Omegaven as Alternative Parenteral Fat Nutrition

An intermediate population, Investigational New Drug study, to provide an alternate intravenous fat nutrition, Omegaven®, to help improve liver function while providing adequate nutrition for critically ill infants with parenteral nutrition associated cholestasis

• Omegaven (Drug): Omegaven® fat emulsion will be used as a compassionate use treatment for critically ill infants with parenteral nutrition associated liver injury

Primary outcomes

• Number of Participant With Decrease in Direct Bilirubin Level [First month of treatment]: Number of participant with decrease in direct bilirubin levels within 30 days of treatment

Secondary outcomes

• Number of Participant With Resolution of Direct Hyperbilirubinemia [2 months]: Number of participant with Direct bilirubin level of <2mg/dL at discontinuation of treatment
• Number of Participant With Preservation of Length [Weekly measurement during treatment. Evaluation every 30 days from treatment initiation until discontinuation of treatment, patient hospital discharge, whichever comes first, or up to 6 months following initiation of treatment]: Monitoring of weekly length while the patient is receiving Omegaven® treatment
• Number of Participant With Preservation of Head Circumference [Weekly measurement during treatment. Evaluation every 30 days from treatment initiation until discontinuation of treatment, patient hospital discharge, whichever comes first, or up to 6 months following initiation of treatment]: Monitoring of weekly head circumference while the patient is receiving Omegaven® treatment
• Number of Participant With Preservation of Normal Weight Gain [Weekly measurement during treatment. Evaluation every 30 days from treatment initiation until discontinuation of treatment, patient hospital discharge, whichever comes first, or up to 6 months following initiation of treatment]: Monitoring of daily weight gain while the patient is on Omegaven®

Sex: All, ages: 14 Days to any

Inclusion Criteria:

* Greater than 14 days old
* Has parenteral nutrition associated cholestasis defined as at least 2 consecutive direct bilirubin >2 mg/dL with anatomical or functional short gut (OR >4 mg/dL if intact intestine) obtained at least 1 week apart with a ratio of direct: total bilirubin > 0.4
* Patient is parenteral nutrition dependent (unable to meet nutritional needs solely by enteral nutrition) and are expected to require parenteral nutrition for at least 3 more weeks
* Patient has not responded to other therapeutic approaches for parenteral nutrition-associated liver disease such as : cycling of parenteral nutrition, avoiding overfeeding, reduction/removal of copper and manganese from parenteral nutrition, advancement of enteral feeding, and use of Ursodiol
* Patient has been on at least 2 weeks of SMOFLIPIDs with no improvement or worsening of direct bilirubin levels
* Signed patient informed consent
* The patient is expected to have a reasonable possibility of survival
* No other known etiology of cholestasis other than parenteral nutrition-associated liver disease at the time of Omegaven® initiation

Exclusion Criteria:

* Known causes of cholestasis other than parenteral nutrition-associated liver disease including but not limited to Hepatitis C, Cystic fibrosis, biliary atresia, and alpha 1 antitrypsin deficiency are present, prior to Omegaven® initiation
* Known fish or egg allergy
* Any of the contraindications to use of Omegaven®:

  1. Active new infection at the time of initiation of Omegaven®
  2. Hemodynamic instability
  3. Recent use of medications with associated risk of bleeding, including NSAIDs
  4. Active coagulopathy or bleeding
  5. Platelet counts persistently under 30,000 despite transfusions
  6. Unstable hyperglycemia
  7. Impaired lipid metabolism (triglycerides >1000 mg/dL) while on 1 g/kg/day or less of Intralipid
  8. History of severe hemorrhagic disorders (ie. hemophilia, Von Willebrand disease, etc.)
  9. Unstable diabetes mellitus
  10. Collapse and shock
  11. Stroke/ Embolism
  12. Cardiac infarction within the last 3 months
  13. Undefined coma status

Participant flow

Outcome results

• Number of Participant With Decrease in Direct Bilirubin Level (Primary), Count of participants, Participants: Drug - Omegaven® 2
• Number of Participant With Resolution of Direct Hyperbilirubinemia (Secondary), Count of participants, Participants: Drug - Omegaven® 1
• Number of Participant With Preservation of Length (Secondary), Count of participants, Participants: Drug - Omegaven® 2
• Number of Participant With Preservation of Head Circumference (Secondary), Count of participants, Participants: Drug - Omegaven® 2
• Number of Participant With Preservation of Normal Weight Gain (Secondary), Count of participants, Participants: Drug - Omegaven® 2

Adverse events

Time frame: 2 months

• Study Protocol (PDF, 2018-05-01)

• Thao Ho, DO, Principal investigator, University of South Florida