Trial Outcomes & Findings for The Effect of Lipid Emulsions on Free Fatty Acids and Free Bilirubin in Premature Newborns (NCT NCT03857646)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

66 participants

Primary outcome timeframe

first day of infusion at 3 g/kg/day

Results posted on

2025-03-03

Participant Flow

Participant milestones

Participant milestones
Measure	Intralipid Intralipid, 20% Intravenous Emulsion: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	Soybean Oil Medium-chain Triglycerides Olive Oil Fish Oil (SMOF) Lipid Soybean oil Medium-chain triglycerides Olive oil Fish Oil (SMOF) lipid: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.
Overall Study STARTED	33	33
Overall Study Completed One Day of Infusion at 3 g/kg/Day	31	29
Overall Study Completed Two Days of Infusion at 3 g/kg/Day	29	25
Overall Study COMPLETED	29	25
Overall Study NOT COMPLETED	4	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Data was not collected for one participant in the Intralipid arm. Data was not collected for one participant in the SMOF lipid arm.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intralipid n=33 Participants Intralipid, 20% Intravenous Emulsion: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	SMOF Lipid n=33 Participants SMOF lipid: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	Total n=66 Participants Total of all reporting groups
Age, Continuous	1.81 days STANDARD_DEVIATION 0.53 • n=32 Participants • Data was not collected for one participant in the Intralipid arm. Data was not collected for one participant in the SMOF lipid arm.	1.83 days STANDARD_DEVIATION 0.37 • n=32 Participants • Data was not collected for one participant in the Intralipid arm. Data was not collected for one participant in the SMOF lipid arm.	1.82 days STANDARD_DEVIATION 0.45 • n=64 Participants • Data was not collected for one participant in the Intralipid arm. Data was not collected for one participant in the SMOF lipid arm.
Sex: Female, Male Female	18 Participants n=33 Participants	18 Participants n=33 Participants	36 Participants n=66 Participants
Sex: Female, Male Male	15 Participants n=33 Participants	15 Participants n=33 Participants	30 Participants n=66 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: first day of infusion at 3 g/kg/day

Population: UB levels were measured in 2/3 of the samples before the pandemic closed the analytic laboratory, and the other 1/3 were assessed post-pandemic 1.5 years later. The UB data are invalid due to an issue associated with the delay, that is, the UB measurement device developed by the bench scientist colleagues was recalibrated in the interim such that the UB results pre vs post recalibration are incomparable. Data were not collected for 1 participant in the Intralipid arm.

Outcome measures

Outcome measures
Measure	Intralipid n=30 Participants Intralipid, 20% Intravenous Emulsion: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	SMOF Lipid n=29 Participants SMOF lipid: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.
Free Bilirubin (UB) Serum Levels	10.5 Nanomoles/Liter (nM) Standard Deviation 7.5	9.4 Nanomoles/Liter (nM) Standard Deviation 7.0

PRIMARY outcome

Timeframe: second day of infusion at 3 g/kg/day

Population: UB levels were measured in 2/3 of the samples before the pandemic closed the analytic laboratory, and the other 1/3 were assessed post-pandemic 1.5 years later. The UB data are invalid due to an issue associated with the delay, that is, the UB measurement device developed by the bench scientist colleagues was recalibrated in the interim such that the UB results pre vs post recalibration are incomparable.

Outcome measures

Outcome measures
Measure	Intralipid n=29 Participants Intralipid, 20% Intravenous Emulsion: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	SMOF Lipid n=25 Participants SMOF lipid: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.
Free Bilirubin (UB) Serum Levels	10.2 Nanomoles/Liter (nM) Standard Deviation 7.8	7.4 Nanomoles/Liter (nM) Standard Deviation 2.2

SECONDARY outcome

Timeframe: first day of infusion at 3 g/kg/day

Population: FFAu levels were measured in 2/3 of the samples before the pandemic closed the analytic laboratory, and the other 1/3 were assessed post-pandemic 1.5 years later. The FFAu data are invalid due to an issue associated with the delay, that is, there was severe sample degradation of the FFAu samples that were measured post-pandemic due to prolonged freezing and refreezing-rethawing.

To measure unbound free fatty acid level, a fluorescent probe called Acrylodan-Labeled Intestinal Fatty Acid Binding Protein 2 (ADIFAB2) was used. The ADIFAB2 fluorescent probe is a fatty acid binding protein complexed with a fluorescent group. Once mixed with a sample, the ADIFAB2 fluorescent probe binds all unbound free fatty acid in the sample; therefore, measurement of fluorescence indicates the amount of unbound free fatty acid in the sample. After binding of the ADIFAB2 fluorescent probe to the sample, fluorescence intensities are measured at two wavelengths (550 nanometers and 457 nanometers), and for this outcome measure the R value is reported. The R value is the ratio of the fluorescence intensity at 550 nanometers to the fluorescence intensity at 457 nanometers.

Outcome measures

Outcome measures
Measure	Intralipid n=31 Participants Intralipid, 20% Intravenous Emulsion: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	SMOF Lipid n=29 Participants SMOF lipid: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.
Unbound Free Fatty Acid (FFAu) Serum Level	0.112 ratio value (R) Standard Deviation 0.034	0.106 ratio value (R) Standard Deviation 0.008

SECONDARY outcome

Timeframe: second day of infusion at 3 g/kg/day

Population: FFAu levels were measured in 2/3 of the samples before the pandemic closed the analytic laboratory, and the other 1/3 were assessed post-pandemic 1.5 years later. The FFAu data are invalid due to an issue associated with the delay, that is, there was severe sample degradation of the FFAu samples that were measured post-pandemic due to prolonged freezing and refreezing-rethawing.

To measure unbound free fatty acid level, a fluorescent probe called ADIFAB2 was used. The ADIFAB2 fluorescent probe is a fatty acid binding protein complexed with a fluorescent group. Once mixed with a sample, the ADIFAB2 fluorescent probe binds all unbound free fatty acid in the sample; therefore, measurement of fluorescence indicates the amount of unbound free fatty acid in the sample. After binding of the ADIFAB2 fluorescent probe to the sample, fluorescence intensities are measured at two wavelengths (550 nanometers and 457 nanometers), and for this outcome measure the R value is reported. The R value is the ratio of the fluorescence intensity at 550 nanometers to the fluorescence intensity at 457 nanometers.

Outcome measures

Outcome measures
Measure	Intralipid n=29 Participants Intralipid, 20% Intravenous Emulsion: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	SMOF Lipid n=25 Participants SMOF lipid: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.
Unbound Free Fatty Acid (FFAu) Serum Level	0.105 ratio value (R) Standard Deviation 0.008	0.105 ratio value (R) Standard Deviation 0.008

Adverse Events

Intralipid

Serious events: 2 serious events

Other events: 0 other events

Deaths: 2 deaths

SMOF Lipid

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Intralipid n=33 participants at risk Intralipid, 20% Intravenous Emulsion: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	SMOF Lipid n=33 participants at risk SMOF lipid: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.
General disorders Death	6.1% 2/33 • Number of events 2 • about 5 days	3.0% 1/33 • Number of events 1 • about 5 days
Vascular disorders Severe intraventricular hemorrhage (IVH)	0.00% 0/33 • about 5 days	3.0% 1/33 • Number of events 1 • about 5 days

Other adverse events

Other adverse events
Measure	Intralipid n=33 participants at risk Intralipid, 20% Intravenous Emulsion: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.	SMOF Lipid n=33 participants at risk SMOF lipid: Lipids start at 1 g/kg/day and advance by 1 g/kg/day to a maximum of 3 g/kg/day as tolerated by the the neonate.
Vascular disorders Received vasopressors to treat low blood pressure	0.00% 0/33 • about 5 days	3.0% 1/33 • Number of events 1 • about 5 days

Additional Information

Cody Arnold

Stanford University

Phone: (650) 723-8772

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place