Parenteral Nutrition
Conditions
Keywords
parenteral nutrition, lipid emulsion, nosocomial infection, mortality, endothelial function, inflammatory markers, oxidative stress, immune function, autonomic nervous system, insulin sensitivity, carbohydrate metabolism
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.
Interventions
DRUGClinOleic 20% Intravenous Emulsion
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.
It is made up of 20% Soybean oil, 1.2% egg yolk phospholipids, 2.25% glycerin, and water for injection
Sponsors
Baxter Healthcare Corporation
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of New Nosocomial Infections After 48 Hrs of Parenteral Nutrition (PN) Between the 2 Groups During Their Hospital Stay | 2 days after Parenteral Nutrition (up to 28 days post randomization) | 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
| Measure | Time frame | Description |
|---|---|---|
| Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured | Baseline, Day 3 and Day 7 | 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 | Baseline, Day 3 and Day 7 | 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 | Baseline, Day 3 and Day 7 | 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. |
| Number of Days Patients Stayed in ICU During Parenteral Nutrition Between Treatment Groups | During Parenteral Nutrition (up to 28 days post randomization) | 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 |
| Number of Deaths During Parenteral Nutrition Treatment Between Two Treatment Groups During Hospitalization | During Parenteral Nutrition (up to 28 days post randomization) | 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 | Baseline and 7 days post randomization | 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. |
| Mean Hospital Blood Glucose (mg/dL) in Diabetic Patients is Measured During Parenteral Nutrition Between the Two Treatment Groups | During Parenteral Nutrition (up to 28 days post randomization) | 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at Grady Memorial Hospital, a major urban teaching hospital affiliated with Emory University and at Emory University Hospital, a tertiary referral academic institution in Atlanta, Georgia.
Pre-assignment details
A total of 100 patients were randomized to either soybean oil-based (intralipid 20%) parenteral nutrition or olive oil-based (ClinOleic 20%) parenteral nutrition for up to 28 days. A total of 49 patients received soybean oil-based parenteral nutrition and a total of 51 patients received olive oil-based lipid emulsion in parenteral nutrition
Participants by arm
| Arm | Count |
|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% TPN subjects receive Intralipid (soybean-based)
Intralipid: TPN with Intralipid (20%) | 49 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% TPN subjects receive ClinOleic 20% (olive oil based)
ClinOleic: TPN with ClinOleic (20%) | 51 |
| Total | 100 |
Baseline characteristics
| Characteristic | Total Parenteral Nutrition (TPN) Given Intralipid 20% | Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 16 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 35 Participants | 71 Participants |
| Age, Continuous | 51.3 years STANDARD_DEVIATION 15 | 46.4 years STANDARD_DEVIATION 19 | 48.9 years STANDARD_DEVIATION 17 |
| Sex: Female, Male Female | 22 Participants | 23 Participants | 45 Participants |
| Sex: Female, Male Male | 27 Participants | 28 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 49 | 4 / 51 |
| other Total, other adverse events | 2 / 49 | 3 / 51 |
| serious Total, serious adverse events | 33 / 49 | 44 / 51 |
Outcome results
Primary
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.
Time frame: 2 days after Parenteral Nutrition (up to 28 days post randomization)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Number of New Nosocomial Infections After 48 Hrs of Parenteral Nutrition (PN) Between the 2 Groups During Their Hospital Stay | 21 number of nosocomial infections |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Number of New Nosocomial Infections After 48 Hrs of Parenteral Nutrition (PN) Between the 2 Groups During Their Hospital Stay | 29 number of nosocomial infections |
Secondary
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.
Time frame: Baseline and 7 days post randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Change in Percentage of Granulocyte Phagocytosis After 7-day Administration of Parenteral Nutrition Between the Two Treatment Groups | 3.86 percentage of phagocytosis | Standard Deviation 18.8 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Change in Percentage of Granulocyte Phagocytosis After 7-day Administration of Parenteral Nutrition Between the Two Treatment Groups | 6.36 percentage of phagocytosis | Standard Deviation 38.4 |
Secondary
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.
Time frame: Baseline, Day 3 and Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Change in Plasma Concentration of Cystine in Micromol Per Liter at Baseline, Day 3 and Day 7 Among the Treatment Groups | Baseline | 82.22 micromol per liter | Standard Deviation 43.74 |
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Change in Plasma Concentration of Cystine in Micromol Per Liter at Baseline, Day 3 and Day 7 Among the Treatment Groups | Day 3 | 88.65 micromol per liter | Standard Deviation 39.09 |
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Change in Plasma Concentration of Cystine in Micromol Per Liter at Baseline, Day 3 and Day 7 Among the Treatment Groups | Day 7 | 90.06 micromol per liter | Standard Deviation 42.28 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Change in Plasma Concentration of Cystine in Micromol Per Liter at Baseline, Day 3 and Day 7 Among the Treatment Groups | Baseline | 75.8 micromol per liter | Standard Deviation 31.09 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Change in Plasma Concentration of Cystine in Micromol Per Liter at Baseline, Day 3 and Day 7 Among the Treatment Groups | Day 3 | 93.54 micromol per liter | Standard Deviation 36.04 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Change in Plasma Concentration of Cystine in Micromol Per Liter at Baseline, Day 3 and Day 7 Among the Treatment Groups | Day 7 | 87.7 micromol per liter | Standard Deviation 42.04 |
Secondary
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.
Time frame: During Parenteral Nutrition (up to 28 days post randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Hospital Blood Glucose (mg/dL) in Diabetic Patients is Measured During Parenteral Nutrition Between the Two Treatment Groups | 128.4 mg/dL | Standard Deviation 6 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Hospital Blood Glucose (mg/dL) in Diabetic Patients is Measured During Parenteral Nutrition Between the Two Treatment Groups | 125 mg/dL | Standard Deviation 9 |
Secondary
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.
Time frame: Baseline, Day 3 and Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured | Baseline | 169.67 mg/L | Standard Deviation 125.05 |
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured | Day 3 | 109.48 mg/L | Standard Deviation 58.42 |
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured | Day 7 | 122.71 mg/L | Standard Deviation 80.68 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured | Baseline | 152.45 mg/L | Standard Deviation 123.09 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured | Day 3 | 115.33 mg/L | Standard Deviation 66.8 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Plasma Concentration of C-reactive Protein in mg/L at Baseline, Day 3 and Day 7 Among the Treatment Groups Will be Measured | Day 7 | 146.63 mg/L | Standard Deviation 115 |
Secondary
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.
Time frame: Baseline, Day 3 and Day 7
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Plasma Concentration of Tumor Necrosis Factor-alpha, in pg/mL is Measured Between the Two Treatment Groups | Baseline | 0.12 pg/mL | Standard Deviation 0.08 |
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Plasma Concentration of Tumor Necrosis Factor-alpha, in pg/mL is Measured Between the Two Treatment Groups | Day 3 | 0.12 pg/mL | Standard Deviation 0.05 |
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Mean Plasma Concentration of Tumor Necrosis Factor-alpha, in pg/mL is Measured Between the Two Treatment Groups | Day 7 | 0.10 pg/mL | Standard Deviation 0.04 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Plasma Concentration of Tumor Necrosis Factor-alpha, in pg/mL is Measured Between the Two Treatment Groups | Baseline | 0.09 pg/mL | Standard Deviation 0.03 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Plasma Concentration of Tumor Necrosis Factor-alpha, in pg/mL is Measured Between the Two Treatment Groups | Day 3 | 0.09 pg/mL | Standard Deviation 0.03 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Mean Plasma Concentration of Tumor Necrosis Factor-alpha, in pg/mL is Measured Between the Two Treatment Groups | Day 7 | 0.10 pg/mL | Standard Deviation 0.07 |
Secondary
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
Time frame: During Parenteral Nutrition (up to 28 days post randomization)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Number of Days Patients Stayed in ICU During Parenteral Nutrition Between Treatment Groups | 15.2 days | Standard Deviation 14 |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Number of Days Patients Stayed in ICU During Parenteral Nutrition Between Treatment Groups | 17 days | Standard Deviation 18 |
Secondary
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.
Time frame: During Parenteral Nutrition (up to 28 days post randomization)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Total Parenteral Nutrition (TPN) Given Intralipid 20% | Number of Deaths During Parenteral Nutrition Treatment Between Two Treatment Groups During Hospitalization | 5 participants |
| Total Parenteral Nutrition (TPN) Given ClinOleic 20% | Number of Deaths During Parenteral Nutrition Treatment Between Two Treatment Groups During Hospitalization | 4 participants |