Conditions: Total Parenteral Nutrition-induced Cholestasis
Keywords: PNALD Cholestasis Omegaven® Short Bowel Syndrome
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 11
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine whether the omega-3 fatty acid emulsion (Omegaven®), when used in place of the conventional soy-based fat emulsion (Intralipid), is effective in treating parenteral nutrition associated liver disease (PNALD) in children.

The study hypothesis is that Omegaven® can be safely provided to children who are dependent on parenteral nutrition and have PNALD, and can reverse or prevent progression of PNALD until the child can take adequate nutrition by mouth.

Detailed description:
Rationale for Omegaven® Treatment

Unlike conventional intravenous fat emulsions, Omegaven® is comprised solely of fish oils containing primarily omega-3 fatty acids. Animal studies have shown that IV lipid emulsions such as fish oil that are high in eicosapentaenic and docosahexaenoic acid reduce impairment of bile flow as seen in cholestasis caused by conventional fat emulsions(1,2). By administering Omegaven® in place of conventional phytosterol/soybean fat emulsions, the cholestasis may be reversed and patients will be able to be maintained on adequate PN until they are able to ingest adequate nutrition enterally.

References

1. Chen W. Effects of fat emulsions with different fatty acid composition on plasma and hepatic lipids in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:24.
2. Yeh S. Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:80.

Arms:
arm 1: Single Omegaven® Intervention Arm

Interventions: intervention 1: Omegaven®
Intervention descriptions: intervention 1: 10% Omegaven® initiated at a starting dose of 0.5g/kg/day for two days and then advancing to the goal dose of 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated.

Protocol document:
ICF_001.pdf: 
Official Title:  Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in the 
Treatment of Parenteral Nutrition (PN) Induced Liver Injury
IRB-Approved Date: 7/21/2010
NCT01845116


Omegaven 
July 21, 2010 
Expiration: July 20, 2011 
Page 1 of 8  
Patient/Parent Initials_______ 
MRN/History#____________________ 
CAROLINAS HEALTHCARE SYSTEM 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in the Treatment 
of Parenteral Nutrition (PN) Induced Liver Injury 
INTRODUCTION 
Dr. Caicedo and his associates are asking you/your child to participate in the Omegaven 
study at Levine Children’s Hospital (LCH) and Carolinas HealthCare System (CHS).  
You are asked to enroll or enroll your child in this study due to liver damage from being 
fed by an IV (intravenously, meaning by a vein), and the study team believes that you or 
your child may benefit from this medication.  We anticipate that you/your child will be 
enrolled in the study for at least six months, and that you/your child will be one of 
approximately five patients enrolled each year at CHS. 
HOW THE STUDY WORKS 
You are being asked to enroll or enroll your child in a study. You/your child has 
intestinal failure, meaning you/your child’s intestine cannot absorb enough nutrients to 
grow.  Therefore, you/your child has required special nutrition (“TPN” or PN) that is 
given by an IV.  This IV nutrition is necessary and life saving, but it can result in severe 
liver disease.  You/your child was chosen for this study because you/your child has 
developed chronic liver disease that is getting worse.  Research studies have shown that 
the IV fat mixture (called Intralipid®), which is part of your/your child’s IV nutrition, 
may be contributing to the liver disease. An alternative form of the IV fat mixture, called 
Omegaven®, could be used in place of Intralipid® for you/your child. Omegaven® has 
10% fish oil, which is different from Intralipid®, which contains soybean oils.  In studies 
performed in Europe, Canada and the U.S., infants and children treated with Omegaven® 
showed reversal in the signs of liver damage from being fed through a vein. 
Currently, Omegaven® is not approved for use in the U.S. and is considered 
investigational. This means that the drug has not been approved by the Food and Drug 
Administration (FDA).  However, due to your/your child’s condition, we have received 
permission through the FDA to make Omegaven® available to you/your child.   
Omegaven® is given IV through a small tube placed in a small vein or larger vein deep 
within the body.  Omegaven® is given along with other solutions that have dextrose 
(sugar) and amino acids (protein).  No other fat mixtures will be given during the time 
Omegaven® is being given, since we believe the other mixtures are contributing to 
your/your child’s liver disease. 


Omegaven 
July 21, 2010 
Expiration: July 20, 2011 
Page 2 of 8  
Patient/Parent Initials_______ 
MRN/History#____________________ 
Omegaven® can be given either in the hospital or as a home infusion, but the first dose 
will be given in the hospital.  If Omegaven® is given on an outpatient basis, you/your 
child will be required to return to Levine Children’s Specialty Center once a month or 
other mutually agreed upon schedule for evaluation and follow-up.  Per the study, your 
home health care agency will make arrangements for the required weekly or monthly 
blood draws you/your child will need while at home in order to remain on Omegaven®.  
The lab results will then be faxed to the Pediatric Nutrition Support Clinic at the Levine 
Children’s Specialty Center at 
. 
RISKS AND DISCOMFORTS 
Previous studies have shown no special risks of using this drug in humans. As with all 
medications, side effects may include allergic reaction. Allergic reaction may range from 
minor itching or rash to major reactions which can result in death. The manufacturer has 
indicated that there may be increased risk of an allergic reaction to this product in 
patients with egg or shellfish allergies.  Omegaven® is not recommended for patients 
with impaired lipid metabolism (break down of fat in the body), severe hemorrhagic 
(bleeding) disorders, or unstable diabetes mellitus when blood sugars are not well 
controlled. 
Due to lack of experience in certain life threatening situations, the manufacturer does not 
recommend the use of Omegaven® in patients with severe liver or renal insufficiency 
(liver or kidney problems/disorders).  Therefore, the risk associated with using 
Omegaven® in you/your child, given that you/your child has severe liver injury, is not 
known. 
Risks seen while Omegaven® is given include: 
Likely: 
•
There may be an association with essential fatty acid deficiency, or elevated free
fatty acids or triglycerides (other types of fat in the blood)
Less Likely: 
•
Fishy taste
Rare but Serious: 
•
Prolonged bleeding time
•
Infections
•
Sharp increases in blood sugar levels


Omegaven 
July 21, 2010 
Expiration: July 20, 2011 
Page 3 of 8   
Patient/Parent Initials_______ 
MRN/History#____________________ 
 
 
 
Undesirable effects that are seen while Omegaven® is given, that may also occur with 
conventional fat (for example: Intralipid®) include: 
Likely: 
• Slight rise in body temperature 
• Heat sensation and/or cold sensation 
• Feeling of heat sensation of face/neck 
• Allergic reactions/redness to skin 
 
Less Likely: 
• Chills 
• Lack of appetitie, nause, vomiting 
• Headache, pain in the chest, bone pain 
 
Rare but Serious: 
• Difficulty breathing 
• Increase/decrease in blood pressure 
• Painful erection of the penis that can last for more than one hour 
 
 The long term side effects of Omegaven® are not known, and there is a risk that the drug 
may cause bleeding to occur on its own, meaning there are no other reasons for bleeding 
to happen.  Because of this, blood tests will be performed regularly (about every 2 weeks) 
to monitor how you/your child is handling the treatment (how the blood clots and the 
level of fatty acids in the blood).  The amount of blood that is collected will not be more 
than 3 milliliters (less than 1 teaspoon),  in addition to the standard lab work that is used 
to help follow you/your child. Risks associated with blood drawing may include pain, 
bruising, and infection.  Rarely, a person faints.  If we determine that there are significant 
changes in any lab tests or the way in which you/your child can handle the lipids, we may 
choose to stop the study.  We will discuss these decisions with you. 
 
Other side effects may exist which are not known yet. If any new information is learned 
during the study, it will be shared with all participants. 
 
Reproductive Risks 
The effects of Omegaven® on the reproductive system (sperm, eggs) or to a developing 
unborn baby are not known. Because of this, patients who are on Omegaven® should not  
 
 


Omegaven 
July 21, 2010 
Expiration: July 20, 2011 
Page 4 of 8  
Patient/Parent Initials_______ 
MRN/History#____________________ 
become pregnant.  For entry into this study, we require that all participants who are of 
appropriate age, agree to abstain from sexual intercourse (cannot have sex while on  
Omegaven®) or use a reliable, effective contraception (such as condoms or birth control 
pills) while on Omegaven®. 
If of appropriate age and sex, before your child starts on the study, a confidential 
pregnancy test will be performed. Results will be given to the child by one of the study 
doctors or investigators.  Every effort will be made to maintain confidentiality regarding 
a positive pregnancy test. Our policy is that we would not tell parent(s) or guardian(s) 
without the child’s permission. However, under certain circumstances, we may have to 
share this information. For example, if your child’s life or someone elses’s life was at risk 
or if abuse was suspected, then it may be necessary to tell you as parent(s) or guardian(s) 
of a positive pregnancy test. 
If we feel that it is necessary to tell a parent or guardian of a positive pregnancy test, we 
would meet privately with your child first to discuss our concerns before sharing any 
information regarding the pregnancy.  If your child becomes pregnant while receiving 
Omegaven®, we will need to withdraw your child from the study.  This means that even 
if we do not share results, parent(s) or guardian(s) may suspect pregnancy despite our 
best efforts to maintain confidentiality.  If your child becomes pregnant or if there is any 
chance that your child is pregnant (late menstrual period), please contact the study team 
immediately so we may provide medical assistance and counseling. 
BENEFITS 
This study may or may not improve your/your child’s condition. The information gained 
from your/your child’s case may benefit others with your/your child’s condition. 
EXCLUSION CRITERIA 
•
Pregnancy
•
Other causes of chronic liver disease (cystic fibrosis, biliary atresia, alpha-1
antitrypsin deficiency)
•
Signs of advanced liver disease including cirrhosis on biopsy (where the liver has lost
its ability to function normally due to chronic injury), varices (swollen veins in the
lining of the stomach due to liver disease), ascites (abnormal collection of fluid in the
abdomen due to liver disease)
•
Known allergy to fish or egg protein
•
Inability to properly break down fat in the body
•
Severe bleeding disorders


Omegaven 
July 21, 2010 
Expiration: July 20, 2011 
Page 5 of 8  
Patient/Parent Initials_______ 
MRN/History#____________________ 
•
Unstable diabetes mellitus where blood sugars are not well controlled
•
Low blood pressure that causes the body’s organs not to get good blood flow and
oxygen
•
Stroke
•
Recent heart attack
•
Undefined coma (unconsciousness) status
•
Enrolled in any other clinical trial involving an investigational agent
(unless approved first by Dr. Caicedo, the clinical study investigator)
ALTERNATIVE PROCEDURE/TREATMENT 
Participation to use Omegaven® is entirely voluntary. If you choose not to use 
Omegaven®, the alternative treatment is to continue the current treatment you/your child 
is receiving.  This includes the use of soy based fats in the nutrition by vein.  The use of 
the soy based fats have been standard practice for the past 25 years. 
ADDITIONAL COST 
The FDA has approved charging for the cost of Omegaven®. The cost of Omegaven® is 
the same as the cost of the fats given now by vein.  Your insurance company may not pay 
for research treatments.  If the insurance plan does not pay, then CHS Healthy @ Home, 
LLC, will cover all of the costs of the infusion of Omegaven®.   
COMPENSATION 
You will not be compensated in any way for participation in this study. 
In the event that you/your child are harmed as a result of your participation in this study 
protocol, we will provide or arrange for treatment as necessary.  This treatment, as well 
as other medical expenses, will be billed to you or your insurance company in the usual 
manner. 
WITHDRAWAL 
Your participation in this study is completely voluntary. You should feel under no 
pressure to be in this Omegaven® study.  If you decide not to be in this study, you will 
not in any way harm your relations with your doctors or with LCH or CHS.  You are free 
to stop your child or yourself from being in the study if you change your mind after 
entering it.  This would not harm your relations with your doctors or with LCH or CHS.  
We will tell you about new medical findings that may affect your willingness to continue 
in the study. 


Omegaven 
July 21, 2010 
Expiration: July 20, 2011 
Page 6 of 8  
Patient/Parent Initials_______ 
MRN/History#____________________ 
CONFIDENTIALITY: 
The records of this study will be kept private.  In any sort of report we might publish, we 
will not include any information that will make it possible to identify a patient.  
Your/your child’s record for this study protocol may, however, be reviewed and/or 
photocopied by Carolinas HealthCare System, or by representatives of the Food and Drug 
Administration or other government agencies.  To that extent, confidentiality is not 
absolute.   
AUTHORIZATION: 
If you wish to have your child/yourself take part in this clinical study protocol, you will 
be asked to sign this consent form.  It allows the study investigator to collect, process and 
pass on any relevant personal health information collected from your/your child during 
the study.  These are the activities routinely carried out during all clinical studies: 
You have been told that personal information about you/your child (including sensitive 
personal health information, such as your/your child’s medical history and your/your 
child’s racial/ethnic origin if relevant to the study) will be reviewed, collected on a 
computer database, stored in electronic or manual files, audited, and/or otherwise 
processed by: 
•
The clinical study investigator, Dr. Caicedo and research staff,
•
regulatory or other governmental authorities of the United States and other
countries,
•
Carolinas HealthCare System employees,
•
other persons or agencies as required by law or allowed by federal regulations.
You have been told that your/your child’s personal data will be collected and processed 
to: 
•
Check your/your child’s suitability to take part in the study,
•
monitor your/your child’s treatment with the study medication,
•
compare and pool treatment results with those of other subjects in clinical studies,
•
support the development of the study medication,
•
support the licensing application for regulatory approval of Omegaven® in the
world,
•
support the marketing, distribution, sale and use of Omegaven® anwhere in the
world.
FINANCIAL INTEREST OF INVESTIGATOR 


Omegaven 
July 21, 2010 
Expiration: July 20, 2011 
Page 7 of 8  
Patient/Parent Initials_______ 
MRN/History#____________________ 
The doctors will receive no financial benefit in any form by asking you to participate in 
this study. 
QUESTIONS 
The physicians offering this study at Levine Children’s Hospital and Carolinas 
HealthCare System are Dr. Ricardo Caicedo at 
;  Dr. Michelle Chiu and Dr. 
Karen Lessaris at 
.  You may ask them any questions you have now.  If you 
have questions later, you may contact: 
Dr. Caicedo at: 
Drs. Chiu and Lessaris at: 
Department of Pediatric Gastroenterology 
Department of Neonatology 
 
 
 
 
 
  
 
 
 
The Institutional Review Board is a group of people who review the research to protect 
your/your child’s rights.  If you have questions about the conduct of this study or about 
your/your child’s rights as a reasearch subject, you may call the chairperson of the 
Institutional Review Board of Carolinas HealthCare System for information regarding 
patients’ rights in a reserarch study.  You can obtain the name and number of this person 
by calling 
. 
(This space intentionally left blank.)


Omegaven 
July 21, 2010 
Expiration: July 20, 2011 
Page 8 of 8  
Patient/Parent Initials_______ 
MRN/History#____________________ 
CONSENT 
I have read the above information.  I have asked any questions I had, and those questions 
have been answered.  I agree for myself/my child to be in this study and authorize the use 
of my/my child’s personal health information.  If of childbearing age, I will us or I agree 
for my child to use birth control during the time that I am/she is receiving Omegaven®.   
Dr. Caicedo or one of his associates will give me a copy of this form. 
_______________________________ 
_______________ 
__________________ 
Patient (guardian) Print Name 
Date 
 
Time 
_______________________________ 
________________ __________________ 
Patient (guardian) Print Name 
Date 
 
Time 
_______________________________ 
________________ __________________ 
Signature of Person Obtaining Consent 
Date 
 
Time 
_______________________________ 
________________ __________________ 
Investigator Signature  
Date 
 
Time 
Identity of representative 
___Next of Kin 
___Parent/Guardian 
___Healthcare Power of Attorney 

Prot_000.pdf: 
Official Title: Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in 
the Treatment of Parenteral Nutrition (PN) Induced Liver Injury 
NCT01845116 
Date:  7/21/2010 
 


 
- 2 - 
 
                           
Patient Information 
CAROLINAS HEALTHCARE SYSTEM 
EXPERIMENTAL DESIGN/STUDY PROTOCOL 
July 21, 2010 
 
Protocol Title:  
Use of a Fish Oil-Based Intravenous Lipid Emulsion (Omegaven®) in the Treatment 
of Parenteral Nutrition (PN) induced Liver Injury 
 
BRIEF SUMMARY OR ABSTRACT OF THIS PHASE II CLINICAL TRIAL 
STUDY PROTOCOL 
In the United States, patients dependent upon parenteral nutrition (PN) receive parenteral 
lipid emulsions composed of soybean oils. Lipids are necessary in PN dependent patients 
due to their high caloric value and essential fatty acid content. They have been implicated 
in predisposing patients to PN associated liver disease (PNALD). Phytosterols such as 
those contained in soybean oils are thought to have a deleterious effect on biliary 
secretion.  Accumulation of lipids in the hepatic Kupffer cells may further impair liver 
function. 
 
Children requiring prolonged courses of PN are at risk for developing PNALD.  It is s 
hypothesized that although omega-6 fatty acid emulsions prevent fatty acid deficiency, 
they are not cleared in a manner similar to enteral chylomicrons and therefore accumulate 
in the liver and result in steatotic liver injury. It is further hypothesized that a fat 
emulsion comprised of omega-3 fatty acids (i.e., fish oil) such as Omegaven® would be 
beneficial in the managemet of steatotic liver injury by its inhibition of de novo 
lipogenesis, the reduction of arachidonic acid-derived inflammatory mediators, 
prevention of essential fatty acid deficiency through the presence of small amounts of 
arachidonic acid, and improved clearance of lipids from the serum. Animal studies have 
shown that IV fat emulsions (IFE) such as fish oil that are high in eicosapentaenic and 
docashexaaenoic acid reduce impairment of bile flow which is seen in cholestasis caused 
by conventional fat emulsions.  Furthermore, it is  hypothesized that intravenous omega 
three fatty acids will be well tolerated and might reduce the inflammatory effect in the 
liver of prolonged PN exposure and could potentially reverse any hepatic dysfunction due 
to 
PN/IFE 
use. 
By 
administering 
Omegaven® 
in 
place 
of 
conventional 
phytosterol/soybean lipid emulsions, we may reverse or prevent the progression of PN 
associated cholestasis and thus allow the patient to be maintained on adequate PN until 
they are able to ingest adequate nutrition enterally. 
 
PHASE II CLINICAL TRIAL HYPOTHESIS 
The administration of Omegaven® in place of conventional phytosterol/soybean lipid 
emulsions will be safely provided to children with intestinal failure (defined as inability 
to wean from PN, with causes including short bowel syndrome) and PNALD and will 
reverse or prevent the progression of PN associated cholestasis and will allow the patient 
to be maintained on adequate PN until they are able to ingest adequate nutrition enterally. 
 
 
 


 
- 3 - 
 
                           
Patient Information 
SPECIFIC AIMS/OBJECTIVES 
• 
To determine the impact of Omegaven® on reversal of conjugated hyperbilirubinemia 
• 
To determine the impact of Omegaven® on the prevention of essential fatty acid 
deficiency 
• 
To determine the impact of Omegaven® administration on serum triglyceride 
• 
To determine the impact of Omegaven® administration on coagulation profiles 
 
BACKGROUND AND SIGNIFICANCE 
Parenteral Nutrition Associated Liver Disease (PNALD) 
 
Parenteral nutrition (PN) provides intravenous nutritional supplementation for patients 
unable to absorb adequate enteral nutrients secondary to insufficient intestinal length or 
function. PN contains the macronutrient building blocks of the human diet in their most 
elemental forms (amino acids and dextrose) and is commonly administered with a lipid 
emulsion to avoid essential fatty acid deficiency and to provide a calorically dense source 
of non-protein calories. In addition, PN contains the essential micronutrients 
(electrolytes, trace elements, and vitamins) to provide an optimal nutritional regimen. 
Before the development of PN in the late 1960’s, patients with insufficient 
gastrointestinal absorptive function commonly died of starvation and subsequent 
complications of malnutrition (1, 2). Today, more than 30,000 patients are permanently 
dependent on PN for survival. However, PN continues to be associated with hepatic 
injury that occurs at an unpredictable rate and includes both biochemical, i.e., elevated 
serum aminotransferase and alkaline phosphatase, and histologic alterations such as 
steatosis, steatohepatitis, lipidosis, cholestasis, fibrosis, and cirrhosis (3, 4). These 
abnormalities, which may worsen with the duration of PN administration, are more 
prevalent in the pediatric population. Additional risk factors for this condition include 
prematurity, low birth weight, long-term use of PN, the lack of concomitant enteral 
intake, systemic infections, and multiple operative procedures(5). 
  
Although the pathological features of PN-induced liver injury have been well described, 
the etiology, prevention, and treatment of this complication are not well understood. 
Multiple hypotheses exist to explain the pathogenesis of PN-induced liver injury 
including altered gut hormonal profiles (6), the propensity for bacterial translocation in 
the absence of enteral intake (7, 8), intestinal stasis resulting in the reduced clearance of 
hepatotoxic bile acids (8), and direct deficiencies or toxic components of the PN solution 
itself resulting in excessive glucose calorie uptake, excessive lipid infusion, or nutritional 
deficiencies such as essential fatty acid deficiency (9-11). None of these theories has been 
confirmed consistently. The etiology of PN-associated liver disease is currently 
considered multifactorial. Available treatment options for this disease process are limited 
and have achieved moderate success at best. Care of the PN-dependent patient is focused 
on gradually increasing enteral caloric intake as the residual bowel adapts allowing  PN 
to be discontinued  (12).  In fact, it has been shown both experimentally and clinically 
that partial enteral nutrition, when tolerated, helps to protect against the development of 
PN-associated liver injury (13-15). In severe cases of refractory hepatic failure, liver 
transplantation with or without accompanying small bowel transplantation remains the 
only treatment option.  
 


 
- 4 - 
 
                           
Patient Information 
Role of Intravenous Fat Emulsion on PN Associated Liver Disease 
 
Recent evidence demonstrates that lipids are metabolized differently depending on their 
route of administration. Enteral lipids are absorbed by the enterocyte in the small bowel 
mucosa in the form of a micelle and packaged into chylomicrons which are released into 
the portal venous system for ultimate uptake and disposal in the liver. Once in the 
bloodstream, these particles rapidly acquire apolipoproteins from circulating high-density 
lipoproteins and can subsequently be metabolized by the liver. The emulsified particles of 
commercially made and intravenously administered lipid emulsions, such as Intralipid®, 
mimic the size and structure of chylomicrons, but differ in their content. In contrast to 
chylomicrons, artificial lipid particles primarily contain essential fatty acids and omega-6 
triglycerides and are devoid of cholesterol or protein. Recent studies suggest that these 
omega-6 fatty acid-containing emulsions are dependent on lipoprotein lipase, 
apolipoprotein E, and low-density lipoprotein receptors for clearance, and are 
metabolized with less lipolysis and release of essential fatty acids than are chylomicrons. 
In fact, it appears that they may be cleared as whole particles by tissues other than the 
liver.(16) These factors may account for the increased incidence of steatohepatitis 
associated with the intravenous administration of Intralipid®. 
 
The mechanism of clearance of omega-3 fatty acid containing lipid emulsions is 
unknown, but appears to be largely independent of the pathways identified above (17). 
Furthermore, omega-3 fatty acid solutions have been shown to decrease de novo 
lipogenesis (18), prevent or attenuate PN-induced hepatosteatosis in rats (19) and guinea 
pigs, and ameliorate the severity of high-fat diet-induced hepatosteatosis in rats (20). In 
addition, omega-3 fatty acids can interfere with the arachidonic acid pathway of 
inflammation (18, 21). They can displace arachidonic acid from tissue fatty acid pools, 
thereby reducing the availability for eicasanoid-synthesizing enzymes and inflammation 
(21).  
  
Table 1 summarizes the composition of Intralipid® and Omegaven fat emulsions. 
                                                                                                                                                  
Rationale for Omegaven® Treatment 
 
Unlike conventional intravenous fat emulsions, Omegaven®  is comprised solely of fish 
oils containing primarily omega-3 fatty acids. Animal studies have shown that IV lipid 
emulsions such as fish oil that are high in eicosapentaenic and docosahexaenoic acid 
reduce impairment of bile flow as seen in cholestasis caused by conventional fat 
emulsions(19,20). By administering Omegaven® in place of conventional 
phytosterol/soybean fat emulsions, the cholestasis may be reversed and  patients will be 
able to be maintained on adequate PN until they are able to ingest adequate nutrition 
enterally. 
 
PRELIMANARY STUDIES/PROGRESS REPORT 
Animal Studies 
 


 
- 5 - 
 
                           
Patient Information 
The development of PN-associated liver injury may be dependent on both the route and 
quantity of lipid administration.  Also, omega-3 fatty acids are thought to prevent or 
reduce de novo lipogenesis and the subsequent liver injury independent of the route of 
administration. Specifically, a previously established murine model of PN-associated 
liver injury was used to investigate whether enteral lipid administration would protect 
against the development of steatohepatitis in PN-dependent animals. In this murine 
model, steatohepatitis is largely due to a high carbohydrate load and essential fatty acid 
deficiency. Although this model is not replicative of the clinical setting, it is a model that 
maximizes liver steatosis. In this model, mice are treated with oral PN for 19 days before 
being sacrificed. These animals develop severe fatty liver changes demonstrated by MRI 
spectroscopy and histology (H&E, PAS, and oil red O staining), and also have 
biochemical changes consistent with liver injury (elevated alkaline phosphatase and 
serum transaminases). Experimental groups were supplemented with Intralipid® by 
several routes of administration including orally, intravenously, and subcutaneously. 
Other groups were also supplemented with omega-3 fatty acids (Omegaven®) by the 
same routes of administration.  This study found a consistent pattern of protection against 
PN-associated steatohepatitis by administering enteral Intralipid® (22). In mice that 
received the highest dose of enteral Intralipid®, there was a marked decrease in the extent 
of overall liver injury as measured by gross inspection, histologic analysis, liver fat 
content, and serum liver enzyme levels. In all areas of this investigation, mice treated 
with enteral lipid most closely resembled the control mice that did not receive PN as part 
of the experimental protocol. These results were in complete contrast to the extensive 
fatty infiltration and evidence of hepatic injury found in mice that received PN without 
lipid supplementation, as well as in mice that received PN with intravenous Intralipid®. 
Mice receiving intravenous Intralipid® had the most severe liver changes.  Both groups 
of animals developed marked hepatic steatosis with macrovesicular fatty infiltration and 
significant elevations in spectroscopic liver fat content and serum transaminase levels. In 
addition, the effect of enteral Intralipid® supplementation appeared to be dose-
dependent; mice receiving one-third the dose of enteral Intralipid® showed improved 
liver histology but still demonstrated a moderate degree of liver injury by spectroscopy 
and serum liver function tests.  
 
The nutritional model employed in this study provided all experimental mice with enteral 
PN solution ad libitum. In this way, mice were not force-fed PN and self-regulated their 
PN intake by demands for growth and energy. Importantly, all mice gained weight 
throughout the 19-day protocol, and there were no differences in weight gain parameters 
between the groups. The PN solution was a typical pediatric stock containing 20% 
dextrose and 2% amino acids. Each milliliter of this formula provides 0.2 g (0.68 
kilocalories) of dextrose and 0.02 g (0.08 kilocalories) amino acid. As the daily intake per 
animal of PN averaged 15 ml, mice were ingesting approximately 11.4 kilocalories/day 
and 456 kilocalories/kg/day. This caloric load is similar to the established dietary energy 
needs of the mouse (23). The parenteral fat source used in this study was Intralipid® 20% 
(Baxter, Deerfield, Illinois), which is a soybean oil-based emulsion. Each milliliter of this 
emulsion contains 0.2 g (2.0 kcal) of fat.  It is recognized that the model may not 
completely match the clinical, human setting of intravenous PN-administration; however, 
the goal was to produce a fatty liver with biochemical evidence of injury.  


 
- 6 - 
 
                           
Patient Information 
  
In a second set of experiments, the same murine model was used to determine whether 
Omegaven®, a commercial fish oil emulsion available in Europe, would prevent fatty 
liver changes by enteral or parenteral routes of administration, and to determine the 
serum fatty acid profile of these animals. Animals receiving Omegaven® via the oral and 
intravenous routes had completely normal livers on histology and MRI spectroscopy 
revealed normal liver fat content. Liver functions tests in orally treated animals were also 
within the norm, while there were minimal elevations in intravenously treated groups. 
There was no fatty acid deficiency in these groups as determined by Mead acid (5, 8, 11-
Eicosatrienoic acid) levels in the serum fatty acid analysis. Mead acid is the only 
polyunsaturated fatty acid of note produced de novo by animals and only accumulates 
under the conditions of essential fatty acid deficiency.  Furthermore, arachadonic acid 
levels were low in Omegaven® treated animals consistent with previous reports. In a 
third set of experiments, mice were made severely fatty acid deficient. These mice were 
treated for 10 days with Omegaven® and had complete reversal of their fatty acid 
deficiency. 
 
Similarly, other investigators studied livers in a newborn pig model and  showed that 
intravenous administration of fish oil, which consists primarily of omega-3 fatty acids, 
reduced parenteral nutrition-induced cholestasis.(22) However, the study was only 3 
weeks in duration and long-term effects from administration of omega-3 fatty acids alone 
were not evaluated.  In fact, the idea that one could remove an essential fatty acid from 
the standard regime of nutritional support by PN has not been accepted.  It has been 
thought that reduction of an essential fatty acid, such as omega-6, during long-term 
therapy would result in fatty acid deficiency and deterioration of the health of the patient. 
The Children’s Hospital Boston’s experience to date, demonstrates that the use of 
Omegaven® as monotherapy does not result in the development of essential fatty acid 
deficiency and it can actually be used to as monotherapy to treat this deficiency state.   
 
Preliminary Safety and Efficacy Data for Use of Omegaven® in Other Diseases 
 
Omegaven® has been used for over 10 years as an adjunct to conventional fat emulsions.  
According to current data, an increase in the proportion of omega-3 fatty acids is thought 
to optimize nutrition in general, but in particular benefit patients whose underlying 
disease might benefit from an increase in omega-3 fatty acids.  An adequate intake of 
omega-3 fatty acids results in anti-inflammatory and immunomodulatory effects that are 
protective in nature from inflammatory tissue damage, capillary permeability, and 
improved immunological resistance. It may also reduce the risk of thrombosis and 
increase microvascular perfusion due to its anti-aggregatory and vasodilatory effects. 
 
In Europe and Asia, the use of parenteral omega-3 fatty acids has been used in the 
following adult patient populations (24-28): 
 
- Post traumatic and post surgical patients 
 
- Patients experiencing early stages of sepsis/SIRS 
 
- Patients at risk of hyperinflammatory processes 
 
- Patients with inflammatory bowel disease (Crohn’s disease, ulcerative colitis) 


 
- 7 - 
 
                           
Patient Information 
 
- Patients with inflammatory skin diseases (psoriasis, atopic eczema) 
 
The dosing used in these patients was 0.1 g (1 ml) to a maximum of 0.2 (2 ml) /kg body 
weight. The infusion rate used did not exceed 0.5 ml/kg/body weight/hour.  Since it was 
intended to be infused in combination with conventional fat emulsions, the total fat intake 
was limited to 10-20% as fish oil.  The duration of administration did not exceed 4 
weeks. 
 
Preliminary Safety and Efficacy Data for Use of Omegaven® in Infants 
 
     Initial pediatric experience with Omegaven® was limited to 2 unpublished clinical 
trials (see reference).  These trials were performed in Germany and Taiwan (29). The 
German study was a controlled, randomized, open parallel-group clinical study to 
investigate whether or not omega-3 fatty acids could be incorporated into the plasma 
phospholipids of very low birth weight preterm infants.  In this 7-day safety trial, 
Omegaven® use was evaluated on the basis of clinical, laboratory, and antioxidant 
parameters and lipid metabolism. Treatment was started on day 3-5 of life and continued 
for a total of 7 days. Patients received Omegaven® plus conventional soybean fat 
emulsion or soybean emulsion alone.  The maximum dose of Omegaven® in the study 
was 0.2 gm/kg/day.  The study concluded that the Omegaven® was well tolerated in this 
group of preterm infants in respect to both hematological and biochemical parameters. 
The incidence of reported adverse events between both study groups was similar. The 
eicosapentaenoic acid (EPA) content of plasma phospholipids increased significantly in 
the Omegaven® arm, with the proportion of EPA to the total fatty acids reaching almost 
three times the baseline value. The sum of omega-3 fatty acids showed a significantly 
greater increase in the Omegaven® group compared to the conventional treatment arm. 
 
     The Taiwanese study was a single center, controlled, open-labeled study conducted to 
investigate the safety of parenteral administration of Omegaven in preterm infants. The 
group of 20 infants were randomized to one of two treatment groups; one consisting of 
Omegaven®/conventional lipids and the other consisting of conventional lipids alone.  
The average dose of Omegaven® in the treatment group of this 14-day study was 0.13 + 
0.02 g/kg/day.  There were no significant differences between the two groups with regard 
to body weight and length. Similarly, there was no significant difference in the 
hematological or biochemical parameters.  There were no adverse events that were 
attributable to Omegaven® use. It was concluded that Omegaven® was well tolerated in 
these preterm infants. 
 
Experience in PN Liver Injury 
 
A single patient with bridging fibrosis due to prolonged parenteral nutrition use has been 
treated by compassionate use with Omegaven® at Children's Hospital, Boston (IRB 
approval # E04-09-006, FDA IND # 69,208). By age 6 months, this male infant was 
listed for a liver-small bowel transplant due to severe hepatic disease. His liver biopsy 
showed predominantly centrilobular, hepatocellular damage with ballooning of the 
hepatocytes, cholestasis, local steatosis, focal giant cell transformation, expansion of 


 
- 8 - 
 
                           
Patient Information 
portal tracks with mild inflammation, bile duct proliferation, mild fibrosis, and mild 
periportal iron deposits. On a subsequent biopsy, he progressed to bridging fibrosis.  
Omegaven® was started at a dose of 0.2 g/kg/day IV and advanced by 0.2 g/kg/day 
increments to 1 g/kg/day over a 14-day period. In order to ensure adequate caloric intake, 
additional non-protein calories were provided as parenteral carbohydrates (as dextrose).  
No other parenteral form of fat emulsion was administered during Omegaven® therapy.  
His enteral feeds were advanced while on the Omegaven®. Once the goal dose of 
Omegaven® was reached, the direct bilirubin declined and normalized.  His AST also 
normalized and he was removed from the liver-small bowel transplant list. Weekly CRP 
levels were obtained to monitor systemic inflammation. CRP levels decreased from a 
high of 1.85 to 0.17 mg/dL (Normal <0.5). He continues to receive Omegaven® at a dose 
1g/kg/day and has had no evidence of bleeding or clinical evidence of essential fatty acid 
deficiency. His direct bilirubin continues to be within the normal range and he has no 
evidence of jaundice. He is still receiving approximately 50% of his total caloric needs 
via the parenteral route. He continues to grow and is achieving his developmental 
milestones appropriately. This child has been on Omegaven® for greater than 5 years. 
 
Since the time of this initial patient, an additional 130 patients have been treated with 
Omegaven® at Children’s Hospital of Boston.  In addition to the aforementioned patient, 
24 children are receiving Omegaven® at home in conjunction with home parenteral 
nutrition. As of January 6, 2006, no patients from Children’s Hospital of Boston 
receiving Omegaven® have died of PN associated liver disease or required a liver 
transplant. 
 
In a recent article by Lee et al, entitled “Impact of fish oil-based lipid emulsion on serum 
triglyceride, bilirubin, and albumin levels in children with parenteral nutrition-
associated liver disease”, published in Pediatric Research (December, 2009), the authors 
demonstrated that substituting fish oil-based lipid emulsion for the standard soybean-
based emulsion will result in normalizing, to some degree, the altered physiologic 
balance that comes to exist in patients dependent on PN.  The indices that have shown 
improvement were decreasing direct bilirubin and triglyceride levels and increasing 
albumin levels.  In previous publications, these authors have also noted that the provision 
of fish-oil-based fat emulsion was not associated with essential fatty acid deficiency, 
hypertriglyceridemia, coagulopathy, infections, or growth delay. 
 
Researchers at The Hospital for Sick Children, Toronto, Canada published their findings 
of their experience with Omegaven® in young children in a recent publication (February, 
2009) The median age was 7.5 (range 3.6-46) months, and median parenteral nutrition 
duration before starting Omegaven® was 28.4 (range 15.3-55.3) weeks. Median initial 
serum conjugated bilirubin was 137 (range 54-203) micromole/L (8.06 [3.18-11.94] 
mg/dL). Nine of the twelve patients had complete and sustained resolution of 
hyperbilirubinemia within a median of 24 (range 7-37) weeks, and all were no longer 
being considered for liver transplantation. Improvements in markers of hepatic 
inflammation as well as nutritional status also were noted in these patients. Three of the 
12 patients received a liver-intestine transplant while taking Omegaven®. There were no 
complications attributable to Omegaven®.  


 
- 9 - 
 
                           
Patient Information 
DESIGN AND METHODS 
Study Design 
This phase II clinical trial will be a non-randomized, open-labeled, prospective study of 
intravenously administered Omegaven® fat emulsion in the treatment of PN associated 
liver injury. 
 
Patient Selection and Inclusion/Exclusion Criteria 
After the diagnosis of PN liver injury is made, patients who are followed by the 
Neonatology, Gastroenterology, Surgery, or the Critical Care Service in conjunction with 
the patient's primary physician will contact Drs. Caicedo, Chiu, or Lessaris, and an 
evaluation will be performed. If the patient's parents or guardians agree to participate in 
the study, informed consent will be obtained. The history of present illness and past 
medical history will be reviewed with the guardian and pertinent demographic and 
medical information will be recorded on data collection forms. These forms will be used 
to record all laboratory results, nutritional history, and descriptions of any liver biopsies 
performed.  
 
Though most patients receiving parenteral nutrition do not develop end stage liver 
disease, there is a small percentage of patients, typically infants and children on 
prolonged courses of parenteral nutrition, who do go on to develop fulminant liver 
failure.  The study population of this protocol is limited to patients felt to fulfill the 
following conditions:  
 
a) The patient will be PN-dependent (unable to meet nutritional needs solely by enteral 
nutrition) and  
b) The patient will have significant hepatic dysfunction due to PN despite utilization of 
all conventional therapies (the patient must have failed standard therapies to prevent the 
progression of his/her liver disease including surgical treatment, cycling of PN, 
reduction/removal of copper and manganese from PN, advancement of enteral feeding, 
and the use of ursodiol). 
 
Inclusion Criteria: 
 
1. Children 0-18 years of age 
2. Patients will be PN-dependent and expected to continue PN for at least 30 days 
3. Patients considered eligible for study participation must have PN-associated liver 
diseases . Other causes of liver disease (i.e., biliary atresia, galactosemia, alpha-1 
antitrypsin deficiency) will be excluded. A liver biopsy is not necessary for treatment 
4. Direct bilirubin > 2.0 mg/dl 
5. Signed patient informed consent 
6. Signed patient assent where applicable. 
 
The patient will be hospitalized at the time of enrollment and initiation of Omegaven®. 
 
 
 


 
- 10 - 
 
                           
Patient Information 
Exclusion Criteria: 
 
1. Pregnancy 
2. Other causes of chronic liver disease (cystic fibrosis, biliary atresia, alpha-1 
antitrypsin deficiency) 
3. Signs of advanced liver disease including cirrhosis on biopsy, varices, ascites 
4. The patient is allergic to eggs/shellfish 
5. The patient has a severe hemorrhagic disorder 
6. The patient is enrolled in any other clinical trial involving an investigational agent  
(unless approved by the designated physicians on the multidisciplinary team) 
7. The parent or guardian or child unwilling to provide consent or assent. 
 
Screening Procedures 
 
Prior historical and physical information, imaging studies, biopsies, and other available 
specialized tests will be reviewed by the multidisciplinary team experienced in the 
diagnosis and treatment of parenteral nutrition associated liver disease. Additional 
biochemical monitoring will be perfomed as necessary. If the patient’s status supports 
consideration of treatment, the option for non-experimental therapy will be investigated.  
 
Recruitment Methods 
With an anticipated enrollment of 3-5 patients per year, 20-25 patients will be recruited 
over the course of the 5 year study.   
Patients in the trial will be recruited from the NICU, PICU, CVICU, surgery, 
gastroenterology, and general pediatrics services at Levine Children's Hospital (LCH). 
Approximately 5-8 patients/year are diagnosed with severe PN associated liver injury at 
Levine Children’s Hospital.  The Principal Investigator (Dr. Caicedo) or Co-investigators 
(Dr. Chiu, Dr. Lessaris) will discuss treatment options including study treatment with the 
parents or legal guardians.  Informed consent for participation in the study will only be 
obtained by physicians who are able to fully inform the patients of alternatives to 
participation.   If the patient is a minor but of sufficient age and understanding, patient 
assent will also be obtained. 
 
Description of Study Treatments or Exposures/Predictors 
Bottles containing 50mL or 100 mL of 10% Omegaven® will be purchased from 
International Pharmacy of Hamburg, Germany. Insurance companies will be billed the 
cost of Omegaven®.  If the insurance company does not provide payment, Healthy @ 
Home, LLC will cover all drug costs for patients enrolled in this protocol. Omegaven® is 
manufactured by Fresenius Kabi AG, Bad Homburg, Germany. Omegaven® is 
formulated as an emulsion from fish oils.  
 
While inpatient, the emulsion for each patient will be provided in its original container 
for volumes more than 96 ml/day.  Doses less than 96 ml/day will be repacked into 
syringes to allow for administration via syringe pump.  If patients are to be discharged 
home on Omegaven®, all doses will be administered from the original manufacturer’s 
container. 


 
- 11 - 
 
                           
Patient Information 
 
Outpatients will have laboratory data monitored (Table 2) as do inpatients, with values 
reported to the pediatric gastroenterologists via the Pediatric Nutrition Support Clinic at 
the Levine Children’s Specialty Center.  Growth will be tracked weekly.  Home health 
nursing staff and guardians will be educated regarding Omegaven® and administration 
while the child is still an inpatient prior to discharge.  This education will include 
Omegaven® adverse event monitoring (Table 3) and reporting; administration practices; 
and information regarding monthly or other mutually agreed upon schedules for clinical 
evaluation and follow up of the patient by study investigators. 
 
All study materials will be stored securely until the time of administration. The bottles 
will be stored at room temperature below 30° C (do not freeze). Damaged or suspect drug 
will be returned unused to Fresenius- Kabi. Containers should be shaken before use. 
 
All supplies for the study protocol will be accompanied by accountability and shipping 
documents and will be maintained by the Investigator or deputy (e.g. research 
pharmacist). Information recorded on these accountability and shipping documents will 
include relevant dates, batch numbers, quantities received or dispensed, to whom 
dispensed, returned drug and drug lost or damaged.  
At the end of the protocol study, all used and unused Omegaven® will be accounted for.  
If expired, the remaining drug supplies will be destroyed. 
 
Financial Consideration 
A request to charge for Omegaven® has been submitted to the FDA.   Healthy @ Home, 
LLC will assume all costs, in the event that third party payers do not cover the cost of 
Omegaven®.   Study investigators will not receive financial benefit in any form from this 
research study. 
 
Details of Omegaven® Administration 
After baseline labs are obtained (Table II), therapy with Omegaven® will be initiated at a 
starting dose of 0.5gm/kg/day infused over 12-24 hours. After two days, the dose will be 
increased to 1 gm/kg/day, the goal dose. Omegaven® will be infused intravenously 
through either a central or peripheral catheter in conjunction with parenteral nutrition.   
The same standards of care provided to all patients receiving parenteral nutrition solution 
will be followed.  Laboratory tests will be performed as detailed in Table 2.  Growth will 
be tracked weekly.  If additional fat calories are needed, they will be provided via the 
enteral route.  
 
In the event that a patient is unable to achieve adequate calories parenterally and is 
unable to tolerate enteral feeds, it may be necessary to evaluate whether or not the patient 
should continue the study with Omegaven® as monotherapy or resume therapy with 
conventional fat emulsions at 1 gm/kg in addition to the Omegaven® so that additional 
parenteral fat calories can be given. The clinical team, in conjunction with the patient's 
primary physician, will determine if the patient should be removed from the protocol. 
 


 
- 12 - 
 
                           
Patient Information 
As previously mentioned, Omegaven® may be infused in the same manner as 
conventional fat emulsions through either a central or peripheral line. The emulsion is 
isotonic. It is compatible with parenteral nutrition solutions and may be co-infused via y-
site. Omegaven® may be infused through a 1.2micron inline filter. 
 
Dose Modification 
Hypertriglyceridemia: 
If hypertriglyceridemia develops, defined as serum triglyceride levels > 200 mg/dL, the 
following will be considered prior to reducing the dose: 
 
a) If the level was obtained while the patient was receiving a continuous 24- hour 
infusion of Omegaven®, the total dose should be infused over 20 hours, and a 
repeat serum triglyceride level obtained prior to resuming the infusion 4 hours later. 
 
b) Other sources of hypertriglyceridemia should be considered and addressed (drugs, 
renal disease) 
 
If necessary, if the triglycerides continue to remain high despite the aforementioned 
interventions, a dosage reduction of 25% will be considered. 
 
Hyperglycemia: 
If hyperglycemia develops, defined as serum glucose levels >250mg/dL, other sources of 
hyperglycemia should be considered and addressed (sepsis).  A minimum dosage 
reduction of 25% will occur.  Blood sugars will continue to be monitored closely with 
additional adjustments as warranted. 
 
Coagulopathy: 
Other sources of coagulopathy should be considered and addressed (sepsis, worsening 
liver failure).  Omegaven administration will be reduced or halted.  Coagulation profiles 
will continue to be monitored closely with additional adjustments as warranted. 
 
Duration of Therapy 
Patients will complete the study when he/she is completely off PN; develops a 
contraindication for further use; or the patient/family requests to be removed from the 
study protocol.  
 
In the event that a patient who has been listed for a liver or liver/intestinal transplant has 
an organ become available, the participation in this protocol will not preclude them from 
receiving the transplant. Omegaven® will not be administered post transplant. 
 
In the event that a patient whose hepatic enzymes and serum bilirubin have normalized 
still requires parenteral fat emulsion after receiving Omegaven® for more than 6 months, 
their clinical course will be reviewed, and a decision will be made whether to continue 
the Omegaven® or rechallenge the patient with conventional therapy (Intralipid®). 
 


 
- 13 - 
 
                           
Patient Information 
 
 
 
Discontinuation of Therapy 
Patients will continue to be followed by the Nutritional Support Program (LCH Division 
of Gastroenterology) upon discontinuation of therapy with Omegaven® a minimum of 3 
months after the treatment is stopped.  In addition, patients will be contacted annually for 
5 years following completion of the study, to ascertain growth, well being and PN 
dependency. 
 
Resumption of Therapy 
In the event that a patient who has been off the protocol more than 3 months must receive 
intravenous fat emulsion, treatment with Omegaven® will resume only if the patient 
shows evidence of PN liver disease (elevations in direct bilirubin > 2 or pathology 
findings consistent with cholestasis). Otherwise, the patient will be treated with 
conventional lipid emulsion. 
 
Definition of Primary and Secondary Outcomes/Endpoints 
The primary outcome is normalization of direct bilirubin to less than 0.4mg/dL by 9 
months. 
Seconday outcomes include: 
• Omegaven® will prevent EFA deficiency as evidenced by normal EFA profiles 
on monthly evaluations 
• The rate of triglyceride levels > 400 mg/dL with Omegaven® will be similar to 
that seen with PN administered with soy oil IFE (conventional emulsion, i.e., 
Intralipid®) as evidenced by baseline data and then weekly and monthly 
evaluations 
• PN containing Omegaven® will be safe for patients with respect to the risk of 
unexpected bleeding/coagulopathies as evidenced by weekly and monthly 
evaluations 
 
Data Collection Methods/Assessment and Schedules 
Data will be collected by the PI and the co-investigators. Hospital charts will be reviewed 
for pertinent clinical information. Results of liver biopsies and blood chemistries will be 
obtained from the Cerner Power Chart computer system.  Specifically, the history of 
present illness, past medical history, and birth history, pertinent physical exam findings 
including patient weight, the results of liver biopsies, and parenteral and enteral feeding 
history will be collected. The information will be recorded on hard copy data collection 
forms. 
 
Study Protocol Timeline 
This study protocol will end five years following commencement of the study. 
 
Adverse Event Criteria and Reporting Procedures 
Adverse events (AEs) will be assessed from the time of the first Omegaven® infusion 
until exit from the study. In particular, the patient will be observed during and shortly 


 
- 14 - 
 
                           
Patient Information 
after Omegaven® administration for the occurrence of anaphylactic or allergic reactions.  
Patients experiencing any adverse events that are moderate or severe in nature and that 
may be related to Omegaven® will have their treatment temporarily halted until the 
adverse event has resolved. Dose modifications in the event of hypertriglyceridemia, 
hyperglycemia and coagulopathy will occur as described above. Should patients be dose 
reduced for adverse events that are later considered to be unrelated to the study 
medication, treatment will recommence at the dose they had received prior to the dose 
reduction. Patients with anaphylactic or allergic reactions will not continue Omegaven® 
treatment. 
 
Any serious or unsuspected adverse events will be reported to the Institutional Review 
Board and to the FDA within 72 hours of the occurrence, or immediately if the event is 
fatal or life threatening as per CHS IRB Policy on Adverse and Unexpected Events and 
Unanticipated Risks to Research Subjects and Others. This will be done in person or by 
telephone, and by completion of the IRB form for adverse/unexpected event reporting. 
 
Unanticipated adverse events will be detected by the monitoring of vital signs, physical 
exams and laboratory analysis for all participants, as well as by observation by the 
nursing staff and guardians (following instruction) if participant is an outpatient. Events 
will be reported to the investigators immediately by telephone or pager, and subsequently 
to the appropriate board or committee. 
 
The IRB will be responsible for assuring that adverse event reporting requirements are 
met. Any patients who have agreed to participate in the study protocol, but who have not 
yet undergone intervention, will be informed of the adverse event.  
 
All AEs will be assessed by the Investigator and recorded in a case report form, inclusive 
of the date of onset and resolution; severity; relationship to study medication; outcome 
and action taken with the study medication.  In addition, the clinical severity of all AEs 
will be recorded and graded using the standard definitions of mild, moderate, severe or 
potentially life threatening with serious adverse events (SAE) deemed to be those severe 
to potentially life threatening (Table 3).  Once an AE or SAE is identified, research team 
members will ensure that the participants receive appropriate care and that all actions 
taken by the PI after observing the AE or SAE are documented.  In addition, all AE or 
SAEs will be classified and documented by the Investigator as definitely, probably, 
possibly, or probably unrelated to administration of study drug.   
 
Patients will be withdrawn from the study for any of the following: 
 
a) Toxicity considered unacceptable by the Investigator  
        note: no adverse effects have been observed in patients receiving Omegaven® that  
 
could be attributed to its use  
b) Patient/guardian requests to discontinue treatment and/or observation for any reason 
c)   A suitable organ has been located and the patient is able to undergo a liver or 
 
liver/intestinal transplant 
d) Decision by the Investigator that termination is in the patient’s best medical interest 


 
- 15 - 
 
                           
Patient Information 
e) Patient is lost to follow-up. 
 
In the event that a patient is withdrawn, the Investigator will document the date of 
withdrawal, the reason for withdrawal, and the results of all assessments made up to the 
date of withdrawal. 
 
 
DATA MANAGEMENT AND STATISTICAL ANALYLSIS 
 
Data Management Methods 
Overview 
 
This phase II clinical trial study will be supported by an Access-based data management 
system (DMS). The system will include a protocol management system that assists study 
staff with accurate collection of study data and monitors protocol adherence. The system 
will provide and be linked to a data entry system. Features of the system include double 
data entry, data range and logic checks, cross form validations at the time of data entry 
and audit trails of entered and corrected data. 
 
Protocol Management and Protocol Status 
 
All study related tasks will follow Good Clinical Practice Guidelines. Protocol status 
reports from the protocol management system will allow the principal investigator to 
monitor protocol adherence on a regular basis.  
 
Data Entry and Databases 
 
Study results will be entered into the DMS from paper based case report forms that will 
be completed by the investigators. 
 
Confidentiality, Security, Back-Up 
The databases will be located on the CHS Network and therefore backed - up on a daily 
basis. All study files will be password protected to ensure patient confidentiality and 
security of the database. 
 
Quality Control Methods 
Dispensing of Study Drug 
 
Pharmacy dispensing records will be reviewed by a study monitor on a monthly basis to 
ensure adherence with procedures for dispensing of Omegaven. 
 
Legal and Ethics Requirements 
 
This study is being conducted under a FDA Investigational New Drug Application. FDA 
guidelines must be followed. Federal regulations require all investigational studies be 
conducted under the auspices of an IRB, as defined in the Code of Federal Regulations, 


 
- 16 - 
 
                           
Patient Information 
Title 21, Part 56; and in accordance with the Declaration of Helsinki (1964) amended 
Edinburgh, Scotland (2000). The IRB will approve all aspects of the study, including the 
protocol and informed consent to be used and any modifications made to the protocol or 
informed consent prior to the initiation of the study. All changes to the protocol or 
consent form must be reviewed and approved prior to implementation, except where 
necessary to eliminate apparent immediate hazards to human subjects. 
 
Informed Consent 
 
The Investigator will be responsible for obtaining an Informed Consent signed by each 
patient or his/her legally authorized representative prior to his/her participation in the 
study in accordance with the Code of Federal Regulations, Title 21, Part 50.20. Informed 
Consent will be obtained from a patient or his/her legally authorized representative after a 
full explanation of the purpose of the study, the risks and discomforts involved, potential 
benefits, etc. have been provided by the Investigator or designee, both verbally and in 
writing. The original of the signed consent must be maintained in the patient’s medical 
record. The person who signed the consent must also be given a copy of the signed 
consent form. 
 
Patient Confidentiality 
 
Individual patient medical information obtained as a result of this study is considered 
confidential, and disclosure to third parties, other than those cited below, is prohibited. 
Patient confidentiality will be further ensured by utilizing patient identification code 
numbers and patient initials. Data generated as a result of this study will be available for 
inspection, on request by various regulatory agencies. These shall include all study-
relevant documentation, including medical histories to verify eligibility, laboratory test 
results to verify transcription accuracy, treatment and diagnostic reports, 
admission/discharge summaries for hospital admissions occurring while the patient is on 
study, and autopsy reports (if available) for deaths occurring during or in temporal 
proximity to the study. 
 
As part of the required content of the informed consent, patients must be informed that 
their records will be reviewed by various regulatory agencies.  
 
Retention of Records 
 
The Principal Investigator and study staff will maintain a comprehensive and centralized 
filing system of all study related documentation which is suitable for inspection at any 
time by various regulatory agencies.  These include: 
 
a. 
Patient files including source documentation and Informed Consent 
b. 
Study files, including the protocol with all amendments, copies of all regulatory  
 
documentation, and all correspondence with the FDA and IRB 
c. 
Pharmacy files including drug shipment, dispensing, and accountability records,  
 
and pharmacy-related correspondence 


 
- 17 - 
 
                           
Patient Information 
 
Per FDA regulations, the Primary Investigator will retain records for a period of two (2) 
years following discontinuation of the study. 
 
Data Analysis Plan 
The study protocol is intended to evaluate the safety and efficacy of Omegaven® in the 
treatment of PN induced liver injury.  Safety is addressed in the Data and Safety 
Monitoring Plan. Serum markers for efficacy will be monitored (bilirubin and liver 
enzymes). The specific data analysis will be evaluated by our statistician. 
 
Statistical Power and Sample Considerations 
As discussed above, this study protocol is not intended to prove statistical significance. 
 
Study Organization 
Dr. Caicedo will serve as the principal investigator. The investigators will perform all 
data collection and data entry. Drs. Chiu and Lessaris will assist with patient enrollment.  
Drs. Caicedo, Chiu and Lessaris will assist in study design and data analysis. 
 
Data and Safety Monitoring Plan 
Monitoring for toxicity due to Omegaven will be assessed by analyzing clinical and 
laboratory parameters including serum electrolytes, hematological studies, serum 
triglycerides, total cholesterol, essential fatty acid profiles, blood and urine glucose and 
liver and renal function tests. Blood samples will be taken prior to the start of therapy, 
and weekly thereafter until direct bilirubin <2mg/dL.  Subsequent testing will be 
determined based on direct bilirubin values (as this is the monitoring standard of care for 
liver failure) and will be bimonthly or monthly.  See Table 2 for additional information. 
Dose reduction will occur if there is evidence of hypertriglyceridemia (serum 
triglycerides > 200mg/dL), hyperglycemia (serum glucose >250mg/dL), or evidence of 
bleeding. Growth indices including weight, length/height, and head circumference will 
also be monitored.   Dr. Pineiro, the director of Pediatric Gastroenterology at LCH will be 
the Data and Safety Monitor.  He will review patient data quarterly to ensure patient 
safety is upheld and that protocols are followed as described.  The study will be halted in 
the event of one life threatening episode related to Omegaven® administration. 
 
RSKS AND DISCOMFORTS 
Description of Risks and Discomforts 
 
Potential Risk of Omegaven® Treatment 
 
Omegaven® has been studied in animal pre-clinical models as well as Phase I, II, III, and 
post marketing human trials in both Europe and Asia.  Prolonged bleeding time and an 
inhibited platelet aggregation can occur. It should not be administered to patients known 
to be allergic to fish or egg protein.  
 
Contraindications to Omegaven® include the following: 
 


 
- 18 - 
 
                           
Patient Information 
Impaired lipid metabolism 
 
Severe hemorrhagic disorders 
Unstable diabetes mellitus 
Collapse and shock 
Stroke/ Embolism 
Recent cardiac infarction 
 
Undefined coma status 
Known allergy to fish or egg protein 
 
Side effects: 
 
The infusion of Omegaven® can lead to a prolonged bleeding time and an inhibited 
platelet aggregation. In rare cases, patients may experience a fishy taste. 
 
The administration of Omegaven® should be stopped or reduced if there is a marked 
increased in blood glucose levels during the Omegaven® infusion. Undesirable effects 
that are seen during the infusion of Omegaven® that may also occur with conventional 
fat emulsions (i.e., Intralipid®) include: 
 
Slight rise in body temperature 
 
Heat sensation and/or cold sensation 
Chills 
Flushing or cyanosis 
Lack of appetite, nausea, vomiting 
 
Dyspnea 
Headache, pain in the chest, bone pain 
Priapism 
Increase/decrease blood pressure 
Anaphylactic reactions/erythema 
 
Overdose: 
 
In the event of an overdose of Omegaven®, there is a risk of developing fat overload 
syndrome that may occur when the triglyceride level rises >200 mg/dL acutely as a result 
of too rapid a rate of infusion, or chronically at high infusion rates in associated with a 
change in the patient’s clinical condition (e.g., renal dysfunction, sepsis).  In such cases, 
the infusion should be stopped or, if necessary, continued at a reduced dose.  
 
Metabolic acidosis has occurred in patients receiving Omegaven® at excessive doses 
without simultaneous administration of dextrose. 
 
Potential Benefit of Omegaven® Treatment 
 
Omegaven® may be effective in stabilizing or reversing hepatic injury associated with 
the use of parenteral nutrition. It may allow the patient to continue to receive the majority 


 
- 19 - 
 
                           
Patient Information 
of his/her caloric intake from parenteral nutrition while advancing on enteral nutrition or 
awaiting liver or liver/intestinal transplant. 
 
Potential Risks of No Treatment 
 
Since Omegaven® will only be offered to those patients for whom no standard therapy is 
likely to be safe and effective, the risks of not being treated are those allowing for the 
natural history of their disease and associated clinical manifestations to progress. These 
include fulminant liver failure and death. 
 
Summary – Overall Risk Assessment 
 
Patients will be at some risk inherent in taking a pharmaceutical agent that has not been 
fully evaluated for long duration treatment. However, the availability of safety data 
demonstrates no life-threatening risks or toxicities to vital organs or physiologic 
functions. Prolonged bleeding times and inhibition of platelet aggregation are a potential 
risk, especially to those patients with an underlying coagulopathy or those being treated 
with an anticoagulant. The potential benefits of Omegaven® in this patient population are 
mainly based on the experimental evidence; a highlighted case of dramatic success; and 
success in phase I clinical trials. However, the study will only be available to those for 
whom no standard therapy is available or appropriate, or has already failed. The risks and 
potential benefits will require careful individual assessment by both the investigators and 
patients.  The heterogeneity of clinical manifestations will lead to non-uniform risk-
benefit ratios across the eligible patient population. 
 
Privacy Provisions 
Individual patient medical information obtained as a result of this study protocol is 
considered confidential and disclosure to third parties, other than those cited below, is 
prohibited. Patient confidentiality will be further ensured by utilizing initials. Data 
generated as a result of this study will be available for inspection, on request by various 
regulatory agencies. These shall include all study-relevant documentation, including 
medical histories to verify eligibility, laboratory test results to verify transcription 
accuracy, treatment and diagnostic reports, admission/discharge summaries for hospital 
admissions occurring while the patient is on study, and autopsy reports (if available) for 
deaths occurring during or in temporal proximity to the study. 
 
Confidentiality Provisions 
Loss of patient confidentiality is another risk in this study. The risk of loss of 
confidentiality will be reduced by the study database being password protected and the 
use of initials as patient identifiers. 
 
POTENTIAL BENEFITS 
 
The potential benefits of this study protocol apply directly to those seen in phase I 
clinical trials and to possible improvement in the treatment of future patients. If 
successful, the  experimental treatment will provide a safe and effective means of 


 
- 20 - 
 
                           
Patient Information 
avoiding liver failure requiring transplant or that may  lead to death.  Thus, the potenital 
complications of surgery or fulminant hepatic failure may be avoided.  
 
PN associated liver disease is a life threatening condition . Available therapies 
(liver/small bowel transplant, intestinal lengthening, ursodiol, combination 
enteral/parenteral feedings) are often inadequate or entail high risks.  Phytosterol-based 
intravenous fat emulsions containing large quantities of omega 6 fatty acids have been 
associated with PN associated liver disease. For example, one patient, with bridging 
fibrosis secondary to prolonged PN/lipid therapy, treated with Omegaven® has had a 
sustained dramatic response with resolution of jaundice and direct bilirubin levels < 2. 
The safety profile of Omegaven® has been demonstrated to be acceptable for the diseases 
treated and should be considered as an option for patients requiring a form of intravenous 
fat emulsion. 
 
REFERENCES 
1.  Dudrick SJ, Wilmore DW, Vars HM, Rhoads JE. Long-term total parenteral nutrition 
with growth, development, and positive nitrogen balance. Surgery 1968;64:134-42. 
2.  Wilmore DW, Dudrick SJ. Growth and development of an infant receiving all 
nutrients exclusively by vein. Jama 1968;203:860-4. 
3.  Mullick FG, Moran CA, Ishak KG. Total parenteral nutrition: a histopathologic 
analysis of the liver changes in 20 children. Mod Pathol 1994;7:190-4. 
4.  Freund HR. Abnormalities of liver function and hepatic damage associated with total 
parenteral nutrition. Nutrition 1991;7:1-5; discussion 5-6. 
5.  Beath SV, Davies P, Papadopoulou A, Khan AR, Buick RG, Corkery JJ, Gornall P, 
Booth IW. Parenteral nutrition-related cholestasis in postsurgical neonates: multivariate 
analysis of risk factors. J Pediatr Surg 1996;31:604-6. 
6.  Greenberg GR, Wolman SL, Christofides ND, Bloom SR, Jeejeebhoy KN. Effect of 
total parenteral nutrition on gut hormone release in humans. Gastroenterology 
1981;80:988-93. 
7.  Yeh SL, Chen WJ, Huang PC. Effects of L-glutamine on induced hepatosteatosis in 
rats receiving total parenteral nutrition. J Formos Med Assoc 1995;94:593-9. 
8.  Kubota A, Yonekura T, Hoki M, Oyanagi H, Kawahara H, Yagi M, Imura K, Iiboshi 
Y, Wasa K, Kamata S, Okada A. Total parenteral nutrition-associated intrahepatic 
cholestasis in infants: 25 years' experience. J Pediatr Surg 2000;35:1049-51. 
9.  Moss RL, Das JB, Ansari G, Raffensperger JG. Hepatobiliary dysfunction during total 
parenteral nutrition is caused by infusate, not the route of administration. J Pediatr Surg 
1993;28:391-6; discussion 396-7. 
10. Helms RA, Christensen ML, Mauer EC, Storm MC. Comparison of a pediatric versus 
standard amino acid formulation in preterm neonates requiring parenteral nutrition. J 
Pediatr 1987;110:466-70. 
11. Moss RL, Haynes AL, Pastuszyn A, Glew RH. Methionine infusion reproduces liver 
injury of parenteral nutrition cholestasis. Pediatr Res 1999;45:664-8. 
12. Meehan JJ, Georgeson KE. Prevention of liver failure in parenteral nutrition-
dependent children with short bowel syndrome. J Pediatr Surg 1997;32:473-5. 
13. Whalen GF, Shamberger RC, Perez-Atayde A, Folkman J. A proposed cause for the 
hepatic dysfunction associated with parenteral nutrition. J Pediatr Surg 1990;25:622-6. 


 
- 21 - 
 
                           
Patient Information 
14. Zamir O, Nussbaum MS, Bhadra S, Subbiah MT, Rafferty JF, Fischer JE. Effect of 
enteral feeding on hepatic steatosis induced by total parenteral nutrition. JPEN J Parenter 
Enteral Nutr 1994;18:20-5. 
15. Kaminski DL, Adams A, Jellinek M. The effect of hyperalimentation on hepatic lipid 
content and lipogenic enzyme activity in rats and man. Surgery 1980;88:93-100. 
16. Hultin M, Carneheim C, Rosenqvist K, Olivecrona T. Intravenous lipid emulsions: 
removal mechanisms as compared to chylomicrons. J Lipid Res 1995;36:2174-84. 
17. Qi K, Al-Haideri M, Seo T, Carpentier YA, Deckelbaum RJ. Effects of particle size 
on blood clearance and tissue uptake of lipid emulsions with different triglyceride 
compositions. JPEN J Parenter Enteral Nutr 2003;27:58-64. 
18. Nestel PJ. Effects of N-3 fatty acids on lipid metabolism. Annu Rev Nutr 
1990;10:149-67. 
19. Chen W. Effects of fat emulsions with different fatty acid composition on plasma and 
hepatic lipids in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:24. 
20.  Yeh S. Effects of fish oil and safflower oil emulsions on diet-induced hepatic 
steatosis in rats receiving total parenteral nutrition. Clinical Nutrition 1996;15:80. 
21. Kinsella JE, Lokesh B, Broughton S, Whelan J. Dietary polyunsaturated fatty acids 
and eicosanoids: potential effects on the modulation of inflammatory and immune cells: 
an overview. Nutrition 1990;6:24-44; discussion 59-62. 
22. Alwayn IPJ, Gura K, Nose V, Zausche B, Javid P, Garza J, Verbesey J, Voss S, 
Ollero M, Andersson C, Bistrian B, Folkman J, Puder M. Omega-3 fatty acid 
supplementation prevents hepatic steatosis in a murine model of nonalcoholic fatty liver 
disease. Pediatr Res. 2005 Mar;57(3):445-52. Epub 2005 Jan 19.  
23.Van Aerde JE, Duerksen DR, Gramlich L, Meddings JB, Chan G, Thomson AB, 
Clandinin MT 1999 Intravenous fish oil emulsion attenuates total parenteral nutrition-
induced cholestasis in newborn piglets. Pediatr Res 45:202-208. 
24. Morlion BJ, Torwesten E, Lessire Al, et al. The effect of parenteral fish oil n 
leukocyte membrane fatty acid composition and leukotriene synthesizing capacity in 
postoperative trauma. Metabolism 1996; 45:1208-1213. 
25. Grimminger F, Führer D, Papavassilis C, et al. Influence of intravenous n-3 liipid 
supplementation on fatty acid profiles and lipid mediator generation in patients with 
severe ulcerative colitis. Eur J Clin Invest 1993; 23:706-15. 
26. Grimminger F, Mayser P, Papavassilis C, et al. A double blind randomized, placebo-
controlled trial on n-3 fatty cid based lipid infusion in acute, extended guttate psoriasis. 
Rapid improvement of clinical manifestations and changes in neutrophil leukotriene 
profile. Clin Invest 1993; 7:634-43. 
27. Mayeser P, Mrowietz U, Arenberger P, et al. ω-3 fatty acid  based lipid emulsion in 
patients with chronic plaque psoriasis. J Am Acad Dermatol 1998; 38:539-47.  
28. Heller AR, Fischer S, Rössel T, Impact of n-3 fatty acid supplemented parenteral 
nutrition on haemostasis patterns after major abdominal surgery. Br J  Nutr 2002; 87; 
Suppl 1:95-101. 
29. Kolezko BV, Fürst P. Fish oil in parenteral nutrition in infants: clinical evidence and 
experience. Data on file, Fresenius- Kabi AG, Bad Homburg v.d.h. 
30. Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, 
Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion in the 


 
- 22 - 
 
                           
Patient Information 
treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar; 
121(3):e678-86.  
31. Diamond IR, Sterescu A, Pencharz PB, Kim JH, Wales PW. Changing the paradigm: 
omegaven for the treatment of liver failure in pediatric short bowel syndrome. J Pediatr 
Gastroenterol Nutr. 2009 Feb; 48(2):209-15.  
32.  Gura KM, Parsons SK, Bechard LJ, Henderson T, Dorsey M, Phipatanakul W, 
Duggan CP, Puder M Lenders C.  Use of a fish oil-based lipid emulsion to treat essential 
fatty acid deficiency in a soy allergic patient receiving parenteral nutrition. Clinical 
Nutrition. 2005 Oct;24(5):839-47. 
33. Lee, S, Valim, C, Johnston, P, Le, HD, Meisel, J, Arsenault, D, Gura, K, and Puder 
M.  Impact of Fish Oil-Based Lipid Emulsion on Serum Triglyceride, Bilirubin, and 
Albumin Levels in Children with Parenteral Nutrition-Associated Liver Disease. 
Pediatric Research. 2009 December, 66 (6): 698-703. 


 
- 23 - 
 
                           
Patient Information 
Table 1 
Comparison of Parenteral Fat Emulsions (10 grams fat/100 mL) 
OIL 
Intralipid® 
Liposyn® II 
Omegaven® 
Soybean 
10 
5 
 
Safflower 
 
5 
 
Fish 
 
 
10 
% FATS 
 
 
 
Linoleic 
50 
65 
0.1-0.7 
α-linolenic 
9 
4 
<0.2 
E.P.A. 
 
 
1.3-2.8 
D.H.A. 
 
 
1.4-3.1 
Arachidonic acid 
 
 
0.1 -0.4 
Glycerol 
2.3 
2.5 
2.5 
Egg Phospholipid 
1.2 
1.2 
1.2 
Available in the   
United States 
Yes 
Yes 
No 
 


 
- 24 - 
 
                           
Patient Information 
Table 3: 
Laboratory Monitoring Schedule for Omegaven® Therapy 
 
Laboratory test: 
Baseline 
(pre-
Omega-
ven®) 
Q  week* 
Until Direct  
Bilirubin  < 
2mg/dL 
Bimonthly * 
Until 
Direct  
Bilirubin <0.4 
mg/dL 
Monthly* once     
direct bilirubin   
<0.4 mg/dL 
 
 
 
 
 
Sodium 
X 
X 
X 
X 
Potassium 
X 
X 
X 
X 
Chloride 
X 
X 
X 
X 
Glucose 
X 
X 
X 
X 
BUN 
X 
X 
X 
X 
Creatinine 
X 
X 
X 
X 
Triglycerides 
X 
X 
X 
X 
Calcium 
X 
X 
X 
X 
Magnesium 
X 
X 
X 
X 
Phosphorus 
X 
X 
X 
X 
Prealbumin 
X 
X 
X 
X 
Albumin 
X 
X 
X 
X 
Total protein 
X 
X 
X 
X 
SGPT 
X 
X 
X 
X 
Alkaline phosphatase 
X 
X 
X 
X 
Bilirubin (total & direct) 
X 
X 
X 
X 
GGT 
X 
X 
X 
X 
AST 
X 
X 
X 
X 
Essential Fatty Acid 
Profile 
X 
X 
X 
X 
Free cholesterol 
X 
X 
X 
X 
Free fatty acids 
X 
X 
X 
X 
Lipid Panel 
X 
X 
X 
X 
Hemoglobin 
X 
X 
X 
X 
Hematocrit 
X 
X 
X 
X 
RBC 
X 
X 
X 
X 
WBC 
X 
X 
X 
X 
Platelets 
X 
X 
X 
X 
PT 
X 
X 
X 
X 
PTT 
X 
X 
X 
X 
INR 
X 
X 
X 
X 
Fibrinogen 
X 
X 
X 
X 
* Direct bilirubin evaluations guide further testing as this value is the standard of care for determining liver failure.  
more often as necessitated by clinical course; may be reduced in patients who are stable (i.e. outpatient) and whose 
biochemical markers have improved 
 


 
- 25 - 
 
                           
Patient Information 
 
 
Table 3: 
 
Omegaven® Possible Adverse Events 
 
CLINICAL 
GRADE I 
(MILD) 
GRADE II 
(MODERATE) 
GRADE III - SAE 
(SEVERE) 
GRADE IV - SAE 
(POTENTIALLY 
LIFE 
THREATENING/
DEATH) 
Phlebitis 
Hypotension 
Bowel obstruction 
Uncontrolled 
bleeding 
Fever 
Hypertension 
Sepsis syndrome 
Anaphylaxis 
Fishy taste 
Urinary tract 
infection 
 
Shock 
Chills 
Poor growth 
 
Death 
Flushing 
Priapism 
 
 
Cyanosis 
 
 
 
Nausea/Vomiting 
 
 
 
Dehydration 
 
 
 
Rash 
 
 
 
LABORATORY 
Hyperglycemia 
Anemia 
Sepsis 
Coagulopathy 
Hypertriglyceridemia Leukopenia 
 
 
Essential fatty acid 
deficiency 
Thrombocytopenia  
 
Electrolyte 
abnormalities 
Abnormal liver 
function tests 
 
 
 
Positive urine 
culture