Cholestasis, Cholestasis of Parenteral Nutrition
Conditions
Keywords
Omegaven, parenteral nutrition, Liver disease, Cholestasis
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
Interventions
DRUGOmegaven
Omegaven® fat emulsion will be used as a compassionate use treatment for critically ill infants with parenteral nutrition associated liver injury
Sponsors
University of South Florida
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
14 Days to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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® |
Countries
United States
Participant flow
Recruitment details
Infants were recruited from a single NICU for compassionate use of Omegaven for cholestasis.
Pre-assignment details
Infants were screened based on inclusion and exclusion criteria. When there was a potential candidate, an IND application is submitted to FDA.
Participants by arm
| Arm | Count |
|---|---|
| Drug - Omegaven® These infants were more than one month old with history of long-term TPN dependence due to intestinal problem. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Drug - Omegaven® |
|---|---|
| Age, Continuous | 45 days |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 2 |
| other Total, other adverse events | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Number of Participant With Decrease in Direct Bilirubin Level
Number of participant with decrease in direct bilirubin levels within 30 days of treatment
Time frame: First month of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug - Omegaven® | Number of Participant With Decrease in Direct Bilirubin Level | decrease in bilirubin level | 2 Participants |
| Drug - Omegaven® | Number of Participant With Decrease in Direct Bilirubin Level | increase or no change in bilirubin level | 0 Participants |
Secondary
Number of Participant With Preservation of Head Circumference
Monitoring of weekly head circumference while the patient is receiving Omegaven® treatment
Time frame: 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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug - Omegaven® | Number of Participant With Preservation of Head Circumference | preservation of head circumference | 2 Participants |
| Drug - Omegaven® | Number of Participant With Preservation of Head Circumference | Fail in head circumference growth | 0 Participants |
Secondary
Number of Participant With Preservation of Length
Monitoring of weekly length while the patient is receiving Omegaven® treatment
Time frame: 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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug - Omegaven® | Number of Participant With Preservation of Length | Preservation of length growth | 2 Participants |
| Drug - Omegaven® | Number of Participant With Preservation of Length | fail in length growth | 0 Participants |
Secondary
Number of Participant With Preservation of Normal Weight Gain
Monitoring of daily weight gain while the patient is on Omegaven®
Time frame: 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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug - Omegaven® | Number of Participant With Preservation of Normal Weight Gain | preservation of weight gain | 2 Participants |
| Drug - Omegaven® | Number of Participant With Preservation of Normal Weight Gain | fail in weight gain | 0 Participants |
Secondary
Number of Participant With Resolution of Direct Hyperbilirubinemia
Number of participant with Direct bilirubin level of \<2mg/dL at discontinuation of treatment
Time frame: 2 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Drug - Omegaven® | Number of Participant With Resolution of Direct Hyperbilirubinemia | bilirubin <2mg/dL at discontinuing of Omegaven | 1 Participants |
| Drug - Omegaven® | Number of Participant With Resolution of Direct Hyperbilirubinemia | bilirubin >2mg/dL at discontinuing of Omegaven | 1 Participants |