Compassionate Use of Omegaven to Reverse Parenteral Nutrition Induced Cholestasis

• Sponsor: Children's Hospital Medical Center, Cincinnati (Other)
• Overall Status: Completed
• CT.gov ID: NCT01173159
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 101
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research study is to see if giving Omegaven (an intravenous fat emulsion containing fish oil) instead of the current lipid emulsion, which contains fat derived from soybeans, as part of your child's intravenous (IV) nutrition therapy may be tolerated better. It may reduce the harmful effects to the liver, may stop any further liver damage and may reverse damage already done to the liver because of the prolonged use of nutrition through your child's IV.

Condition or Disease	Intervention/Treatment	Phase
Cholestasis	Drug: Omegaven	N/A

Detailed Description

Enrollment of subjects into this study will occur for up to 4 years. Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require total parenteral nutrition or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Compassionate Use of a Fish Oil-derived Intravenous Fat Emulsion (Omegaven) to Reverse Parenteral Nutrition (PN) Induced Cholestasis
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Omegaven Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require Total Parenteral Nutrition or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids.

Drug: Omegaven; For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Change in Conjugated/Direct Bilirubin [Completion of Therapy (time frame from 1-14 weeks)]

   Change in conjugated/direct bilirubin level to below 1 mg/dl.

Secondary Outcome Measures

1. Number of Participants With a Change in Unconjugated/Total Bilirubin [Completion of Therapy (time frame from 1-14 weeks)]

   Change in unconjugated/total bilirubin level to below 1.1 mg/dL. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.

2. Number of Participants With a Change in Aspartate Transaminase (AST) [Completion of Therapy (time frame from 1-14 weeks)]

   Change in aspartate transaminase (AST) 57 units/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.

3. Number of Participants With a Change in Liver Enzyme (ALT) [Completion of Therapy (time frame from 1-14 weeks)]

   Change in liver enzyme ALT to below 59 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.

4. Number of Participants With a Change in Liver Enzyme Alkaline Phosphatase [Completion of Therapy (time frame from 1-14 weeks)]

   Change in liver enzyme alkaline phosphatase to below 345 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.

5. Number of Participants With a Change in Liver Enzyme Gamma-glutamyltransferase (GGT) [Completion of Therapy (time frame from 1-14 weeks)]

   Change in Liver Enzyme Gamma-glutamyltransferase (GGT) to below 15 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.

6. Number of Participants With a Change in Triglycerides [Completion of Therapy (time frame from 1-14 weeks)]

   Change in Triglycerides to below 119 mg/dL. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females ages one month of age to 18 years of age

• Patients with intestinal failure on TPN

• Patients who have a conjugated/direct bilirubin of ≥3 mg/dl for more than weeks and in whom other causes of cholestasis have been excluded with reasonable certainty utilizing biochemical, serologic, microbiologic, and radiographic techniques. Liver biopsy is not required to rule out other disorders, but may be utilized at the clinician's discretion

• Patients in whom reduction of IV soy-based lipid to an average <1.2g/kg body weight/day has failed to reduce the conjugated/direct bilirubin within ≥ 30 days of implementation

• Willing to use birth control during study participation for females of child- bearing potential, as determined by investigator.

• Signed informed consent for use of Omegaven® obtained

Exclusion Criteria:

• Any of the contraindications to use of Omegaven®

• Impaired lipid metabolism (triglycerides >1000 mg/dL) while on

1g/kg/day or less of Intralipid

• History of severe hemorrhagic disorders (ie. hemophilia, Von Willebrand disease, etc.)

• Unstable diabetes mellitus

• Collapse and shock

• Stroke/ Embolism

• Cardiac infarction within the last 3 months

• Undefined coma status

• Pregnancy (positive pregnancy test) prior to enrollment in the study for females of child-bearing potential

• Females of child-bearing potential who are unwilling to use birth control during study participation

• Parental decision to forego the use of Omegaven®

• Known fish or egg allergy

• Pregnancy

• Causes of liver disease other than Parenteral Nutrition Associated Cholestasis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229

Sponsors and Collaborators

• Children's Hospital Medical Center, Cincinnati

Investigators

• Principal Investigator: Samuel Kocoshis, MD, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 2, 2015

More Information

Publications

None provided.

• Responsible Party: Children's Hospital Medical Center, Cincinnati
• ClinicalTrials.gov Identifier: NCT01173159
• Other Study ID Numbers: 2009-2314
• First Posted: Jul 30, 2010
• Last Update Posted: Jun 17, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Children's Hospital Medical Center, Cincinnati: Parenteral Nutrition; Cholestasis
• Additional relevant MeSH terms: Cholestasis

Study Results

Participant Flow

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require Total Parenteral Nutrition or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Overall Participants	10
Age (months) [Mean (Full Range) ]
Mean (Full Range) [months]	6
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%
Not Hispanic or Latino	9 90%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 40%
White	6 60%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Change in Conjugated/Direct Bilirubin
Description	Change in conjugated/direct bilirubin level to below 1 mg/dl.
Time Frame	Completion of Therapy (time frame from 1-14 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Measure Participants	10
Count of Participants [Participants]	4 40%

2. Secondary Outcome

Title	Number of Participants With a Change in Unconjugated/Total Bilirubin
Description	Change in unconjugated/total bilirubin level to below 1.1 mg/dL. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time Frame	Completion of Therapy (time frame from 1-14 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Measure Participants	10
Count of Participants [Participants]	5 50%

3. Secondary Outcome

Title	Number of Participants With a Change in Aspartate Transaminase (AST)
Description	Change in aspartate transaminase (AST) 57 units/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time Frame	Completion of Therapy (time frame from 1-14 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Measure Participants	10
Count of Participants [Participants]	2 20%

4. Secondary Outcome

Title	Number of Participants With a Change in Liver Enzyme (ALT)
Description	Change in liver enzyme ALT to below 59 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time Frame	Completion of Therapy (time frame from 1-14 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Measure Participants	10
Count of Participants [Participants]	1 10%

5. Secondary Outcome

Title	Number of Participants With a Change in Liver Enzyme Alkaline Phosphatase
Description	Change in liver enzyme alkaline phosphatase to below 345 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time Frame	Completion of Therapy (time frame from 1-14 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Measure Participants	10
Count of Participants [Participants]	3 30%

6. Secondary Outcome

Title	Number of Participants With a Change in Liver Enzyme Gamma-glutamyltransferase (GGT)
Description	Change in Liver Enzyme Gamma-glutamyltransferase (GGT) to below 15 unit/L. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time Frame	Completion of Therapy (time frame from 1-14 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Measure Participants	10
Count of Participants [Participants]	0 0%

7. Secondary Outcome

Title	Number of Participants With a Change in Triglycerides
Description	Change in Triglycerides to below 119 mg/dL. General outcomes of participants are reported due to the enrollment of very few patients so that we have too small a cohort with which to assess achievement of our stipulated outcomes.
Time Frame	Completion of Therapy (time frame from 1-14 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
Measure Participants	10
Count of Participants [Participants]	8 80%

Adverse Events

Time Frame	1 to 14 weeks of therapy
Arm/Group Title	Omegaven
Arm/Group Description	Subjects will receive Omegaven at a dose of up to 1 g/kg body weight/day until they no longer require TPN or until their conjugated/direct bilirubin has normalized and their enteral lipid intake is sufficient to discontinue intravenous lipids. Omegaven: For the first two days of treatment, subjects will receive Omegaven® at 0.5 g/kg per day to assess tolerance and will progress to a maintenance dosage of up to 1g/kg per day over 12 hours at an infusion rate of 1 g/kg/12 hours (10 ml/kg/12 hours). Dosing is based on previously described dosing of fish-oil emulsions as monotherapy noted within the literature. Omegaven® will be infused intravenously through either a central or peripheral catheter in conjunction with other parenteral nutrition containing dextrose and amino acids. Omegaven® is isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-site.
All Cause Mortality
	Omegaven
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	Omegaven
	Affected / at Risk (%)	# Events
Total	4/10 (40%)
Blood and lymphatic system disorders
Sepsis	1/10 (10%)	2
Thrombocytopenia	1/10 (10%)	1
Cardiac disorders
Sinus Bradycardia	1/10 (10%)	1
Hyperkalemia Causing Cardiac Dysrhythmia	1/10 (10%)	1
Cardiac Arrest	1/10 (10%)	1
Congenital, familial and genetic disorders
Multisystem Organ Dysfunction related to IPEX	1/10 (10%)	1
Gastrointestinal disorders
Gastrointestinal Hemorrhage	1/10 (10%)	1
Injury, poisoning and procedural complications
Compartment Syndrome Following Surgery	1/10 (10%)	1
Renal and urinary disorders
Acute Kidney Injury	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	Omegaven
	Affected / at Risk (%)	# Events
Total	6/10 (60%)
Blood and lymphatic system disorders
Thrombocytopenia	1/10 (10%)	1
Edema	2/10 (20%)	2
Triglycerides Increased	1/10 (10%)	1
Activated Partial Throboplastin Time Prolonged	1/10 (10%)	1
Platelet Count Decreased	1/10 (10%)	1
Abnormal CBC Differential with Active Bleeding	1/10 (10%)	1
Cardiac disorders
Ventricular Tachycardia	1/10 (10%)	2
Tachycardia and Tachypnea	1/10 (10%)	1
Gastrointestinal disorders
Gastrointestinal Fistula	2/10 (20%)	2
Blood in Stool	1/10 (10%)	1
Portal Hypertension	1/10 (10%)	1
General disorders
Vomiting	2/10 (20%)	3
Fever	3/10 (30%)	6
Upper Respiratory Infection	1/10 (10%)	1
Irritability	1/10 (10%)	1
Dried blood near Anus	1/10 (10%)	1
Lethargy	1/10 (10%)	2
Nasal Congestion	1/10 (10%)	1
Cough	1/10 (10%)	1
Hepatobiliary disorders
Gull bladder sludge with intrahepatice biliary ductal dilation	1/10 (10%)	1
Bleeding from nose	1/10 (10%)	1
Infections and infestations
Culture Positive from Tracheostomy	1/10 (10%)	1
Investigations
Phosporus Decreased	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Tachypnea	1/10 (10%)	1
Decreased Respiratory Rate	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Skin Irritation and breakdown	2/10 (20%)	2
Diaper Dermatitis	1/10 (10%)	1
Vascular disorders
Pulmonary Vein Stenosis	1/10 (10%)	1

Limitations/Caveats

We enrolled very few patients so that we have too small a cohort with which to assess achievement of our outcomes.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.