Clinical trial NCT01325584
Conditions: Cancer Hepatic Injury
Sponsor: Midwestern Regional Medical Center
Start date: 2012-10-01; Completion date: 2017-04-01
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purposes of this study are to make Omegaven® available to cancer patients with liver disease and to determine if Omegaven® can improve or prevent further liver disease. The study will also look at the effects Omegaven® has on immune function.

Detailed description:
This compassionate use study will include patients with advanced cancer requiring PN for long-term nutrition support who have developed PN-induced hepatic injury or who have existing hepatic dysfunction. Therapy with Omegaven will be provided at an initial dose of 0.1 g/kg body weight (1ml/kg) and increased to 0.2 g/kg body weight (2ml/kg) on day 2 or 3 of treatment. For patients \> 120% ideal body weight, adjusted body weight will be used. The infusion rate will not exceed 0.5mL Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). Omegaven will be co-administered via a y-site infusion, with containers being changed every 12 hours. The patient may receive other lipids to meet Essential Fatty Acid (EFA) and/or additional calorie needs. Patients will receive the initial infusion of PN containing Omegaven at Midwestern Regional Medical Center (MRMC) in the infusion center to observe for adverse reactions. If an adverse reaction is observed, IV steroids \& benadryl will be administered \& Omegaven will be discontinued. Patients will continue to receive infusions at CTCA for the first 2 to 3 days of dosing. After tolerance is established, patients will receive treatment at home with Coram. All study patients will have a Screening Visit; Day 1, Day 2 and Day 3 visits; and weekly visits for one month (see Table 2).

Arms: arm 1: This is a compassionate use study. All participants will receive intravenous Omegaven (10% fish oil emulsion) with parenteral nutrition for 4 weeks.
Interventions: intervention 1: Omegaven
Intervention descriptions: intervention 1: initial dose of 0.1 g/kg body weight (1ml/kg) and increased to 0.2 g/kg body weight (2ml/kg) on day 2 or 3 of treatment. The infusion rate will not exceed 0.5mL Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). Patients will receive the initial infusion of PN containing Omegaven at Midwestern Regional Medical Center (MRMC) in the infusion center to observe for adverse reactions. Patients will continue to receive infusions at MRMC for the first 2 to 3 days of dosing. After tolerance is established, patients will receive treatment at home. All study patients will have a Screening Visit; Day 1, Day 2 and Day 3 visits; and weekly visits for one month.

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
 
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Confidentiality Statement 
This document is the confidential information of Cancer Treatment Centers of America. It is provided to you as an 
investigator or consultant for review by you, your personnel, and the applicable Institutional Review Board. Your 
acceptance of this document constitutes an agreement that you will not disclose the information contained herein 
to others without the prior written consent of Cancer Treatment Centers of America. 
Protocol Title: Compassionate Use of Omegaven® in the Treatment of Parenteral Nutrition Induced 
Hepatic Injury 
 
 
 
Principal-Investigator: 
 
 
 
 
 
 
Sub-Investigator: 
Pankaj Vashi, MD 
National Clinical Director of Gastroenterology/Nutrition and Metabolic Support 
Cancer Treatment Centers of America 
Midwestern Regional Medical Center 
2520 Elisha Avenue 
Zion, Illinois 60099 
Carolyn Lammersfeld, RD 
National Director of Nutrition 
Cancer Treatment Centers of America 
Midwestern Regional Medical Center 
2520 Elisha Avenue 
Zion, Illinois  60099 
Phone:  847-872-6328Fax:  847-872-6107Email:  Pankaj.Vashi@ctca-hope.com or 
Carolyn. Lammersfeld@ctca-hope.com 
Study Coordinators: 
Sadie Dahlk 
Cancer Treatment Centers of America 
Midwestern Regional Medical Center 
2520 Elisha Avenue 
Zion, Illinois 60099 
Phone:  847-872-6241 
Fax:  847-872-6107 
E-mail:  Sadie. Dahlk@ctca-hope.com 
 
Digant Gupta 
Cancer Treatment Centers of America 
2520 Elisha Avenue 
Zion, IL  60099 
Email:  gupta_digant@yahoo.com 
Study Product: 
Omegaven® 
 
 
IND Number: 
110,979 
  


 
 
 
 
 
 
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Protocol Synopsis 
 
PRINCIPAL-INVESTIGATORS:  Pankaj Vashi, MD, Cancer Treatment Centers of America & Carolyn Lammersfeld, RD, 
Cancer Treatment Centers of America 
TITLE OF THE STUDY:   Compassionate Use of Omegaven® in the Treatment of Parenteral Nutrition Induced Hepatic 
Injury 
STUDY MEDICATION:  Omegaven® 
INDICATION:  Parenteral Nutrition (PN) Induced Hepatic Injury 
STUDY PHASE:  Compassionate Use 
STUDY CENTER:  Cancer Treatment Centers of America (CTCA), Zion, Illinois 
NUMBER OF PATIENTS:  Approximately 30 patients will be included, with potential of including up to 50 patients 
depending on preliminary data 
STUDY PURPOSE OBJECTIVES: 
Primary: To examine whether Omegaven, an omega-3 based lipid emulsion, can improve or prevent further 
deterioration of PN-induced hepatic dysfunction 
Secondary: To examine the effects of Omegaven, an omega-3 based lipid emulsion, on immune function and 
markers of the inflammatory process 
STUDY DESIGN: 
Patients who have been receiving treatment at CTCA and have been receiving outpatient PN and develop PN-
induced hepatic injury, or will be starting home PN and have existing hepatic dysfunction. 
Patients will receive their initial infusion of PN containing Omegaven at a CTCA location to observe for adverse 
reactions.  Omegaven will be given on Day 1 at a dose of 0.1 g/kg body weight (1 mL/kg).  On Day 2 or 3, it will be 
increased to 0.2 g/kg body weight (2 mL/kg). The infusion rate will not exceed 0.5mL Omegaven/kg body weight/hr 
(corresponding to 0.05g fish oil/kg/hr). 
After tolerance is established, patients will have the option to receive treatment at home through Coram for 4 
weeks or until hepatic dysfunction is reversed (established normalization of liver function tests/serum bilirubin < 2).  
INCLUSION CRITERIA:   
A patient must meet the following criteria to participate in this study: 
I.1     Male or Female; ages 18 to 80 
I.2     Receiving treatment at CTCA 
I.3     Receiving PN (either in the infusion center or at home) 
I.4     Have existing hepatic dysfunction defined as Elevation of >3x the normal level of one or more of the 
         following:   Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), or Alanine Aminotransferase 
        (ALT) and/or Bilirubin > 2 mg/dl in the absence of biliary obstruction.  
I.5     Able to provide informed written consent (patient or legally acceptable representative) 
EXCLUSION CRITERIA:   
Patients will be excluded from participating in the study for the following reasons: 
E.1 
Hypertriglyceridemia (fasting triglycerides [TG] >  400) 
E.2 
Allergy to fish or egg protein 
E.3 
Currently on therapeutic doses of Coumadin, heparin, or low molecular weight heparin. 
E.4 
Hemodynamically unstable 
E.5 
Bilirubin > 5 mg/dL 
E.6 
Documented progression of liver metastases 
E.7 
Unstable diabetes with known diabetic ketoacidosis within 7 days of screening 
E.8 
Recent cardiac infarction taking plavix 
E.9 
Severe hemorrhagic disorders 


 
 
 
 
 
 
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E.10 Embolism 
E.11 Sepsis 
E.12 Undefined coma status 
E.13 Renal insufficiency with calculated creatinine clearance < 30 mL/min. 
E.14 Pregnancy or lactation 
TREATMENT: 
Treatment with Omegaven will be given on study Day 1 at a dose of 0.1 g/kg body weight (1 mL/kg).  On Day 2 or 3, 
it will be increased to 0.2 g/kg body weight (2 mL/kg).  The infusion rate will not exceed 0.5mL Omegaven/kg body 
weight/hr (corresponding to 0.05g fish oil/kg/hr).   
Omegaven will be co-infused via y-site.  Containers will be changed every 12 hours.  Omegaven will be given 
through a 1.2 micron inline filter. 
Omegaven will be given daily for: 
• 
Up to 4 weeks, or  
• 
Until normalization of alkaline phosphatase, AST, & ALT 
The patient may receive other lipids to meet essential fatty acid (EFA) and/or additional calorie needs. 
EFFICACY OUTCOME VARIABLES: 
• 
Maximum conjugated bilirubin 
• 
Time to resolution of bilirubin or death 
• 
Average improvement in bilirubin, alkaline phosphatase, AST, & ALT 
SAFETY OUTCOME VARIABLES: 
• 
Summary of laboratory results 
• 
Summary of AEs for each patient  
 
 


 
 
 
 
 
 
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Table of Contents 
1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................................................... 6 
2. 
INTRODUCTION ........................................................................................................................ 7 
2.1. 
Background .................................................................................................................................. 7 
2.2. 
Risk Category ................................................................................................................................ 8 
2.3. 
Rationale ...................................................................................................................................... 8 
2.4. 
Statement .................................................................................................................................... 8 
3. 
OBJECTIVES .............................................................................................................................. 8 
4. 
INVESTIGATONAL PLAN............................................................................................................ 9 
4.1. 
Study Design................................................................................................................................. 9 
4.2. 
Study Procedures by Visit .......................................................................................................... 10 
4.2.1. 
Screening Visit .............................................................................................................. 10 
4.2.2. 
Day 1 Visit ..................................................................................................................... 10 
4.2.3. 
Day 2/Day 3 Visit .......................................................................................................... 10 
4.2.4. 
Day 5 Visit ..................................................................................................................... 10 
4.2.5. 
Weekly Visits During Home Use of Omegaven (up to 4 weeks of treatment) ............. 11 
4.2.6. 
Final Study Visit/Early Withdrawal Visit ....................................................................... 11 
4.3. 
Description of Study-Specific Procedures .................................................................................. 11 
4.3.1. 
Diagnostic Tests ............................................................................................................ 11 
5. 
SELECTION AND WITHDRAWAL OF PATIENTS ....................................................................... 12 
5.1. 
Patient Inclusion Criteria ............................................................................................................ 12 
5.2. 
Patient Exclusion Criteria ........................................................................................................... 12 
5.3. 
Patient Withdrawal Criteria ....................................................................................................... 12 
6. 
CONCOMITANT MEDICATIONS/TREATMENT ........................................................................ 13 
7. 
COMPLIANCE .......................................................................................................................... 13 
8. 
INVESTIGATIONAL MATERIALS AND MANAGEMENT ............................................................ 13 
8.1. 
Investigational Product .............................................................................................................. 13 
8.1.1. 
General Investigational Product Information ............................................................... 13 
8.1.2. 
Dosing ........................................................................................................................... 14 
8.1.3. 
Dispensation ................................................................................................................. 14 
8.1.4. 
Storage and Handling ................................................................................................... 14 
8.1.5. 
Accountability ............................................................................................................... 14 
8.1.6. 
Dose Adjustments ........................................................................................................ 14 
9. 
ASSESSMENT OF EFFICACY AND SAFETY ................................................................................ 14 
9.1. 
Outcome Variables ..................................................................................................................... 14 
9.2. 
Adverse Event (AE) Recording/Reporting .................................................................................. 14 
9.3. 
Serious Adverse Event (SAE) Recording/Reporting ................................................................... 16 
9.4. 
IND Safety Reporting .................................................................................................................. 16 
9.4.1. 
Written IND Safety Report ........................................................................................... 17 
9.4.2. 
Telephone or Fax IND Safety Reports ........................................................................... 17 
9.5. 
IRB Safety Reporting .................................................................................................................. 17 
10. 
DATA MANAGEMENT ............................................................................................................. 17 
10.1. Data Management ..................................................................................................................... 17 
10.2. Sample Size Determination ........................................................................................................ 17 
10.3. Disposition and Baseline Assessment ........................................................................................ 17 
10.4. Outcomes Analysis ..................................................................................................................... 17 
10.5. Data Monitoring Committee ...................................................................................................... 18 
10.6. Study Termination ...................................................................................................................... 18 


 
 
 
 
 
 
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10.7. Study Medication Administration .............................................................................................. 18 
10.8. Concomitant Medications .......................................................................................................... 18 
11. 
STUDY ADMINISTRATION ....................................................................................................... 18 
11.1. Adherence to the Protocol ......................................................................................................... 18 
11.2. Amending the Protocol .............................................................................................................. 19 
11.3. Direct Access to Source Data/Documents ................................................................................. 19 
11.4. Quality Control and Quality Assurance ...................................................................................... 19 
11.5. Data Monitoring Committee (DMC) .......................................................................................... 19 
11.6. Ethical Considerations and Patient’s Consent ........................................................................... 19 
11.6.1. Ethical Considerations .................................................................................................. 19 
11.6.2. Institutional Review Board (IRB) ................................................................................... 19 
11.6.3. Written Informed Consent ........................................................................................... 19 
11.7. Data Handling and Recordkeeping............................................................................................. 20 
11.7.1. Patient Study File Completion ...................................................................................... 20 
11.7.2. Retention of Records .................................................................................................... 20 
11.8. Regulatory Documentation ........................................................................................................ 20 
11.9. Final Study Report ...................................................................................................................... 20 
11.10. Financing and Insurance ............................................................................................................ 20 
12. 
REFERENCES ........................................................................................................................... 21 
 
 
 
LIST OF TABLES 
Table 1: List of Abbreviations and Definitions of Terms ............................................................................... 6 
Table 2: Study Schedule ................................................................................................................................ 9 
 
 
 
 


 
 
 
 
 
 
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1. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 1: List of Abbreviations and Definitions of Terms 
Abbreviation/Term 
Definition 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BUN 
Blood Urea Nitrogen 
CO2 
Carbon Dioxide 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRP 
C-Reactive Protein 
CTCA 
Cancer Treatment Centers of America 
DCF 
Data Clarification Form 
DHA 
Docasahexaenoic Acid 
DMC 
Data Monitoring Committee 
EFA 
Essential Fatty Acid 
EPA 
Eicosapentaenoic Acid 
G 
gram 
GCP 
Good Clinical Practice 
GGT 
Gamma-Glutamyl Transferase 
Hbg 
Hemoglobin 
Hct 
Hematocrit 
Hr 
hour 
ICF 
Informed Consent Form 
ICU 
Intensive Care Unit  
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
Kg 
kilogram 
LDH 
Lactic Acid Dehydrogenase 
LOS 
Length of Stay 
MCH 
Mean  Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg/dL 
Milligram per deciliter 
mL 
Milliliter 
ml/kg 
Milliliters per kilogram 
MPV 
Mean Platelet Volume 
NCR 
No Carbon Required 
PN 
Parenteral Nutrition 
PT 
Prothrombin Time 
PTT 
Partial Thromboplastin Time 
RBC 
Red Blood Count 
RDW 
Red Cell Distribution Width 
SAE 
Serious Adverse Event 
TG 
Triglycerides 
TNF 
Tumor Necrosis Factor 
WBC 
White Blood Count 
WHODDE 
World Health Organization medical dictionary  
< 
Less than 
> 
Greater than 
= 
Equal to 
 
 
 


 
 
 
 
 
 
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2. 
INTRODUCTION 
2.1. Background 
Parenteral nutrition (PN), when required for long-term nutrition support, may lead to hepatic 
dysfunction (ADA pocket guide to PN).  PN can be the cause of hyperbilirubinemia and elevated liver 
function tests.  Patients at increased risk of developing hepatic dysfunction from PN are those with 
primary gastrointestinal disorder, pre-existing liver disease, malnutrition, or sepsis (ref).  The cause of 
this dysfunction may be related to the provision of excess calories, excess individual macronutrients, 
and deficiencies of choline, L-carnitine, and/or glutamine.  This dysfunction can progress to liver failure 
in patients requiring long-term PN. 
 
There are recommendations to try to prevent PN induced hepatic dysfunction.  They include but are not 
limited to avoiding excess calorie, carbohydrate, and/or lipid infusion; limiting infusion time; some oral 
or enteral nutrients if possible; and possibly adding choline, L-carnitine, and/or glutamine to the PN.  
Despite following these recommendations, patients may still develop PN induced hepatic dysfunction.  
This may result in the need to discontinue PN. 
 
Patients with advanced cancer requiring PN for long-term nutrition support may be at increased risk for 
developing this condition due to gastrointestinal failure, liver metastases, and malnutrition.  If these 
individuals begin to experience elevation of bilirubin and/or liver function tests, the calories from 
macronutrients may have to be reduced, resulting in underfeeding in those that may already be 
malnourished.  If after reducing calories from macronutrients and adding L-carnitine to the PN, liver 
function does not improve, the PN may have to be held or discontinued.  This results in severe under 
nutrition or in some cases no source of nutrition. 
 
Lipid emulsions are added to parenteral nutrition to provide calories and essential fatty acids.  Currently, 
the lipid emulsions used in the United States (U.S.) are long chain triglycerides from soybean or 
safflower oil, which have a high ratio of n-6 to n-3 polyunsaturated fatty acids (Wanten 2007).  There is 
some evidence to suggest that the n-6 lipid emulsions used in PN may be associated with PN induced 
steatohepatitis and an increase in pro-inflammatory eicosanoids resulting in immune suppression 
(Wanten 2007, Kinsella 1990).  Omega-3 fatty acid containing lipid emulsions are not available in the 
U.S., but they are available and are being studied in Europe and Taiwan.  Omega-3 fatty acid containing 
lipid emulsions have been shown to prevent or attenuate PN-induced hepatosteatosis in normal rats 
and mice (Chen 1996, Alwayn 2005).  In addition, these solutions have been shown to ameloriate diet-
induced hepatosteatosis in rats (Yeh 1996).  Most recently, in a non-randomized study using historical 
controls, 18 infants with short-bowel syndrome who developed cholestasis, were given a fish-oil based 
fat emulsion.  Reversal of cholestasis was achieved 4.8 times faster (9.4 weeks vs. 44.1 weeks) in those 
receiving the fish oil emulsion compared to historical controls that received soybean emulsions.  Also, 
the fish-oil based emulsion was safe and was not associated with essential fatty acid deficiency, 
hypertriglyceridemia, coagulopathy, or infection (Biank 2008).   
 
In addition to the potential role omega-3 lipid emulsions may play in reversing PN induced hepatic 
injury, they may help decrease the inflammatory response and have a beneficial effect on clinical 
outcomes.  Morlion et al. (1996) found that 5-days of a parenteral fish oil supplement resulted in a 
change in leukotriene synthesis to a more favorable 5 series and a decreased length of stay in surgical 
patients.  Pluess et al. (2007) demonstrated that a two day infusion of a fish-oil emulsion (Omegaven) in 
healthy volunteers given an endotoxin increased eicosapentaenoic acid (EPA) and docasahexaenoic acid 


 
 
 
 
 
 
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(DHA) content in platelet phospholipids and decreased tumor necrosis factor alpha compared to 
controls.   
 
Other studies have found a decrease in intensive care unit (ICU) days and length of stay with fish-oil 
emulsions.  Heller et al. (2006) in a prospective, open label, multiple-center trial found that 
administration of a fish-oil emulsion reduced mortality, antibiotic use, and length of stay in different 
diseases.  A total of 661 patients receiving PN for ≥ 3 days were included in the study to evaluate dose-
dependent effects of fish-oil emulsion.  The mean dose given was 0.11 g/kg/day.  The most favorable 
effects on survival, infections, and length of stay were at doses of 0.1 and 0.2 g/kg/day.  Antibiotic use 
was lowered by 26% with doses of 0.15-0.2 g/kg/day.  Finally, a dose of 0.23 g/kg/day was associated 
with a decrease in ICU LOS.  No bleeding or other adverse events were reported. 
 
Heller et al. (2004) also found that fish oil supplemented PN improved liver and pancreas function in a 
prospective, randomized, double-blind clinical trial on 44 patients having major abdominal cancer 
surgery. Patients were randomized to receive either PN with soybean oil or a combination of soybean 
and fish oil for 5 days.  The fish oil group had reduced AST, ALT, & bilirubin after surgery.  The fish oil 
group also trended towards having a shorter ICU stay.  Also, the soybean only group lost 1.1±2.2 kg, 
while the fish oil group did not lose weight. 
 
In a prospective, double-blind, randomized, controlled study of 42 patients requiring radical resection 
for colon cancer, Liang et al. (2008) found a favorable effect on the inflammatory and immune response 
with the use of an omega-3 lipid emulsion postoperatively.  All patients received PN for 7 days 
postoperative.  The control group received standard omega-6 lipid emulsion while the study group had 
some of the omega-6 lipid in their PN replaced with omega-3.  On post-op day 8, serum IL-6 levels were 
significantly lower with omega-3.  Also, with omega-3, the ratio of CD4+/CD8+ was significantly 
increased; TNF-α was decreased; and CD4+ lymphocyte percentage was increased. 
2.2. Risk Category 
(45 CFR 46.405) Category 2: Research involving greater than minimal risk, but presenting the prospect of 
direct benefit to the individual patients. 
2.3. Rationale 
Omegaven may be effective in stabilizing or reversing hepatic injury associated with the use of PN.  In 
addition, omega-3 lipid emulsions may help decrease the inflammatory response and have a beneficial 
effect on clinical outcomes.   This compassionate use protocol provides a mechanism for physicians to 
better understand the efficacy of Omegaven for the treatment of patients with advanced cancer 
requiring PN for long-term nutrition support who have developed PN-induced hepatic injury or who 
have existing hepatic dysfunction. 
2.4. Statement 
This study will be conducted in compliance with the protocol, the guidelines of Good Clinical Practices 
(GCP), the current revision of the Declaration of Helsinki, and the applicable regulatory requirements. 
3. 
OBJECTIVES 
The primary objective for this study is to examine if an omega-3 based lipid emulsion (Omegaven) can 
improve or prevent further deterioration of PN induced hepatic dysfunction. 


 
 
 
 
 
 
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The secondary objective for this study is to examine the effect of an omega-3 based lipid emulsion 
(Omegaven) on immune function and markers of the inflammatory process. 
4. 
INVESTIGATIONAL PLAN 
4.1. Study Design 
This compassionate use study will include patients with advanced cancer requiring PN for long-term 
nutrition support who have developed PN-induced hepatic injury or who have existing hepatic 
dysfunction.  Therapy with Omegaven will be provided at an initial dose of 0.1 g/kg body weight 
(1ml/kg) and increased to 0.2 g/kg body weight (2ml/kg) on day 2 or 3 of treatment.  For patients > 
120% ideal body weight, adjusted body weight will be used.   The infusion rate will not exceed 0.5mL 
Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). Omegaven will be co-administered 
via a y-site infusion, with containers being changed every 12 hours.   The patient may receive other lipids 
to meet Essential Fatty Acid (EFA) and/or additional calorie needs.  Patients will receive the initial 
infusion of PN containing Omegaven at Midwestern Regional Medical Center (MRMC) in the infusion 
center to observe for adverse reactions. If an adverse reaction is observed, IV steroids & benadryl will be 
administered & Omegaven will be discontinued.  Patients will continue to receive infusions at CTCA for 
the first 2 to 3 days of dosing.  After tolerance is established, patients will receive treatment at home 
with Coram. All study patients will have a Screening Visit; Day 1, Day 2 and Day 3 visits; and weekly visits 
for one month (see Table 2).  
 
Table 2: Study Schedule 
Visit: Screening 
Day 1 
Day 2  
Day 3 
Weekly 
Visits  
Final Study Visit/ 
Early Withdrawal 
Informed Consent Form 
X 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
Physical Exam 
X 
 
 
 
 
X 
Vital Signs  
X 
X 
X 
X 
X 
X 
Medical History 
X 
 
 
 
 
 
Blood hematology/chemistry  
X 
X 
X 
X 
X 
X 
Triglyceride level monitoring1 
 
X 
X 
X 
X 
 
Dispense study medication 
 
X 
X 
X 
X 
 
Infusion given at MRMC2 
 
X 
X 
 
 
 
Infusion given at MRMC or at 
the patient’s home 
 
 
 
X 
X 
 
Adverse Events (AEs) 
 
X 
X 
X 
X 
X 
Concomitant medications 
 
X 
X 
X 
X 
X 
Education on home PN & 
Omegaven 
 
X 
 
 
 
 
Assess patient compliance 
 
 
 
X 
X 
 
Clinical supplies accounted for 
& destroyed 
 
 
 
 
 
X 
 
                                                     
1 Triglyceride level monitoring will occur daily from the time the patient begins Omegaven dosing until Omegaven dosing is 
complete. 
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4.2. Study Procedures by Visit 
4.2.1. 
Screening Visit 
Cancer patients with hepatic injury will be offered Omegaven for compassionate use situations when 
there are no satisfactory alternative treatments.  Patients meeting the criteria for this study will be 
screened for participation at the MRMC.  The following will occur for all patients at the Screening Visit: 
• 
Prior to performing any study procedures, the patient will be informed about the trial and asked 
to sign and date the Informed Consent Form (ICF). The person who conducted the informed 
consent discussion will also be required to sign and date the ICF. 
• 
Patient eligibility will be assessed based on the inclusion and exclusion criteria (Sections 5.1 and 
5.2). 
• 
A complete physical examination with vital signs and medical history and historical medications 
will be done. 
• 
Blood will be drawn for hematology and chemistry lab panels (see Section 4.3.1).  
4.2.2. 
Day 1 Visit 
The Day 1 Visit and the Screening Visit can occur on the same day.    The Day 1 Visit will occur at CTCA, 
and the following will occur at this visit: 
• 
Blood will be drawn for hematology and chemistry lab panels (see Section 4.3.1).   
• 
Any medication changes and/or medications taken since the Screening Visit will be recorded. 
• 
Education will be provided by site personnel on Omegaven and on home PN for those patients 
who will be receiving infusions in their homes. 
Patients will be treated with an initial dose of Omegaven at 0.1 g/kg body weight (1ml/kg) by continuous 
infusion at CTCA.  The infusion rate will not exceed 0.5mL Omegaven/kg body weight/hr (corresponding 
to 0.05g fish oil/kg/hr). Triglycerides (TGs) will be monitored daily and a dose reduction will occur if: 
o TG levels rise above 400 mg/dL, 
o If evidence of bleeding occurs. 
• Any changes to the patient’s health (Adverse Events/AEs) from the time infusion begins will be 
recorded. 
4.2.3. 
Day 2 Visit 
The Day 2/Day 3 Visit will occur at CTCA.  At this visit, the following will occur for all patients: 
• 
Vital signs will be taken. 
• 
Blood will be drawn for hematology and chemistry lab panels  (see Section 4.3.1).   
• 
Omegaven dosing will occur via continuous infusion at CTCA. The infusion rate will not exceed 
0.5mL Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). 
• 
The Omegaven dose will be increased to 0.2 g/kg body weight (2 ml/kg).   
• 
AEs and Concomitant Medications since the previous visit will be recorded. 
4.2.4. 
Day 3 Visit 
The Day 3 Visit may occur at the patient’s home.  At the Day 3 Visit, the following will occur for all 
patients: 
• 
Vital signs will be taken. 
• 
Blood will be drawn for hematology and chemistry lab panels (see Section 4.3.1).   
• 
Omegaven dosing will occur via continuous infusion at either CTCA or in the patient’s home. The 
Omegaven dose will remain at 0.2 g/kg body weight (2 ml/kg).  The infusion rate will not exceed 
0.5mL Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). 


 
 
 
 
 
 
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• 
AEs and Concomitant Medications since the previous visit will be recorded. 
• 
Drug accountability will be performed by the homecare nurse to assess patient compliance if the 
patient has received doses in the home without a nurse present. 
4.2.5. 
Weekly Visits During Home Use of Omegaven (up to 4 weeks of treatment) 
Patients will be monitored by healthcare nurses during home health visits every week until withdrawal 
from the study. The first weekly visit will occur 7 ±1 days after the first dose, and continue every 7 ± 1 
days thereafter.  During these home health visits the following will occur: 
• 
Vital signs will be taken. 
• 
Blood will be drawn for hematology and chemistry lab panels (see Section 4.3.1).   
• 
Omegaven dosing will occur via continuous infusion at either CTCA or in the patient’s home. The 
Omegaven dose will remain at 0.2 g/kg body weight (2 ml/kg).  The infusion rate will not exceed 
0.5mL Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). 
• 
AEs and Concomitant Medications since the previous visit will be recorded. 
• 
Drug accountability will be performed by the homecare nurse to assess patient compliance if the 
patient has received doses in the home without a nurse present.  
 
Omegaven will be given for: 
• 
4 weeks, or  
• 
Until serum bilirubin is < 2 mg/dL, or  
• 
Until normalization in liver function tests. 
4.2.6. 
Final Study Visit/Early Withdrawal Visit 
At the patient’s Final Study Visit/Early Withdrawal Visit, the following will occur: 
• 
A physical exam will be performed. 
• 
Vital signs will be taken. 
• 
Blood will be drawn for hematology and chemistry lab panels and additional toxicity labs (see 
Section 4.3.1).   
• 
AEs and Concomitant Medications since the previous visit will be recorded. 
• 
Drug accountability will be performed by the homecare nurse to assess patient compliance if the 
patient has received doses in the home without a nurse present. 
• 
Any remaining clinical supplies will be accounted for and destroyed. 
4.3. Description of Study-Specific Procedures 
4.3.1. 
Diagnostic Tests 
The following diagnostic laboratory tests will be performed: 
• 
Blood Hematology and Chemistry 
o Hematology:  white blood cell count (WBC or leukocyte count), WBC differential count, red 
blood cell count (RBC or erythrocyte count), hematocrit (Hct), hemoglobin (Hbg), mean 
corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular 
hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count, and 
mean platelet volume (MPV) 


 
 
 
 
 
 
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o Chemistry: Blood Urea Nitrogen (BUN), carbon dioxide (CO2), creatinine, glucose, serum 
chloride, serum potassium, serum sodium, serum calcium, serum phosphorus, serum 
magnesium, triglycerides and a liver panel: alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), 
albumin, total protein, direct bilirubin (conjugated), total bilirubin 
o Additional  Labs: An additional clot tube of blood will be collected and stored at baseline and 
at the end of 4 weeks or withdrawal from study to evaluate treatment response. 
 
The investigator, or a qualified designee who is part of the study team, will promptly review each lab 
report as it becomes available. If the investigator deems a value outside the reference range to be 
“clinically significant,” then she/he will record it as an adverse event (AE).  Lab reports will become a 
part of the source documentation.  
5. 
SELECTION AND WITHDRAWAL OF PATIENTS 
5.1. Patient Inclusion Criteria 
A patient must meet the following criteria to be included in this study: 
I.1 
Male of Female; ages 18 to 80 
I.2 
Receiving treatment at CTCA 
I.3 
Receiving PN (either in the infusion center or at home) 
I.4     Have existing hepatic dysfunction defined as Elevation of >3x the normal level of one or more 
          of the following:  Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), or Alanine  
          Aminotransferase (ALT) and/or Bilirubin > 2 mg/dl in the absence of biliary obstruction. 
I.5      Able to provide informed written consent (patient or legally acceptable representative) 
5.2. Patient Exclusion Criteria 
A patient will be excluded from the study for any of the following reasons:  
E.1 
Hypertriglyceridemia (fasting triglycerides [TG] > 400) 
E.2 
Allergy to fish or egg protein 
E.3 
Currently on therapeutic doses of Coumadin, heparin, or low molecular weight heparin. 
E.4 
Hemodynamically unstable 
E.5 
Bilirubin > 5 mg/dL 
E.6 
Documented progression of liver metastases 
E.7 
Unstable diabetes with known diabetic ketoacidosis within 7 days of screening 
E.8 
Recent cardiac infarction taking plavix 
E.9 
Severe hemorrhagic disorders 
E.10 Embolism 
E.11 Sepsis 
E.12 Undefined coma status 
E.13 Renal insufficiency defined as creatinine clearance < 30 mL/min. 
E.14 Pregnancy or lactation 
5.3. Patient Withdrawal Criteria 
Patients may be terminated from the study for the following events and reasons: 
W.1 The patient chooses to withdraw for any reason  
W.2 The Investigator chooses to terminate the patient from the study.  Reasons could include: 


 
 
 
 
 
 
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a. Occurrence of AEs related to the use of Omegaven; adverse reaction to Omegaven 
b. Patient non-compliance  
c. Patient discovered after enrollment not to have met the protocol entrance criteria 
W.3 Therapy goals are reached: patient able to meet and sustain nutrient needs by oral nutrition 
W.4 Patient lost to follow-up 
W.5 The principal-investigator terminates the study 
W.6  If bilirubin elevates to > 5 mg/dl due to obstruction 
 
W.7 Requires open surgical procedure 
W.8 Documented progression of liver metastases contributing to worsening of hepatic 
dysfunction. 
 
If a patient does not return for a scheduled visit every effort should be made to contact the patient. In 
any circumstance, every effort should be made to document patient outcome, if possible. Patients will 
only be considered lost to follow-up if study personnel are unable to communicate with the patient or 
the patient‘s legally acceptable representative by three telephone attempts and certified letter.  
Reasons for withdrawal will be specified in the patient’s study file, and will include date of 
discontinuation of investigational product and date of study withdrawal.  
6. 
CONCOMITANT MEDICATIONS/TREATMENT 
The patient will be queried regarding concomitant use of medications at all study visits. All concomitant 
medication use (both prescription and over-the-counter, including herbal medications and nutritional 
supplements) will be reported during the study, and recorded in the patient’s study file. 
 
Patient will be instructed to avoid any oral supplements containing omega-3 fatty acid supplements 
during this protocol. 
 
The patient may receive other lipids to meet essential fatty acid (EFA) and/or additional calorie needs. 
7. 
COMPLIANCE 
Treatment compliance can be assessed using drug accountability records. The home healthcare nurse 
will collect any used/unused bottles at each visit and maintain a patient accountability record of all 
study medication that is distributed, administered, and collected for destruction. 
8. 
INVESTIGATIONAL MATERIALS AND MANAGEMENT 
8.1. Investigational Product 
8.1.1. 
General Investigational Product Information 
Bottles containing 50 mL or 100 mL of 10% Omegaven will be purchased from International Pharmacy of 
Hamburg, Germany. Omegaven is manufactured by Fresenius Kabi AG, Bad Homburg v.d.h, Germany. 
Omegaven is formulated as an emulsion from fish oils. 


 
 
 
 
 
 
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8.1.2. 
Dosing 
Patients will be treated with Omegaven on day 1 at a dose of 0.1 g/kg body weight (1 ml/kg).  On day 2 
or 3, it will be increased to 0.2 g/kg body weight (2 ml/kg).  For patients > 120% ideal body weight, 
adjusted body weight will be used for dosing.  The infusion rate will not exceed 0.5 ml Omegaven/kg 
body weight/hr = 0.05 g fish oil/kg body weight/hr.    
 
Omegaven will be co-infused via a y-site.  Containers will be changed every 12 hours.  Omegaven will be 
given through a 1.2 micron inline filter. 
 
Omegaven will be given for: 
• 
4 weeks, or  
• 
Until serum bilirubin is < 2 mg/dL, or  
• 
Until normalization of liver function tests. 
8.1.3. 
Dispensation  
Omegaven will be dispensed by the CTCA pharmacy and homecare pharmacies per the applicable 
policies and procedures for fat emulsions. 
8.1.4. 
Storage and Handling  
Omegaven bottles will be stored at room temperature at ≤ 25° C (do not freeze). Damaged or suspect 
drug will be returned unused to Fresenius-Kabi. Containers should be shaken before use. 
8.1.5. 
Accountability  
All supplies for the study will be accompanied by accountability and shipping documents and will be 
maintained by the CTCA pharmacy and/or the homecare pharmacy. 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 study, all 
used and unused Omegaven will be accounted for.  If expired, the remaining drug supplies will be 
destroyed.  
8.1.6. 
Dose Adjustments  
A dose reduction will occur if: 
• 
TG levels rise above 400 mg/dL, 
• 
If evidence of bleeding occurs. 
9. 
ASSESSMENT OF EFFICACY AND SAFETY 
9.1. Outcome Variables 
Efficacy and safety will be assessed using the following outcome variables: 
• 
Laboratory results  
• 
AEs reported by the patient and/or identified by study personnel 
• 
Resolution of hepatic injury 
9.2. Adverse Event (AE) Recording/Reporting 
An AE is any untoward medical occurrence in a patient or clinical investigation patient participating in a 
clinical study and which does not necessarily have to have a causal relationship with this treatment or 


 
 
 
 
 
 
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clinical study. An AE can therefore be any unfavorable and unintended sign (including abnormal 
laboratory findings, for example), symptom, or disease temporally associated with the use of the 
medicinal product, whether or not considered related to the medicinal product. 
 
AEs include illnesses, signs, or symptoms, independent of causality, that appear or worsen during the 
course of the study. Whenever the investigator is confident of the diagnosis, he/she should group 
together as a single illness all related signs, symptoms, and abnormal laboratory test results (e.g., cough, 
rhinitis, and sneezing should ordinarily be reported as “upper respiratory tract infection”). 
 
An investigator will promptly review each lab report. Laboratory AEs are defined as clinical laboratory 
results that are outside of the normal ranges and are deemed clinically significant by the investigator. 
Clinically significant laboratory results will be recorded as AEs. Laboratory reports will become a part of 
the patient’s study file. 
 
Procedures, such as surgery, should not be reported as AEs or Serious Adverse Events (SAEs). However, 
the medical condition for which the procedure was performed should be reported if it meets the AE/SAE 
definition. For example, an acute appendicitis that begins during the AE reporting period should be 
reported as the AE and the resulting appendectomy noted in comments. In addition, an elective surgery 
(and any related hospitalization) whether or not there is an existing medical condition should not be 
reported as an AE. 
 
The AE reporting period for this study begins at the time the first Omegaven infusion is administered 
and ends at the final study visit. Any abnormal physical examination findings identified during screening 
will generally be considered part of the medical history and not an AE. A preexisting condition (i.e., a 
disorder present before the AE reporting period started and noted on the medical history/physical) 
should not be reported as an AE unless the condition worsens or episodes increase in frequency during 
the AE reporting period. 
 
All AEs will be recorded in each patient’s study file. The following definitions will be applied to AE 
reports: 
Severity 
MILD 
Awareness of signs or symptoms, but they are easily tolerated 
MODERATE 
Enough discomfort to cause interference with usual activity 
SEVERE 
Incapacitating, with inability to work or do usual activity 
 
Action Taken 
NONE 
TREATMENT OTHER THAN MEDICATIONS REQUIRED 
MEDICATIONS REQUIRED 
DISCONTINUED  
(Study medication permanently stopped) 
 
Relationship to Study Medication 
NONE 
Causal relationship can be ruled out 
POSSIBLY 
Causal relationship at least reasonably possible, i.e., relationship can’t be ruled out 
DEFINITELY 
Causal relationship is certain 
 


 
 
 
 
 
 
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Patients experiencing AEs that result in study drug discontinuation or those experiencing AEs that are 
present at the end of their participation in the study will receive follow-up until the AE is resolved, 
attributed to a cause other than study medication administration, or assessed as chronic or stable. 
9.3. Serious Adverse Event (SAE) Recording/Reporting 
An SAE for this study is one that meets any one of the following criteria: 
• 
Fatal or life-threatening 
• 
Requires or prolongs in-patient hospitalization 
• 
Results in persistent or significant disability/incapacity  
• 
Important medical event 
 
Medical and scientific judgment should be exercised in deciding whether an important medical event is 
serious. Although the event may not be immediately life threatening, fatal, or result in hospitalization, it 
should be considered serious when it jeopardizes the patient, or requires an intervention to prevent a 
serious outcome as defined above. Examples of serious medically important events are: intensive 
treatment in an emergency room or at home for allergic bronchospasm; blood dyscrasia or convulsion 
that do not result in hospitalization. 
 
The term “life threatening” in the definition of “serious” refers to an event in which the patient was at 
risk of death at the time of the event; it does not refer to an event that hypothetically might have 
caused death if it were more severe. The term “in-patient hospitalization” in the definition of “serious” 
refers to an event in which the patient was admitted to the hospital for one or more days, even if 
release on the same day; or an emergency room visit, which results in admission to the hospital. 
Emergency room visits that do not result in admission to the hospital should be evaluated for one of the 
other serious outcomes criteria (e.g., important medical event). 
 
The SAE reporting period begins at the time the first Omegaven infusion is administered and ends at the 
last study visit. SAEs that are considered at least possibly related to the study medication or that occur in 
a pregnancy that began while the patient was using the study medication can be reported at any time. 
 
All SAEs will be followed through resolution or until the investigator attributes the SAEs to a cause other 
than the study medication or assesses them as chronic or stable. Follow-up SAE reports should adhere 
to the same procedures and timelines as initial reports. In addition, any SAE that occurs subsequent to 
the reporting period that the investigator assesses as possibly related to the study medication should 
also be considered for follow-up. 
9.4. IND Safety Reporting 
The Principal-Investigator for this IND shall promptly review all information relevant to the safety of the 
drug obtained or otherwise received from any source, foreign or domestic, including information 
derived from any clinical or epidemiological investigations, animal investigations, commercial marketing 
experience, reports in the scientific literature, and unpublished scientific papers, as well as reports from 
foreign regulatory authorities that have not already been previously reported to the agency by the 
Principal-Investigator.  The Principal-Investigator of a clinical study of a marketed drug is not required to 
make a safety report for any AE associated with use of the drug that is not from the clinical study itself. 


 
 
 
 
 
 
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9.4.1. 
Written IND Safety Report 
The Principal-Investigator shall notify FDA and all participating investigators in a written IND safety 
report of: 
• 
Any AE associated with the use of the drug that is both serious and unexpected; or 
• 
Any finding from tests in laboratory animals that suggests a significant risk for human subjects 
including reports of mutagenicity, teratogenicity, or carcinogenicity.  
Each notification shall be made as soon as possible and in no event later than 15 calendar days after the 
Principal-Investigator's initial receipt of the information. Each written notification may be submitted on 
FDA Form 3500A or in a narrative format.   In each written IND safety report, the Principal-Investigator 
shall identify all safety reports previously filed with the IND concerning a similar AE, and shall analyze 
the significance of the AE in light of the previous, similar reports. 
 
Follow-up information to an IND Safety Report shall be submitted as soon as the relevant information is 
available.  If the results of the Principal-Investigator’s follow-up investigation show that an AE that was 
initially determined to not require a written IND Safety Report does, in fact, meet the requirements for 
reporting; Principal-Investigator will submit a written IND Safety Report as soon as possible, but in no 
event later than 15 calendar days, after the determination was made.  Additional safety information 
shall be submitted, as appropriate, in an information amendment or annual report. 
9.4.2. 
Telephone or Fax IND Safety Reports 
The sponsor shall also notify FDA by telephone or by fax of any unexpected fatal or life-threatening 
experience associated with the use of the drug as soon as possible but in no event later than 7 calendar 
days after the Principal-Investigator's initial receipt of the information.   
9.5. IRB Safety Reporting 
Adverse event submissions to the Institutional Review Board (IRB) responsible for this study will follow 
the responsible IRB’s requirements.  
10. 
DATA MANAGEMENT  
10.1. Data Management 
All patient study files will be centralized with the Principal-Investigator. 
10.2. Sample Size Determination 
This is a compassionate use study that is expected to enroll 30 patients.   
10.3. Disposition and Baseline Assessment 
In the event that a patient withdraws prematurely from the study, the reasons for withdrawal will be 
documented in the patient’s study file. Patients who discontinue study medication or withdraw 
prematurely from the study will be summarized, together with the reason(s) for discontinuation.   
10.4. Outcomes Analysis 
This is a compassionate use study, with no comparator; therefore the endpoints will be descriptively 
summarized (continuous data will be presented as mean, standard deviation, median, minimum and 
maximum; categorical data will be presented as number and percentage).  All patients who receive any 
amount of study medication will be analyzed.  The outcome evaluations will include: 


 
 
 
 
 
 
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• 
Laboratory results – Laboratory values will be summarized at baseline and as change from 
baseline to worst follow-up values.   
• 
AEs reported by the patient and/or identified by study personnel – AEs may be categorized 
into common terms and summarized as incidence and event rates.  If there is sufficient data the 
incidence rates may also be summarized by AE severity and relationship to study medication.   
• 
Resolution of hepatic injury – Resolution of hepatic injury will be summarized as incidence and 
if there is sufficient data may also be presented as time to resolution. 
• 
Days of PN – Days of PN will be summarized. 
10.5. Data Monitoring Committee 
No plans for a Data Monitoring Committee (DMC).   
10.6. Study Termination 
This is a compassionate use study, intended to make a study medication available to patients who would 
otherwise not be able to receive this medication, therefore there is no predefined completion of this 
study.  When the study is terminated for any reason, the patients will be treated as deemed appropriate 
by their usual healthcare provider. Some of the possible reasons for study termination are patient 
safety, Principal-Investigator termination of the study, etc.  
 
Safety will be monitored throughout the study and if a safety concern indicative of a risk for the 
individual patients or the study population is identified at any time during the study, this will warrant 
further review and may result in the termination of the study.  
10.7. Study Medication Administration 
Study medication administration will be summarized. Any deviation from the planned dosing schedule 
will be documented and summarized. 
10.8. Concomitant Medications 
Concomitant medications are the medications that are taken during the study. Information on the 
concomitant medications will be collected in the patient’s study file.  
11. 
STUDY ADMINISTRATION 
11.1. Adherence to the Protocol 
Except for changes that are intended to eliminate an immediate hazard to patients, the approved 
protocol shall be conducted as described. Any protocol deviation or violation must be documented. Any 
protocol-related issue that poses an immediate or significant hazard to patients must be reported to the 
IRB immediately. 
 
The Principal-Investigator may not implement any deviation or change to the protocol without prior 
review/favorable opinion of the appropriate regulatory authorities (e.g., IRB), except where necessary to 
eliminate an immediate hazard to a patient or when the change involves only a logistical or 
administrative aspect of the study (e.g., change of telephone numbers, ancillary personnel). Any 
deviation from the protocol must be documented and explained in written communication to the 
appropriate regulatory authorities. 
 


 
 
 
 
 
 
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This clinical study will be conducted in compliance with the protocol, Good Clinical Practices (GCPs), and 
the applicable regulatory requirements. Where applicable, the protocol designates study responsibilities 
to the “Investigator”. Those tasks may be performed by the Principal Investigator or qualified designee. 
11.2. Amending the Protocol 
Any change to the protocol, once the final version has been issued, has to be detailed in a protocol 
amendment. All protocol modifications and amendments must be prepared for and approved by the 
IRB.  All amendments must be numbered, dated and signed. Amendments cannot be implemented until 
final approval from the IRB. 
11.3. Direct Access to Source Data/Documents 
All representatives of the Principal-Investigator with direct access to patients’ medical records will take 
reasonable precautions within the constraints of applicable regulatory requirements to maintain the 
confidentiality of the patients’ identity.  Auditors of the IRB and government inspectors may evaluate 
the study and must be allowed access to the patient study files, source documents and other study files. 
Audit reports will be kept confidential.  
11.4. Quality Control and Quality Assurance 
Quality assurance measurements are designed to ensure that complete, timely and accurate data are 
submitted, that protocol requirements are followed, and that complications and/or AEs are immediately 
identified. Quality assurance audits may be carried out during the conduct of the study. Quality 
assurance personnel independent of personnel conducting the study will carry out these audits. The 
quality assurance auditor should have access to all medical records, the Principal-Investigator's study-
related files and correspondence, and the informed consent documentation that is relevant to this 
clinical study. 
11.5. Data Monitoring Committee (DMC) 
No plans for a DMC. 
11.6. Ethical Considerations and Patient’s Consent 
11.6.1. Ethical Considerations 
The study will be carried out in accordance with the principles stated in the Declaration of Helsinki and 
in accordance with Good Clinical Practice (GCP) and applicable regulatory requirements. 
11.6.2. Institutional Review Board (IRB) 
According to the applicable regulatory requirements, the investigator will submit the study 
documentation to the relevant IRBs. The letter of approval from the IRB (or a copy), which contains a list 
of the names and occupations of the members of the IRB having participated at the session, as well as a 
list of submitted documents, must be received by the Principal-Investigator prior to study medication 
being received at the study site. Patients must not be entered into the study until approval of the IRB(s) 
as defined by local regulatory requirements. All subsequent substantial amendments must be submitted 
to the IRB(s) for approval/information. 
11.6.3. Written Informed Consent 
A patient may be included in this study only after an IRB-approved Informed Consent Form (ICF) has 
been signed and dated by the patient.  The patient must be informed about the content of the planned 


 
 
 
 
 
 
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study as well as on the benefit/risk ratio. The person who conducts the informed consent discussion at 
the study site will also be required to sign and date the ICF. 
11.7. Data Handling and Recordkeeping 
11.7.1. Patient Study File Completion 
All patient study files will be filled out in permanent ink or typed. Corrections of data on the patient 
study files will be made only by crossing out the incorrect data and writing the correct values next to 
those crossed out. Each correction will be initialed and dated by the person making the correction. If 
corrections are made after review and signature by the Investigator, the Investigator will be made aware 
of the changes and his/her awareness will be documented by initialing and dating the changes. 
11.7.2. Retention of Records 
The site shall retain study medication disposition records, patient study files, and source documents for 
all patients enrolled for the period required by applicable regulatory requirements, the Institution in 
which the study will be conducted, or for a minimum of two years after shipment and delivery of the 
study medication is discontinued. The site should take measures to prevent accidental or premature 
destruction of the study documents for as long as they have to be maintained.  
11.8. Regulatory Documentation 
Documentation responsibilities of the site before or during the study include the following: 
• 
Maintain accreditation or certification number and a list of reference ranges from any local 
laboratory that will be used (if applicable).  
• 
Maintain appropriate regulatory forms along with a current copy of a curriculum vitae and 
medical license for each investigator in the study. 
• 
Maintain a list of all persons whose participation materially affects the study (ancillary 
personnel). Must also include their training and/or title and the role they will assume in the 
study.  If any changes to study personnel are made during the study, the log outlining the 
delegation of authority will be updated.  
11.9. Final Study Report 
A final study report will be prepared by the investigator according to applicable regulatory guidance.  
11.10. Financing and Insurance 
The study is fully financed by the Sponsor (Coram) and is insured.  
 
 


 
 
 
 
 
 
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12. 
REFERENCES 
Alwayn IP, Gura K, Nosé 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. 
Biank VF. Safety and Efficacy of a Fish-Oil-Based Fat Emulsion in the Treatment of Parenteral Nutrition-Associated 
Liver Disease. Nutrition in Clinical Practice. 2008 Aug ;23(4):445-446. 
Chen WJ, Yeh SL, Huang PC. Effects of fat emulsions with different fatty acid composition on plasma and hepatic 
lipids in rats receiving total parenteral nutrition. Clin Nutr. 1996 Feb;15(1):24-8. 
Heller AR, Rössler S, Litz RJ, Stehr SN, Heller SC, Koch R, Koch T. Omega-3 fatty acids improve the diagnosis-related 
clinical outcome. Crit Care Med. 2006 Apr;34(4):972-9. 
Heller AR, Rössel T, Gottschlich B, Tiebel O, Menschikowski M, Litz RJ, Zimmermann T, Koch T. Omega-3 fatty acids 
improve liver and pancreas function in postoperative cancer patients. Int J Cancer. 2004 Sep 10;111(4):611-6. 
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 Jan-Feb;6(1):24-44; discussion 
59-62. 
Liang B, Wang S, Ye YJ, Yang XD, Wang YL, Qu J, Xie QW, Yin MJ. Impact of postoperative omega-3 fatty acid-
supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients. 
World J Gastroenterol. 2008 Apr 21;14(15):2434-9. 
Morlion BJ, Torwesten E, Lessire H, Sturm G, Peskar BM, Fürst P, Puchstein C. The effect of parenteral fish oil on 
leukocyte membrane fatty acid composition and leukotriene-synthesizing capacity in patients with postoperative 
trauma. Metabolism. 1996 Oct;45(10):1208-13. 
Pluess TT, Hayoz D, Berger MM, Tappy L, Revelly JP, Michaeli B, Carpentier YA, Chioléro RL. Intravenous fish oil 
blunts the physiological response to endotoxin in healthy subjects. Intensive Care Med. 2007 May;33(5):789-97. 
Epub 2007 Mar 22. Erratum in: Intensive Care Med. 2007 Jul;33(7):1310. 
Wanten GJ, Calder PC. Immune modulation by parenteral lipid emulsions. Am J Clin Nutr. 2007 May;85(5):1171-84.  
 
Yeh SL, Chen WJ, Huang PC. Effects of fish oil and safflower oil emulsions on diet-induced hepatic steatosis in rats 
receiving total parenteral nutrition. Clin Nutr. 1996 Apr;15(2):80-3.