Trial Outcomes & Findings for Cholestasis Reversal: Efficacy of IV Fish Oil (NCT NCT00910104)
NCT ID: NCT00910104
Last Updated: 2024-09-19
Results Overview
Time to reversal of established parenteral nutrition associated liver disease, defined as a decrease in direct bilirubin to \<= 2.0 mg/dL.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
91 participants
Primary outcome timeframe
Duration of treatment
Results posted on
2024-09-19
Participant Flow
Between August 2006 and November 2007, 42 patients with IFALD were prospectively enrolled to receive compassionate use open label treatment with 10% FOLE (Omegaven®) as part of their PN. For comparison, retrospective data were retrieved for 49 historical control patients who had received 20% SOLE (Intralipid® 20%) as part of their PN between 1999 and 2006. Patients in both treatment arms were required to have a direct bilirubin level \>=2mg/dL upon initiation of their respective lipid emulsion.
Participant milestones
| Measure |
Omegaven
1g/kg/day for duration of study participation for all participants.
Omegaven®: 10% Omegaven® 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated.
|
Intralipid
Intralipid®: 20% Intralipid® up to 3g/kg/day, IV (in the vein).
|
|---|---|---|
|
Overall Study
STARTED
|
42
|
49
|
|
Overall Study
COMPLETED
|
42
|
49
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and ethnicity not reliably obtained on all subjects.
Baseline characteristics by cohort
| Measure |
Omegaven
n=42 Participants
1g/kg/day for duration of study participation for all participants
Omegaven®: 10% Omegaven® 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated
|
Intralipid (Historical Control)
n=49 Participants
Patients who received Intralipid between 1999-2006 and whose direct bilirubin was ever \>=2.0 mg/dL.
|
Total
n=91 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
42 Participants
n=42 Participants
|
49 Participants
n=49 Participants
|
91 Participants
n=91 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=42 Participants
|
0 Participants
n=49 Participants
|
0 Participants
n=91 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=42 Participants
|
0 Participants
n=49 Participants
|
0 Participants
n=91 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=42 Participants
|
18 Participants
n=49 Participants
|
32 Participants
n=91 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=42 Participants
|
31 Participants
n=49 Participants
|
59 Participants
n=91 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=42 Participants • Race and ethnicity not reliably obtained on all subjects.
|
1 Participants
n=49 Participants • Race and ethnicity not reliably obtained on all subjects.
|
9 Participants
n=91 Participants • Race and ethnicity not reliably obtained on all subjects.
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=42 Participants • Race and ethnicity not reliably obtained on all subjects.
|
34 Participants
n=49 Participants • Race and ethnicity not reliably obtained on all subjects.
|
67 Participants
n=91 Participants • Race and ethnicity not reliably obtained on all subjects.
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=42 Participants • Race and ethnicity not reliably obtained on all subjects.
|
14 Participants
n=49 Participants • Race and ethnicity not reliably obtained on all subjects.
|
15 Participants
n=91 Participants • Race and ethnicity not reliably obtained on all subjects.
|
|
Direct bilirubin
|
5.5 mg/dL
n=38 Participants • Patients who were transferred to Boston Children's after starting Omegaven elsewhere do not have a baseline direct bilirubin available.
|
3.3 mg/dL
n=49 Participants • Patients who were transferred to Boston Children's after starting Omegaven elsewhere do not have a baseline direct bilirubin available.
|
3.9 mg/dL
n=87 Participants • Patients who were transferred to Boston Children's after starting Omegaven elsewhere do not have a baseline direct bilirubin available.
|
|
Duration of PN before enrollment (d), median (IQR)
|
63 Days
n=38 Participants • PN start date is unknown for n=4 in the fish oil-emulsion arm and n=2 in the soybean oil-emulsion arm.
|
40 Days
n=47 Participants • PN start date is unknown for n=4 in the fish oil-emulsion arm and n=2 in the soybean oil-emulsion arm.
|
54 Days
n=85 Participants • PN start date is unknown for n=4 in the fish oil-emulsion arm and n=2 in the soybean oil-emulsion arm.
|
PRIMARY outcome
Timeframe: Duration of treatmentPopulation: The primary efficacy end-point was time to reversal of cholestasis (direct bilirubin \<= 2.0 mg/dL).
Time to reversal of established parenteral nutrition associated liver disease, defined as a decrease in direct bilirubin to \<= 2.0 mg/dL.
Outcome measures
| Measure |
Omegaven
n=42 Participants
1g/kg/day for duration of study participation for all participants
Omegaven®: 10% Omegaven® 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated
|
Intralipid (Historical Control)
n=49 Participants
Patients who received Intralipid between 1999 and 2006 and whose direct bilirubin was ever \>=2.0 mg/dL.
|
|---|---|---|
|
Reversal of Cholestasis, Defined as a Direct Bilirubin to <= 2.0 mg/dL.
|
11.7 Weeks
Interval 7.7 to 13.9
|
6.4 Weeks
Interval 3.1 to 9.7
|
Adverse Events
Omegaven
Serious events: 0 serious events
Other events: 7 other events
Deaths: 3 deaths
Intralipid
Serious events: 0 serious events
Other events: 17 other events
Deaths: 12 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Omegaven
n=42 participants at risk
1g/kg/day for duration of study participation for all participants
Omegaven®: 10% Omegaven® 1g/kg/day, IV (in the vein) until the patient no longer requires parenteral nutrition or until participation in the study is terminated
Please refer to NDA report that summarizes all adverse events reported to FDA
|
Intralipid
n=49 participants at risk
Soybean oil-lipid emulsion, the standard of care lipid emulsion, with fat doses ranging from 1 to 4 g/kg/d.
|
|---|---|---|
|
Investigations
Hypertriglyceridemia
|
4.8%
2/42 • Number of events 2 • Safety assessment was made from baseline (start of oil-lipid emulsion) until week 38, at which point only one fish oil-lipid emulsion subject was being followed.
Safety assessment was based on comparison of triglycerides (TG), international normalization ratio (INR), and triene-to-tetraene (T/T) ratio. Hypertriglyceridemia was defined as TG\>400 mg/dL, while INR \> 2 and T/T ratio \> 0.2 were deemed abnormally high.
|
24.5%
12/49 • Number of events 56 • Safety assessment was made from baseline (start of oil-lipid emulsion) until week 38, at which point only one fish oil-lipid emulsion subject was being followed.
Safety assessment was based on comparison of triglycerides (TG), international normalization ratio (INR), and triene-to-tetraene (T/T) ratio. Hypertriglyceridemia was defined as TG\>400 mg/dL, while INR \> 2 and T/T ratio \> 0.2 were deemed abnormally high.
|
|
Investigations
INR > 2.0
|
7.1%
3/42 • Number of events 9 • Safety assessment was made from baseline (start of oil-lipid emulsion) until week 38, at which point only one fish oil-lipid emulsion subject was being followed.
Safety assessment was based on comparison of triglycerides (TG), international normalization ratio (INR), and triene-to-tetraene (T/T) ratio. Hypertriglyceridemia was defined as TG\>400 mg/dL, while INR \> 2 and T/T ratio \> 0.2 were deemed abnormally high.
|
10.2%
5/49 • Number of events 24 • Safety assessment was made from baseline (start of oil-lipid emulsion) until week 38, at which point only one fish oil-lipid emulsion subject was being followed.
Safety assessment was based on comparison of triglycerides (TG), international normalization ratio (INR), and triene-to-tetraene (T/T) ratio. Hypertriglyceridemia was defined as TG\>400 mg/dL, while INR \> 2 and T/T ratio \> 0.2 were deemed abnormally high.
|
|
Investigations
Essential fatty acid deficiency
|
4.8%
2/42 • Number of events 3 • Safety assessment was made from baseline (start of oil-lipid emulsion) until week 38, at which point only one fish oil-lipid emulsion subject was being followed.
Safety assessment was based on comparison of triglycerides (TG), international normalization ratio (INR), and triene-to-tetraene (T/T) ratio. Hypertriglyceridemia was defined as TG\>400 mg/dL, while INR \> 2 and T/T ratio \> 0.2 were deemed abnormally high.
|
0.00%
0/49 • Safety assessment was made from baseline (start of oil-lipid emulsion) until week 38, at which point only one fish oil-lipid emulsion subject was being followed.
Safety assessment was based on comparison of triglycerides (TG), international normalization ratio (INR), and triene-to-tetraene (T/T) ratio. Hypertriglyceridemia was defined as TG\>400 mg/dL, while INR \> 2 and T/T ratio \> 0.2 were deemed abnormally high.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place