Compassionate Use of Omegaven to Reverse Parenteral Nutrition Induced Cholestasis - Full Text View

Purpose

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	Intervention
Cholestasis	Drug: Omegaven

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Drug Information available for: Parenteral Nutrition, Total

U.S. FDA Resources

Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:

Reduction in Conjugated/Direct Bilirubin [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
Primary endpoint - reduction in conjugated/direct bilirubin level to below 1 mg/dl. Previous studies suggest that conjugated/direct bilirubin will remain elevated for approximately 8 weeks. Subsequently, levels are expected to fall by approximately 1 mg/dl/week until they normalize. A patient who begins Omegaven® with a conjugated/direct bilirubin level of 7 mg/dl is likely to experience normalization within 14 weeks (8+6 weeks). We will compare the group receiving Omegaven® with historical controls from our internal registry who have demonstrated cholestasis while on Intralipid®.

Secondary Outcome Measures:

Normalization of total bilirubin and liver enzymes [ Time Frame: 14 weeks ] [ Designated as safety issue: No ]
Secondary endpoints will be: normalization of total bilirubin and liver enzymes. Differences in these values at the end of 14 weeks of therapy will be compared with those of controls via Kaplan-Meier analysis identical to that employed for conjugated/direct bilirubin levels. Furthermore, we expect that elevated triglyceride levels which might be present at the initiation of therapy will have normalized at the same time that liver profiles have normalized.

Estimated Enrollment:	25
Study Start Date:	July 2010
Estimated Study Completion Date:	July 2015
Estimated Primary Completion Date:	July 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Omegaven 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.	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.

Arms

Assigned Interventions

Experimental: Omegaven

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.

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.

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.

Eligibility

Ages Eligible for Study:	1 Month to 18 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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 PNAC

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01173159

Contacts

Contact: Crystal Slaughter, BA

513-636-0137

crystal.slaughter@cchmc.org

Locations

United States, Ohio
Cincinnati Children's Hospital Medical Center	Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Crystal Slaughter, BA 513-636-0137 crystal.slaughter@cchmc.org
Contact: Misty Troutt 513-803-1531 misty.troutt@cchmc.org
Principal Investigator: Samuel A Kocoshis, MD

Sponsors and Collaborators

Children's Hospital Medical Center, Cincinnati

Investigators

Principal Investigator:

Samuel Kocoshis, MD

Children's Hospital Medical Center, Cincinnati

More Information

No publications provided

Responsible Party:	Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:	NCT01173159 History of Changes
Other Study ID Numbers:	2009-2314
Study First Received:	July 29, 2010
Last Updated:	April 12, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Children's Hospital Medical Center, Cincinnati:

Parenteral Nutrition
Cholestasis

Additional relevant MeSH terms:

Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on May 16, 2013