Omegaven as Alternative Parenteral Fat Nutrition

Phase 3

Completed

Brief Summary: To provide Omegaven® as a compassionate treatment for critically ill infants with parenteral nutrition associated cholestasis

Detailed Description: 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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Drug - Omegaven®	Omegaven	Therapy with Omegaven® will be initiated at the goal dose of 0.5-1/kg/day. The default is over 24 hours, but shorter intervals may be considered if a program of total parenteral nutrition cycling is recommended. Omegaven® will be infused intravenously through either a central or peripheral catheter.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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®