Cholestasis, Total Parenteral Nutrition-induced Cholestasis
Conditions
Keywords
Cholestasis, Parenteral Nutrition Associated Liver Disease
Brief summary
This is a compassionate use protocol to use intravenous fish oil infusion, Omegaven®, to infants and children with parenteral nutrition-associated liver disease to enable reversal of elevated serum liver enzymes and direct bilirubin (cholestasis).
Detailed description
Intravenous lipids are necessary in PN (parenteral nutrition) dependent patients due to their high caloric value and essential fatty acid content. However, parenteral fat emulsions composed of soybean oils (omega 6 fatty acids) have been implicated in predisposing patients to PN associated liver disease. It is hypothesized that by administering Omegaven®, comprised of fish oil (omega 3 fatty acids) in place of conventional soybean fat emulsion, the progression of PN-associated cholestasis may be prevented or reversed.
Interventions
DRUGOmegaven
Omegaven® will be initiated at a dose of 0.5 gram/kg/day and is infused over 24 hours for 1-2 days, and then advanced to 1 gram/kg/day. Omegaven® will be infused intravenously through either a central or peripheral catheter alone or in conjunction with parenteral nutrition. Omegaven® will continue until weaned from PN. Monotherapy with Omegaven® can continue as an additional source of calories after the dextrose/protein portion of PN is discontinued. Omegaven may be restarted within seven days of discontinuing therapy. After seven days, and meeting inclusion criteria, Omegaven can resume at the initial dose of 0.5 grams/kg/day, advancing to 1 gm/kg/day.
Sponsors
Cindy Haller
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Weeks to 5 Years
Healthy volunteers
No
Inclusion criteria
* Two consecutive direct bilirubin levels of 2 mg/dl or more in a parenteral nutrition dependent infant or child (unable to meet nutritional needs solely by enteral nutrition) * Other causes of liver disease have been excluded. A liver biopsy is not necessary for treatment. * The patient must have utilized standard therapies to prevent the progression of the liver disease including reduction/removal of copper and manganese from daily PN, trial of enteral feeding if possible, and the use of ursodiol (i.e., Actigall®).
Exclusion criteria
* Documented causes of chronic liver disease other than parenteral nutrition associated liver disease * Proven severe advanced liver disease including cirrhosis on biopsy, varices, ascites. * An allergy to any seafood product, egg protein, and/or previous allergy to Omegaven® * Active coagulopathy characterized by ongoing bleeding or by a requirement for clotting factor replacement (e.g. fresh frozen plasma or cryoprecipitate) to maintain homeostasis * Impaired lipid metabolism or severe hyperlipidemia with or without pancreatitis * Unstable diabetes mellitus or hyperglycemia * Stroke, embolism, collapse and shock, recent MI * Cholestasis due to any reason other than parenteral associated liver disease * Active new infection at time of initiation of Omegaven® * Hemodynamic instability * The patient may not be enrolled in any other clinical trial involving an investigational agent (unless approved by the designated physicians on the multidisciplinary team).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of Bilirubin | week 2, 3,4,and 8 | measurement of bilirubin level weekly. Available data reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omegaven All subjects will receive Omegaven
Omegaven: Omegaven® will be initiated at a dose of 0.5 gram/kg/day and is infused over 24 hours for 1-2 days, and then advanced to 1 gram/kg/day. Omegaven® will be infused intravenously through either a central or peripheral catheter alone or in conjunction with parenteral nutrition. Omegaven® will continue until weaned from PN. Monotherapy with Omegaven® can continue as an additional source of calories after the dextrose/protein portion of PN is discontinued. Omegaven may be restarted within seven days of discontinuing therapy. After seven days, and meeting inclusion criteria, Omegaven can resume at the initial dose of 0.5 grams/kg/day, advancing to 1 gm/kg/day. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Omegaven |
|---|---|
| Age, Categorical <=18 years | 15 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 89.3 days |
| bilirubin level | 6.79 mg/dL STANDARD_DEVIATION 4.14 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 1 / 15 |
Outcome results
Primary
Level of Bilirubin
measurement of bilirubin level weekly. Available data reported.
Time frame: week 2, 3,4,and 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omegaven | Level of Bilirubin | Week 2 N=12 | 7.4 mg/dL | Standard Deviation 4.38 |
| Omegaven | Level of Bilirubin | Week 3 N=8 | 6.63 mg/dL | Standard Deviation 4.39 |
| Omegaven | Level of Bilirubin | Week 4 N=10 | 7.97 mg/dL | Standard Deviation 6.5 |
| Omegaven | Level of Bilirubin | Week 8 N=11 | 4.72 mg/dL | Standard Deviation 4.81 |