Trial Outcomes & Findings for Compassionate Use of an Intravenous Fish Oil Emulsion in the Treatment of Liver Injury in Infants (NCT NCT00738101)
NCT ID: NCT00738101
Last Updated: 2021-05-28
Results Overview
Time in days from the initiation of fish oil emulsions (initiation of study) until resolution of cholestasis as defined by serum conjugated bilirubin≤ 2 mg/dL prior to EOS (end of study).
COMPLETED
NA
293 participants
From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).
2021-05-28
Participant Flow
Recruitment to this compassionate use protocol began in September 2007. Patients were enrolled from mainly the inpatient and some from outpatient population at Texas Children's Hospital, Houston, Texas.
There was no wash-out or run-in period.
Participant milestones
| Measure |
Fish Oil Emulsion Arm
In infants who meet the eligibility criteria for Fish Oil Emulsion arm received Fish Oil Emulsion (Omegaven) after enrollment under the study.
Therapy with Fish Oil Emulsion (Omegaven) was provided at a dose of 1 gm/kg/day (by continuous infusion) and was infused intravenously through either a central or peripheral catheter in conjunction with parenteral nutrition. If previously on Intralipid, it was stopped prior to initiation of Fish Oil Emulsion.Fish oil emulsion. Treatment was given for as long as the child needed any TPN. If the infant no longer required any TPN, then the Omegaven was stopped. Omegaven was continued even after resolution of cholestasis, as long as the need for parenteral nutrition persisted.
|
|---|---|
|
Overall Study
STARTED
|
293
|
|
Overall Study
COMPLETED
|
286
|
|
Overall Study
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Fish Oil Emulsion Arm
In infants who meet the eligibility criteria for Fish Oil Emulsion arm received Fish Oil Emulsion (Omegaven) after enrollment under the study.
Therapy with Fish Oil Emulsion (Omegaven) was provided at a dose of 1 gm/kg/day (by continuous infusion) and was infused intravenously through either a central or peripheral catheter in conjunction with parenteral nutrition. If previously on Intralipid, it was stopped prior to initiation of Fish Oil Emulsion.Fish oil emulsion. Treatment was given for as long as the child needed any TPN. If the infant no longer required any TPN, then the Omegaven was stopped. Omegaven was continued even after resolution of cholestasis, as long as the need for parenteral nutrition persisted.
|
|---|---|
|
Overall Study
Physician Decision
|
5
|
|
Overall Study
Death
|
1
|
|
Overall Study
Repeat enrollment
|
1
|
Baseline Characteristics
In the missing numbers, the gestational age at birth was not known.
Baseline characteristics by cohort
| Measure |
Fish Oil Emulsion Arm
n=286 Participants
In infants who meet the eligibility criteria for Fish Oil Emulsion arm received Fish Oil Emulsion (Omegaven) after enrollment under the study.
Therapy with Fish Oil Emulsion (Omegaven) was provided at a dose of 1 gm/kg/day (by continuous infusion) and was infused intravenously through either a central or peripheral catheter in conjunction with parenteral nutrition. If previously on Intralipid, it was stopped prior to initiation of Fish Oil Emulsion.Fish oil emulsion. Treatment was given for as long as the child needed any TPN. If the infant no longer required any TPN, then the Omegaven was stopped. Omegaven was continued even after resolution of cholestasis, as long as the need for parenteral nutrition persisted.
|
|---|---|
|
Age, Categorical
<=18 years
|
286 Participants
n=286 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=286 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=286 Participants
|
|
Age, Continuous
|
78.13 Days
STANDARD_DEVIATION 129.6 • n=286 Participants
|
|
Age, Customized
Postmenstrual Age at time of initiation
|
40.3 weeks
STANDARD_DEVIATION 17.8 • n=265 Participants • In the missing numbers, the gestational age at birth was not known.
|
|
Sex: Female, Male
Female
|
98 Participants
n=286 Participants
|
|
Sex: Female, Male
Male
|
188 Participants
n=286 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
110 Participants
n=286 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
161 Participants
n=286 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
15 Participants
n=286 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=286 Participants
|
|
Race (NIH/OMB)
Asian
|
15 Participants
n=286 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=286 Participants
|
|
Race (NIH/OMB)
Black or African American
|
62 Participants
n=286 Participants
|
|
Race (NIH/OMB)
White
|
186 Participants
n=286 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=286 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
23 Participants
n=286 Participants
|
|
Region of Enrollment
United States
|
286 participants
n=286 Participants
|
|
Infants with Cholestasis
|
286 Participants
n=286 Participants
|
|
Need for Parenteral Nutrition
|
286 Participants
n=286 Participants
|
|
Gestational Age at Birth
|
29.71 weeks
STANDARD_DEVIATION 5 • n=267 Participants • Gestational age at birth was not available in 19 infants.
|
|
Birth weight
|
1429.7 grams
STANDARD_DEVIATION 905.4 • n=225 Participants • Birth weight was not available in 61 infants
|
PRIMARY outcome
Timeframe: From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).Population: 210 out of 286 infants in the study demonstrated resolution of cholestasis prior to the end of study.
Time in days from the initiation of fish oil emulsions (initiation of study) until resolution of cholestasis as defined by serum conjugated bilirubin≤ 2 mg/dL prior to EOS (end of study).
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=210 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
|
|---|---|
|
Time to Resolution of Parenteral Nutrition Associated Cholestasis Prior to End of Study
|
38.02 Days
Standard Deviation 23.9
|
PRIMARY outcome
Timeframe: From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).To describe proportion of infants who died secondary to any cause, related or unrelated to Fish Oil Emulsion.
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=286 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
|
|---|---|
|
All Cause Mortality During the Study.
|
30 Participants
|
PRIMARY outcome
Timeframe: From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).Population: Out of 286 infants enrolled in the study, weight at the end of study was available only in 260 infants. Missing data: 26 infants.
The Z-score indicated the number of standard deviations away from the mean. A weight Z-score of 0 is equal to the mean. A weight Z-score of ≤ -2 indicates an underweight status, while a weight Z-score of ≥ 2 indicates overweight or obese status.
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=260 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
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|---|---|
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Growth Z-scores for Weight
|
-1.48 z-score
Standard Deviation 1.45
|
SECONDARY outcome
Timeframe: From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).Population: Only 285 out of 286 infants were included in this analysis. One infant had conjugated bilirubin \<2 mg/dL at the initiation of fish oil emulsion. This infant had been initiated on fish oil emulsion at another institute. Fish oil emulsion in this infant was provided as a continuation of care from another hospital.
To describe the number of infants who achieved resolution of cholestasis following initiation of fish oil emulsion.
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=285 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
|
|---|---|
|
Number of Infants Who Achieve Resolution of Parenteral Nutrition Associated Cholestasis
Resolution of Cholestasis
|
210 Participants
|
|
Number of Infants Who Achieve Resolution of Parenteral Nutrition Associated Cholestasis
Unresolved Cholestasis
|
75 Participants
|
SECONDARY outcome
Timeframe: From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).Population: Out of 286 infants enrolled in the study, weight at the end of study was available only in 264 infants. Missing data: 22 infants.
To describe the number of study subjects who experienced a platelet count below \<100,000/µL anytime during the duration of the study.
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=264 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
|
|---|---|
|
Number of Subjects With Platelet Count <100,000/µL
Platelet count <100.000/uL
|
124 Participants
|
|
Number of Subjects With Platelet Count <100,000/µL
Platelet count >100,000uL
|
140 Participants
|
SECONDARY outcome
Timeframe: From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).Population: Out of 286 infants enrolled in the study, weight at the end of study was available only in 248 infants. Missing data: 38 infants.
To describe the number of study subjects who experienced an INR ≥1.4 anytime during the duration of the study.
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=248 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
|
|---|---|
|
Number of Subjects With INR ≥1.4.
INR ≥ 1.4
|
75 Participants
|
|
Number of Subjects With INR ≥1.4.
INR ≤ 1.4
|
173 Participants
|
SECONDARY outcome
Timeframe: From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).Population: Out of 286 infants enrolled in the study, weight at the end of study was available only in 283 infants. Missing data: 3 infants.
To describe the number of study subjects who experienced a bloodstream infection during the duration of the study. Bloodstream infection as defined by detection by the culture of bacteria or fungus from the blood.
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=283 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
|
|---|---|
|
Number of Study Subjects Who Experienced a Blood Stream Infection
Blood stream infection
|
88 Participants
|
|
Number of Study Subjects Who Experienced a Blood Stream Infection
No BSI
|
195 Participants
|
SECONDARY outcome
Timeframe: From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).To describe the number and percentage of infants who required liver or multi-visceral transplant.
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=286 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
|
|---|---|
|
Liver or Multi-visceral Transplant
|
2 Participants
|
SECONDARY outcome
Timeframe: Anytime from initiation of study to discharge from the hospital.To describe number and percentage of infants who died secondary to any cause, related or unrelated to Fish Oil Emulsion.
Outcome measures
| Measure |
Fish Oil Emulsion Arm
n=286 Participants
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
|
|---|---|
|
All-cause Mortality up to Hospital Discharge
|
40 Participants
|
Adverse Events
Fish Oil Emulsion Arm
Serious adverse events
| Measure |
Fish Oil Emulsion Arm
n=286 participants at risk
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
Any cause mortality prior to the End of Study
|
|---|---|
|
Infections and infestations
Blood Stream Infection
|
30.8%
88/286 • From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).
|
Other adverse events
| Measure |
Fish Oil Emulsion Arm
n=286 participants at risk
Once eligible, Soybean Oil Emulsion was discontinued and Fish Oil Emulsion was commenced at 1 g/kg/d. Fish Oil Emulsion was provided as an infusion over 18-24 hours a day. Fish Oil Emulsion was provided in a dedicated peripheral or central venous access.
Any cause mortality prior to the End of Study
|
|---|---|
|
Hepatobiliary disorders
GGT>200 U/L
|
51.0%
146/286 • From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).
|
|
Blood and lymphatic system disorders
INR ≥ 1.4
|
26.2%
75/286 • From initiation to end of study (End of Study : Discontinuation of Fish Oil Emulsion, Death, Transplant, or Discharge from the hospital, whichever is achieved first, up to 5 years).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place