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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01FD003460-02 | U.S. FDA Grant/Contract | View source |
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The purpose of this study is to determine whether Omegaven is effective in the treatment of parenteral nutrition associated liver disease (PNALD).
The purpose of this study is to determine whether the omega-3 fatty acid emulsion (Omegaven), when used in lieu of the conventional soy-based fat emulsion (Intralipid), is effective in the treatment of parenteral nutrition associated liver disease (PNALD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Omegaven | Experimental | 1g/kg/day for duration of study participation for all participants |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Omegaven® | Drug | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Reversal of Cholestasis, Defined as a Direct Bilirubin to <= 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. | Duration of treatment |
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Inclusion Criteria:
Exclusion Criteria:
In rare instances, patients diagnosed with PNALD may later be found to have liver disease due to other causes in addition to the use of PN (i.e., inborn errors of metabolism, viral infections ). Such causes may not be known at the time of enrollment and will not preclude them from continuing in the study. For the sake of statistical analysis, however, these patients will be excluded although all data will be collected and reviewed.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Boston | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18310188 | Background | Gura KM, Lee S, Valim C, Zhou J, Kim S, Modi BP, Arsenault DA, Strijbosch RA, Lopes S, Duggan C, Puder M. Safety and efficacy of a fish-oil-based fat emulsion in the treatment of parenteral nutrition-associated liver disease. Pediatrics. 2008 Mar;121(3):e678-86. doi: 10.1542/peds.2007-2248. | |
| 16818533 | Background | Gura KM, Duggan CP, Collier SB, Jennings RW, Folkman J, Bistrian BR, Puder M. Reversal of parenteral nutrition-associated liver disease in two infants with short bowel syndrome using parenteral fish oil: implications for future management. Pediatrics. 2006 Jul;118(1):e197-201. doi: 10.1542/peds.2005-2662. |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Intralipid | Intralipid®: 20% Intralipid® up to 3g/kg/day, IV (in the vein). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Includes subjects treated with Omegaven and subjects who served as historical controls treated with Intralipid. Four participants who were transferred to Boston Children's after starting Omegaven at another institution do not have a baseline direct bilirubin (DB). These same four subjects plus two subjects on Intralipid do not have a PN start date, so duration of PN will be unknown in these cases. Therefore, the sample size for DB will be 38+49=87 and for duration of PN 38+47=85.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Intralipid (Historical Control) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Reversal of Cholestasis, Defined as a Direct Bilirubin to <= 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. | The primary efficacy end-point was time to reversal of cholestasis (direct bilirubin <= 2.0 mg/dL). | Posted | Median | Inter-Quartile Range | Weeks | Duration of treatment |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 Please refer to NDA report that summarizes all adverse events reported to FDA |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertriglyceridemia | Investigations | Non-systematic Assessment | Triglycerides > 400 mg/dL |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark Puder MD PhD | Boston Children's Hospital | 617-355-1838 | mark.puder@childrens.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 29, 2021 | Dec 6, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012778 | Short Bowel Syndrome |
| D005767 | Gastrointestinal Diseases |
| D002779 | Cholestasis |
| ID | Term |
|---|---|
| D008286 | Malabsorption Syndromes |
| D007410 | Intestinal Diseases |
| D004066 | Digestive System Diseases |
| D011183 | Postoperative Complications |
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| ID | Term |
|---|---|
| C568345 | fish oil triglycerides |
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| 27979360 | Background | Nandivada P, Anez-Bustillos L, O'Loughlin AA, Mitchell PD, Baker MA, Dao DT, Fell GL, Potemkin AK, Gura KM, Neufeld EJ, Puder M. Risk of post-procedural bleeding in children on intravenous fish oil. Am J Surg. 2017 Oct;214(4):733-737. doi: 10.1016/j.amjsurg.2016.10.026. Epub 2016 Dec 1. |
| 27510535 | Background | Nandivada P, Baker MA, Mitchell PD, O'Loughlin AA, Potemkin AK, Anez-Bustillos L, Carlson SJ, Dao DT, Fell GL, Gura KM, Puder M. Predictors of failure of fish-oil therapy for intestinal failure-associated liver disease in children. Am J Clin Nutr. 2016 Sep;104(3):663-70. doi: 10.3945/ajcn.116.137083. Epub 2016 Aug 10. |
| 26962059 | Background | Nandivada P, Fell GL, Mitchell PD, Potemkin AK, O'Loughlin AA, Gura KM, Puder M. Long-Term Fish Oil Lipid Emulsion Use in Children With Intestinal Failure-Associated Liver Disease [Formula: see text]. JPEN J Parenter Enteral Nutr. 2017 Aug;41(6):930-937. doi: 10.1177/0148607116633796. Epub 2016 Mar 9. |
| 24374535 | Background | Nandivada P, Chang MI, Potemkin AK, Carlson SJ, Cowan E, O'loughlin AA, Mitchell PD, Gura KM, Puder M. The natural history of cirrhosis from parenteral nutrition-associated liver disease after resolution of cholestasis with parenteral fish oil therapy. Ann Surg. 2015 Jan;261(1):172-9. doi: 10.1097/SLA.0000000000000445. |
| 21775562 | Background | Le HD, de Meijer VE, Robinson EM, Zurakowski D, Potemkin AK, Arsenault DA, Fallon EM, Malkan A, Bistrian BR, Gura KM, Puder M. Parenteral fish-oil-based lipid emulsion improves fatty acid profiles and lipids in parenteral nutrition-dependent children. Am J Clin Nutr. 2011 Sep;94(3):749-58. doi: 10.3945/ajcn.110.008557. Epub 2011 Jul 20. |
| 19661785 | Result | Puder M, Valim C, Meisel JA, Le HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM. Parenteral fish oil improves outcomes in patients with parenteral nutrition-associated liver injury. Ann Surg. 2009 Sep;250(3):395-402. doi: 10.1097/SLA.0b013e3181b36657. |
| 34695449 | Derived | Gura KM, Calkins KL, Premkumar MH, Puder M. Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events. J Pediatr. 2022 Feb;241:173-180.e1. doi: 10.1016/j.jpeds.2021.10.030. Epub 2021 Oct 23. |
| 33038344 | Derived | Gura KM, Premkumar MH, Calkins KL, Puder M. Fish Oil Emulsion Reduces Liver Injury and Liver Transplantation in Children with Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Study. J Pediatr. 2021 Mar;230:46-54.e2. doi: 10.1016/j.jpeds.2020.09.068. Epub 2020 Oct 8. |
| 32059815 | Derived | Gura K, Premkumar MH, Calkins KL, Puder M. Intravenous Fish Oil Monotherapy as a Source of Calories and Fatty Acids Promotes Age-Appropriate Growth in Pediatric Patients with Intestinal Failure-Associated Liver Disease. J Pediatr. 2020 Apr;219:98-105.e4. doi: 10.1016/j.jpeds.2019.12.065. Epub 2020 Feb 12. |
Patients who received Intralipid between 1999-2006 and whose direct bilirubin was ever >=2.0 mg/dL. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Race and ethnicity not reliably obtained on all subjects. | Count of Participants | Participants |
|
| Direct bilirubin | Patients who were transferred to Boston Children's after starting Omegaven elsewhere do not have a baseline direct bilirubin available. | Median | Inter-Quartile Range | mg/dL |
|
| Duration of PN before enrollment (d), median (IQR) | PN start date is unknown for n=4 in the fish oil-emulsion arm and n=2 in the soybean oil-emulsion arm. | Median | Inter-Quartile Range | Days |
|
Patients who received Intralipid between 1999 and 2006 and whose direct bilirubin was ever >=2.0 mg/dL.
|
|
|
| 3 |
| 42 |
| 0 |
| 42 |
| 7 |
| 42 |
| EG001 | Intralipid | Soybean oil-lipid emulsion, the standard of care lipid emulsion, with fat doses ranging from 1 to 4 g/kg/d. | 12 | 49 | 0 | 49 | 17 | 49 |
|
| INR > 2.0 | Investigations | Non-systematic Assessment | International normalized ratio > 2.0 |
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| Essential fatty acid deficiency | Investigations | Non-systematic Assessment | Triene:tetraene ratio > 0.2 |
|
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| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001649 | Bile Duct Diseases |
| D001660 | Biliary Tract Diseases |
| Unknown or Not Reported |
|