Trial Outcomes & Findings for Study Comparing a Soybean Oil-Based With an Olive Oil-Based Lipid Emulsion in ICU Patients Requiring TPN (NCT NCT00672854)

NCT ID: NCT00672854

Last Updated: 2018-10-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 100 participants
• Primary outcome timeframe: 2 days after Parenteral Nutrition (up to 28 days post randomization)
• Results posted on: 2018-10-17

Participant Flow

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.

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

Participant milestones

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% TPN subjects receive Intralipid (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% TPN subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (20%)
Overall Study STARTED	49	51
Overall Study COMPLETED	49	51
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants TPN subjects receive Intralipid (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants TPN subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (20%)	Total n=100 Participants Total of all reporting groups
Age, Continuous	51.3 years STANDARD_DEVIATION 15 • n=5 Participants	46.4 years STANDARD_DEVIATION 19 • n=7 Participants	48.9 years STANDARD_DEVIATION 17 • n=5 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Age, Categorical >=65 years	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	23 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	28 Participants n=7 Participants	55 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants Total Parenteral Nutrition (TPN) subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants Total Parenteral Nutrition (TPN) subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (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	29 number of nosocomial infections

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants Total Parenteral Nutrition (TPN) subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants Total Parenteral Nutrition (TPN) subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (20%)
Number of Days Patients Stayed in ICU During Parenteral Nutrition Between Treatment Groups	15.2 days Standard Deviation 14	17 days Standard Deviation 18

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants Total Parenteral Nutrition (TPN) subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants Total Parenteral Nutrition (TPN) subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with 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	169.67 mg/L Standard Deviation 125.05	152.45 mg/L Standard Deviation 123.09
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	115.33 mg/L Standard Deviation 66.80
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	146.63 mg/L Standard Deviation 115

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants Total Parenteral Nutrition (TPN) subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants Total Parenteral Nutrition (TPN) subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (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	0.09 pg/mL Standard Deviation 0.03
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	0.09 pg/mL Standard Deviation 0.03
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	0.10 pg/mL Standard Deviation 0.07

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants Total Parenteral Nutrition (TPN) subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants Total Parenteral Nutrition (TPN) subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with 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	82.22 micromol per liter Standard Deviation 43.74	75.8 micromol per liter Standard Deviation 31.09
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	93.54 micromol per liter Standard Deviation 36.04
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	87.7 micromol per liter Standard Deviation 42.04

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants Total Parenteral Nutrition (TPN) subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants Total Parenteral Nutrition (TPN) subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (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	125 mg/dL Standard Deviation 9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants Total Parenteral Nutrition (TPN) subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants Total Parenteral Nutrition (TPN) subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (20%)
Number of Deaths During Parenteral Nutrition Treatment Between Two Treatment Groups During Hospitalization	5 participants	4 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 Participants Total Parenteral Nutrition (TPN) subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 Participants Total Parenteral Nutrition (TPN) subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (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	6.36 percentage of phagocytosis Standard Deviation 38.4

Adverse Events

Total Parenteral Nutrition (TPN) Given Intralipid 20%

Serious events: 33 serious events

Other events: 2 other events

Deaths: 5 deaths

Total Parenteral Nutrition (TPN) Given ClinOleic 20%

Serious events: 44 serious events

Other events: 3 other events

Deaths: 4 deaths

Serious adverse events

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 participants at risk TPN subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 participants at risk TPN subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (20%)
Respiratory, thoracic and mediastinal disorders Pneumonia	10.2% 5/49 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study	13.7% 7/51 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study
Renal and urinary disorders Urinary tract infection,	14.3% 7/49 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study	13.7% 7/51 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study
Blood and lymphatic system disorders Bacteremia	22.4% 11/49 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study	21.6% 11/51 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study
Skin and subcutaneous tissue disorders Wound infection,	8.2% 4/49 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study	21.6% 11/51 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study
Cardiac disorders Acute myocardial infarction,	0.00% 0/49 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study	3.9% 2/51 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study
Cardiac disorders Congestive heart failure,	2.0% 1/49 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study	3.9% 2/51 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study
Cardiac disorders Cardiac arrhythmia,	10.2% 5/49 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study	11.8% 6/51 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study

Other adverse events

Measure	Total Parenteral Nutrition (TPN) Given Intralipid 20% n=49 participants at risk TPN subjects receive Intralipid 20% (soybean-based) Intralipid: TPN with Intralipid (20%)	Total Parenteral Nutrition (TPN) Given ClinOleic 20% n=51 participants at risk TPN subjects receive ClinOleic 20% (olive oil based) ClinOleic: TPN with ClinOleic (20%)
Surgical and medical procedures Vein irritation	4.1% 2/49 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study	5.9% 3/51 • The adverse events were calculated up to 28 days post randomization and on parenteral nutrition between the two treatment groups Since the subjects enrolled are already hospitalized patients in the Intensive care unit, main adverse events of interest were serious adverse events and deaths are captured for the study

Additional Information

Guillermo Umpierrez

Emory University

Phone: 404-778-1665

Email: geumpie@emory.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place