gov) - P4 | N=40 | Not yet recruiting | Sponsor: Fresenius Kabi

New P4 trial • Cholestasis • Hepatology • Pediatrics

Refractory Coagulopathy Associated With Omegaven in an Infant (SCCM 2024) - "This case highlights the potential for coagulopathy resulting from use of Omegaven above the recommended dosing. Further delineation of the mechanism by which Vitamin K factors become deficient is warranted."

Gastrointestinal Disorder • Hematological Disorders • Hepatology • Respiratory Diseases

Crosstalk within peripheral blood mononuclear cells mediates anti-inflammatory effects of n-3 PUFA-rich lipid emulsions in parenteral nutrition. (PubMed, Clin Nutr) - "These results show a mechanism for the beneficial effect of the n-3-rich Omegaven in patients with inflammatory conditions but questions its use in patients with cancer. Hence, our results may assist in choosing the best lipid emulsion for patients who require PN."

Journal • Colorectal Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Solid Tumor • AVEN • CD14 • CD1D • CD8 • CD86 • FOXP3 • IFNG • IL10 • IL4 • TNFA

Safety and Tolerability of Intravenous Fish Oil Lipid Emulsion in Children Undergoing Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Alexandra N. Carey | Active, not recruiting ➔ Completed | Trial completion date: Oct 2023 ➔ May 2023

Trial completion • Trial completion date • Bone Marrow Transplantation • Hematological Malignancies • Myelodysplastic Syndrome • Transplantation • HLA-B • HLA-C • HLA-DRB1

Safety and Tolerability of Intravenous Fish Oil Lipid Emulsion in Children Undergoing Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Alexandra N. Carey | Trial completion date: Jun 2023 ➔ Oct 2023

Trial completion date • Bone Marrow Transplantation • Hematological Malignancies • Myelodysplastic Syndrome • Transplantation • HLA-B • HLA-C • HLA-DRB1

Comparing the efficacy in reducing brain injury of different neuroprotective agents following neonatal hypoxia-ischemia in newborn rats: a multi-drug randomized controlled screening trial. (PubMed, Sci Rep) - "The probability of efficacy was superior to that of HT for Caffeine, SAG, Allopurinol, Melatonin, Clemastine, ß-hydroxybutyrate, and Omegaven. We provide the results of the first systematic preclinical screening of potential neuroprotective treatments and present alternative single therapies that may be promising treatment options for HT in LMIC."

Journal • Preclinical • Cardiovascular • CNS Disorders • Vascular Neurology

Comparing the potency of different neuroprotective agents following neonatal hypoxic-ischemic brain injury in newborn rats – a multi-drug randomized controlled screening trial (PAS 2023) - "In total, 20 animal experiments were performed. Eight of the 26 therapeutic agents significantly reduced brain area loss with the strongest treatment effect for Caffeine, Sonic Hedgehog Agonist (SAG) and Allopurinol, followed by Melatonin, Clemastine, ß-Hydroxybutyrate, Omegaven, and Iodide. The probability of efficacy was superior to HT for Caffeine, SAG, Allopurinol, Melatonin, Clemastine, ß-Hydroxybutyrate, and Omegaven."

Preclinical • CNS Disorders • Vascular Neurology

Safety and Tolerability of Intravenous Fish Oil Lipid Emulsion in Children Undergoing Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Alexandra N. Carey | Recruiting ➔ Active, not recruiting

Enrollment closed • Bone Marrow Transplantation • Hematological Malignancies • Myelodysplastic Syndrome • Transplantation • HLA-B • HLA-C • HLA-DRB1

The use of Omegaven rescue therapy (ORT) in the treatment of Intestinal Failure associated liver disease (IFALD) in patients already received SMOF lipid: a tertiary single centre experience. (BSPGHAN 2023) - "Barclay AR, Henderson P. J Pediatr Gastroenterol Nutr 2016;62(3):363-4 2. ESPGHAN; Lapillonme A et al Clin Nutr 2018;37:2324-36 Figure 1: Tbil levels in 15 patients prior to and after initiating ORT (Median in bold)"

Clinical • Cholestasis • Hepatology • Infectious Disease • Liver Failure • Pediatrics • Septic Shock

Exclusive Fish Oil Lipid Emulsion Rescue Strategy Improves Cholestasis in Neonates on Partially Fish Oil-Based Lipid Emulsion: A Pilot Study. (PubMed, Nutrients) - "This observational pilot study reports data regarding the use of Omegaven™ after the diagnosis of cholestasis while receiving SMOFlipid™...Nine of the neonates died. In conclusion, the use of a 100% fish oil-based emulsion in neonates afflicted with cholestasis developed while on a partially fish oil-based emulsion is associated with a bilirubin decrease."

Journal • Cholestasis • Hepatology

Effects of lipemia on capillary serum protein electrophoresis in native ultra-lipemic material and intravenous lipid emulsion added sera. (PubMed, Clin Chem Lab Med) - "It is vital to use NULM instead of IVLE solutions in lipemia interference studies for all laboratory tests, including CZE SPEP. The fractions concentration values calculated with the total protein concentration should be used for evaluating SPEP results."

Journal

Safety of Omegaven in Pediatric Patients With Parenteral Nutrition-Associated Cholestasis (PNAC) (clinicaltrials.gov) - P=N/A | N=0 | Withdrawn | Sponsor: Fresenius Kabi | N=40 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Cholestasis • Hepatology • Pediatrics

Endothelial Barrier Disruption by Lipid Emulsions Containing a High Amount of N3 Fatty Acids (Omegaven) but Not N6 Fatty Acids (Intralipid). (PubMed, Cells) - "Interestingly, the study's findings contradict previous studies and revealed that Omegaven at high concentration, but not Intralipid, induces cell detachments, impairing endothelial cells' barrier function. In summary, our studies shed new light on the effect of lipid emulsions on the endothelium."

Journal • CDH5

Protective effects of omega-3 fatty acids in a blood-brain barrier-on-chip model and on postoperative delirium-like behaviour in mice. (PubMed, Br J Anaesth) - "We present a new approach to study neuroimmune interactions relevant to perioperative recovery using a microphysiological BBB platform. Changes in barrier function, including dysregulation of pericytes and perivascular macrophages, provide new targets to reduce postoperative delirium."

Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Orthopedics • IL1B • VCAM1

Safety and Tolerability of Intravenous Fish Oil Lipid Emulsion in Children Undergoing Hematopoietic Cell Transplantation (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Alexandra N. Carey | Trial completion date: Jun 2022 ➔ Jun 2023 | Trial primary completion date: Mar 2022 ➔ Mar 2023

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Malignancies • Myelodysplastic Syndrome • Transplantation • HLA-B • HLA-C • HLA-DRB1