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Study Comparing a Soybean Oil-Based With an Olive Oil-Based Lipid Emulsion in ICU Patients Requiring TPN (TPN2)

Primary Purpose

Parenteral Nutrition

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ClinOleic 20% Intravenous Emulsion
Intralipid, 20% Intravenous Emulsion
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parenteral Nutrition focused on measuring parenteral nutrition, lipid emulsion, nosocomial infection, mortality, endothelial function, inflammatory markers, oxidative stress, immune function, autonomic nervous system, insulin sensitivity, carbohydrate metabolism

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • Age: 18 - 80 years when initiating PN
  • In medical/surgical ICU
  • Has central venous access to administer PN
  • Anticipated to receive PN ≥ 5 days

Exclusion criteria:

  • Enrolled in an investigative study within the last 30 days prior to study entry
  • Female patients: pregnant or breast feeding
  • Has clinical sepsis (defined as mean arterial pressure (MAP) < 60 mmHg on ≥ 2 occasions and unstable BP despite pressor support) within 24 hours prior to study entry
  • Has known cirrhosis or total bilirubin ≥ 10.0 mg/dL
  • Has chronic renal failure (defined as requirement for hemodialysis or peritoneal dialysis therapy), or creatinine ≥ 3.5 mg/dL without continuous renal replacement therapy (CRRT), or requires acute post-operative dialysis
  • Has an active malignancy (defined as requiring chemotherapy, radiation, and/or surgical intervention within 90 days prior to study entry) (excluding non-melanoma skin cancer)
  • Has known AIDS
  • Has a terminal illness (life expectancy < 7 days)
  • Has undergone organ transplantation
  • Has received PN with lipid within 48 hours prior to study entry
  • Has mental disability to understand the scope and possible consequences of the study and the legally authorized representative is unavailable
  • Has a baseline serum triglyceride > 400 mg/dL

Sites / Locations

  • Grady Memorial Hospital
  • Emory University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Intralipid 20% Intravenous Emulsion

ClinOleic 20% Intravenous Emulsion

Arm Description

Subjects who require Total Parenteral Nutrition TPN receiving Intralipid 20% (soybean-based)

Subjects who require Total Parenteral Nutrition TPN receiving ClinOleic 20% (olive oil based)

Outcomes

Primary Outcome Measures

Number of New Nosocomial Infections After 48 Hrs of Parenteral Nutrition (PN) Between the 2 Groups During Their Hospital Stay
New nosocomial infections, defined as culture-proven infection including wound, drain, bloodstream, respiratory tract, and urinary tract infections during PN. The presence of nosocomial infections was diagnosed based on standardized Centers for Disease Control (CDC) guidelines for laboratory-confirmed bloodstream infection and did not distinguish catheter-related infections per se. The following daily information was evaluated by the study team for nosocomial infection surveillance: temperature (fever)curve, white blood cell counts, review of daily progress notes in the medical record, daily clinical microbiology laboratory culture data, orders for antimicrobial agents (agent, daily dose, and start/stop times will be recorded), review of all relevant dictated radiographic reports (e.g., chest radiographs, abdominal computer tomography), communication, as needed, with primary physicians and site infectious disease consultants, and use of the CDC guidelines.

Secondary Outcome Measures

Number of Days Patients Stayed in ICU During Parenteral Nutrition Between Treatment Groups
The mean number of days patients stayed in the intensive care unit between the Intralipid 20% and ClinOleic 20% while they are on parenteral nutrition is calculated and compared
Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured
Peripheral blood samples will be analyzed for circulating levels of inflammatory markers markers like plasma C-reactive protein (CRP) at baseline, day 3, and day 7 of soybean oil- and olive oil-based parenteral nutrition infusion and compared. A reading of less than 1 mg/L indicates low risk; a reading between 1 and 2.9 mg/L indicates intermediate risk; a reading greater than 3 mg/L indicates high risk and a reading above 10 mg/L indicates a need for further testing. Since the patients are sick and hospitalized, it is expected that their levels are elevated compared to normal subjects. The levels between the 2 groups are compared to see if there is any difference.Levels were measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the Immulite analyzer.
Mean Plasma Concentration of Tumor Necrosis Factor-alpha, in pg/mL is Measured Between the Two Treatment Groups
Plasma concentration of circulating levels of inflammatory stress markers like tumor necrosis factor-alpha is measured at baseline, day 3, and day 7 among soybean oil- and olive oil-based parenteral nutrition infusion groups. The normal reference values are < or =2.8 pg/mL. Levels were measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the Immulite analyzer.
Mean Change in Plasma Concentration of Cystine in Micromol Per Liter at Baseline, Day 3 and Day 7 Among the Treatment Groups
Mean Plasma concentration of circulating levels of oxidative stress markers like levels of cystine at baseline, day 3, and day 7 are measured and compared between the soybean oil- and olive oil-based parenteral nutrition infusion groups. Levels were measured using iodoacetate to alkylate free thiols, derivatization with dansyl chloride to fluorescently tag amino groups, and high pressure liquid chromatography (HPLC) and fluorescence to separate, detect, and quantify the molecules.
Mean Hospital Blood Glucose (mg/dL) in Diabetic Patients is Measured During Parenteral Nutrition Between the Two Treatment Groups
Mean hospital blood glucose is measured as an indicator for insulin sensitivity. Capillary blood glucose was measured with a glucose meter at bedside during PN infusion. For this study normal blood glucose levels were indicated as 70-200 mg/dL, any blood glucose level < 70 mg/dL is regarded as hypoglycemia and above 200 mg/dL is regarded as hyperglycemia.
Number of Deaths During Parenteral Nutrition Treatment Between Two Treatment Groups During Hospitalization
Mortality is defined as death occurring during admission, either during the time PN is received or after PN treatment is completed. Death during hospitalization rather than during PN treatment was chosen because many patients who undergo treatment with PN die or develop hospital complications within a period of several days after treatment cessation. The number of deaths between the two groups are compared.
Mean Change in Percentage of Granulocyte Phagocytosis After 7-day Administration of Parenteral Nutrition Between the Two Treatment Groups
Change in immune function is assessed by percentage of Granulocyte phagocytosis after 7-day administration of parenteral nutrition between the two treatment groups. The phagocytic and oxidative burst activity of monocytes and granulocytes in heparinized whole blood was assessed according to manufacturer's instructions using specific reagent kits for this purpose at baseline and again at day 7. Briefly, granulocyte phagocytic activity was quantitated by incubation of whole blood with fluorescein isothiocyanate-labeled, opsonized Escherichia coli bacteria at 37°C with detection of fluorescence of internalized particles as a percentage of positive cells by flow cytometry.

Full Information

First Posted
April 18, 2008
Last Updated
September 20, 2018
Sponsor
Emory University
Collaborators
Baxter Healthcare Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00672854
Brief Title
Study Comparing a Soybean Oil-Based With an Olive Oil-Based Lipid Emulsion in ICU Patients Requiring TPN
Acronym
TPN2
Official Title
Study Comparing a Soybean Oil-Based vs Olive Oil-Based Lipid Emulsion: Effects on Endothelial Function, Inflammatory Markers, Oxidative Stress, Immune Function,Insulin Sensitivity and Carb Metabolism Intensive Care Unit Patients
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
November 2008 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
Baxter Healthcare Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Many hospitalized patients who are malnourished or not eating receive intravenous feeding or total parenteral nutrition (TPN). Despite improving nutrition, TPN may increase the risk of infections and hospital complications. We do not know why TPN increases hospital complications, but it may be caused by the high sugar or fat content in TPN solutions.
Detailed Description
This study compares the effect of a soybean oil-based versus an olive oil-based lipid emulsion in healthy volunteers and in critically ill patients. In healthy volunteers, your blood sugar levels, blood vessel function, and your ability to fight infections will be examined. In ICU patients, we examines whether use of the olive oil-based lipid emulsion may decrease the risk of infection and hospital complications.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parenteral Nutrition
Keywords
parenteral nutrition, lipid emulsion, nosocomial infection, mortality, endothelial function, inflammatory markers, oxidative stress, immune function, autonomic nervous system, insulin sensitivity, carbohydrate metabolism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intralipid 20% Intravenous Emulsion
Arm Type
Active Comparator
Arm Description
Subjects who require Total Parenteral Nutrition TPN receiving Intralipid 20% (soybean-based)
Arm Title
ClinOleic 20% Intravenous Emulsion
Arm Type
Experimental
Arm Description
Subjects who require Total Parenteral Nutrition TPN receiving ClinOleic 20% (olive oil based)
Intervention Type
Drug
Intervention Name(s)
ClinOleic 20% Intravenous Emulsion
Other Intervention Name(s)
Lipid Emulsion
Intervention Description
ClinOleic 20% is a lipid emulsion containing a mixture of refined olive oil (approximately 80%) and refined soybean oil (approximately 20%) corresponding to an essential fatty acid intake of approximately 20% of the total fatty acids intake.
Intervention Type
Drug
Intervention Name(s)
Intralipid, 20% Intravenous Emulsion
Other Intervention Name(s)
20% i.v. fat emulsion
Intervention Description
It is made up of 20% Soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin, and water for injection
Primary Outcome Measure Information:
Title
Number of New Nosocomial Infections After 48 Hrs of Parenteral Nutrition (PN) Between the 2 Groups During Their Hospital Stay
Description
New nosocomial infections, defined as culture-proven infection including wound, drain, bloodstream, respiratory tract, and urinary tract infections during PN. The presence of nosocomial infections was diagnosed based on standardized Centers for Disease Control (CDC) guidelines for laboratory-confirmed bloodstream infection and did not distinguish catheter-related infections per se. The following daily information was evaluated by the study team for nosocomial infection surveillance: temperature (fever)curve, white blood cell counts, review of daily progress notes in the medical record, daily clinical microbiology laboratory culture data, orders for antimicrobial agents (agent, daily dose, and start/stop times will be recorded), review of all relevant dictated radiographic reports (e.g., chest radiographs, abdominal computer tomography), communication, as needed, with primary physicians and site infectious disease consultants, and use of the CDC guidelines.
Time Frame
2 days after Parenteral Nutrition (up to 28 days post randomization)
Secondary Outcome Measure Information:
Title
Number of Days Patients Stayed in ICU During Parenteral Nutrition Between Treatment Groups
Description
The mean number of days patients stayed in the intensive care unit between the Intralipid 20% and ClinOleic 20% while they are on parenteral nutrition is calculated and compared
Time Frame
During Parenteral Nutrition (up to 28 days post randomization)
Title
Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured
Description
Peripheral blood samples will be analyzed for circulating levels of inflammatory markers markers like plasma C-reactive protein (CRP) at baseline, day 3, and day 7 of soybean oil- and olive oil-based parenteral nutrition infusion and compared. A reading of less than 1 mg/L indicates low risk; a reading between 1 and 2.9 mg/L indicates intermediate risk; a reading greater than 3 mg/L indicates high risk and a reading above 10 mg/L indicates a need for further testing. Since the patients are sick and hospitalized, it is expected that their levels are elevated compared to normal subjects. The levels between the 2 groups are compared to see if there is any difference.Levels were measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the Immulite analyzer.
Time Frame
Baseline, Day 3 and Day 7
Title
Mean Plasma Concentration of Tumor Necrosis Factor-alpha, in pg/mL is Measured Between the Two Treatment Groups
Description
Plasma concentration of circulating levels of inflammatory stress markers like tumor necrosis factor-alpha is measured at baseline, day 3, and day 7 among soybean oil- and olive oil-based parenteral nutrition infusion groups. The normal reference values are < or =2.8 pg/mL. Levels were measured in plasma using a solid phase, two-site sequential chemiluminescent immunometric assays on the Immulite analyzer.
Time Frame
Baseline, Day 3 and Day 7
Title
Mean Change in Plasma Concentration of Cystine in Micromol Per Liter at Baseline, Day 3 and Day 7 Among the Treatment Groups
Description
Mean Plasma concentration of circulating levels of oxidative stress markers like levels of cystine at baseline, day 3, and day 7 are measured and compared between the soybean oil- and olive oil-based parenteral nutrition infusion groups. Levels were measured using iodoacetate to alkylate free thiols, derivatization with dansyl chloride to fluorescently tag amino groups, and high pressure liquid chromatography (HPLC) and fluorescence to separate, detect, and quantify the molecules.
Time Frame
Baseline, Day 3 and Day 7
Title
Mean Hospital Blood Glucose (mg/dL) in Diabetic Patients is Measured During Parenteral Nutrition Between the Two Treatment Groups
Description
Mean hospital blood glucose is measured as an indicator for insulin sensitivity. Capillary blood glucose was measured with a glucose meter at bedside during PN infusion. For this study normal blood glucose levels were indicated as 70-200 mg/dL, any blood glucose level < 70 mg/dL is regarded as hypoglycemia and above 200 mg/dL is regarded as hyperglycemia.
Time Frame
During Parenteral Nutrition (up to 28 days post randomization)
Title
Number of Deaths During Parenteral Nutrition Treatment Between Two Treatment Groups During Hospitalization
Description
Mortality is defined as death occurring during admission, either during the time PN is received or after PN treatment is completed. Death during hospitalization rather than during PN treatment was chosen because many patients who undergo treatment with PN die or develop hospital complications within a period of several days after treatment cessation. The number of deaths between the two groups are compared.
Time Frame
During Parenteral Nutrition (up to 28 days post randomization)
Title
Mean Change in Percentage of Granulocyte Phagocytosis After 7-day Administration of Parenteral Nutrition Between the Two Treatment Groups
Description
Change in immune function is assessed by percentage of Granulocyte phagocytosis after 7-day administration of parenteral nutrition between the two treatment groups. The phagocytic and oxidative burst activity of monocytes and granulocytes in heparinized whole blood was assessed according to manufacturer's instructions using specific reagent kits for this purpose at baseline and again at day 7. Briefly, granulocyte phagocytic activity was quantitated by incubation of whole blood with fluorescein isothiocyanate-labeled, opsonized Escherichia coli bacteria at 37°C with detection of fluorescence of internalized particles as a percentage of positive cells by flow cytometry.
Time Frame
Baseline and 7 days post randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Age: 18 - 80 years when initiating PN In medical/surgical ICU Has central venous access to administer PN Anticipated to receive PN ≥ 5 days Exclusion criteria: Enrolled in an investigative study within the last 30 days prior to study entry Female patients: pregnant or breast feeding Has clinical sepsis (defined as mean arterial pressure (MAP) < 60 mmHg on ≥ 2 occasions and unstable BP despite pressor support) within 24 hours prior to study entry Has known cirrhosis or total bilirubin ≥ 10.0 mg/dL Has chronic renal failure (defined as requirement for hemodialysis or peritoneal dialysis therapy), or creatinine ≥ 3.5 mg/dL without continuous renal replacement therapy (CRRT), or requires acute post-operative dialysis Has an active malignancy (defined as requiring chemotherapy, radiation, and/or surgical intervention within 90 days prior to study entry) (excluding non-melanoma skin cancer) Has known AIDS Has a terminal illness (life expectancy < 7 days) Has undergone organ transplantation Has received PN with lipid within 48 hours prior to study entry Has mental disability to understand the scope and possible consequences of the study and the legally authorized representative is unavailable Has a baseline serum triglyceride > 400 mg/dL
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo Umpierrez, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Emory University Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22488002
Citation
Umpierrez GE, Spiegelman R, Zhao V, Smiley DD, Pinzon I, Griffith DP, Peng L, Morris T, Luo M, Garcia H, Thomas C, Newton CA, Ziegler TR. A double-blind, randomized clinical trial comparing soybean oil-based versus olive oil-based lipid emulsions in adult medical-surgical intensive care unit patients requiring parenteral nutrition. Crit Care Med. 2012 Jun;40(6):1792-8. doi: 10.1097/CCM.0b013e3182474bf9.
Results Reference
result

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Study Comparing a Soybean Oil-Based With an Olive Oil-Based Lipid Emulsion in ICU Patients Requiring TPN

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