Parenteral Lipid Emulsions and the Liver Function

Four Parenteral Lipid Emulsions and the Liver Function

The randomized, double-blind, multi-centric study performed in four parallel groups to compare all lipid emulsions, which can be used as a part of PN. Patients with home parenteral nutrition due to stable intestinal failure, were randomly assigned to receive parenteral nutrition with one the following lipid emulsions:

• Long-chained triglycerides (LCT group)
• Medium/ long-chained triglycerides MCT/LCT (50:50, MCT/LCT group))
• Olive oil/ LCT (80:20, OO group))
• SMOFlipid (Omega-3/ olive oil/ MCT/ LCT, SMOF group)

Study Overview

• Status: Completed
• Conditions: Liver Failure
• Intervention / Treatment: Drug: Lipid Emulsions, Intravenous

Detailed Description

Intravenous lipid emulsion (IVLE) is the essential component of parenteral nutrition (PN), because it is a very efficient source of energy and essential fatty acids (FA).The prevalence of abnormal liver function tests during PN varies from 15 to 85%, according to most authors.[19-21] The severity of IFALD depends also on underlying disease, especially ongoing sepsis and pre-existing liver disease. A study comparing all lipid emulsions, which can be used as a part of PN, has never been done. The aim of the study was to compare the clinical value of the four most popular intravenous lipid emulsions in regards to the liver function in long term intestinal failure patients.Patients with home parenteral nutrition due to stable intestinal failure, were randomly assigned to receive parenteral nutrition with one the following lipid emulsions:

• Long-chained triglycerides (LCT group)
• Medium/ long-chained triglycerides MCT/LCT (50:50, MCT/LCT group))
• Olive oil/ LCT (80:20, OO group))
• SMOFlipid (Omega-3/ olive oil/ MCT/ LCT, SMOF group) Randomization was performed after assessment and check for in-/exclusion criteria if the patient has met all study eligibility requirements.

The test emulsion became a part of regular PN admixture, which was used to feed patient at home. The study was performed for 12 months.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 4

Contacts and Locations

Study Locations

• Poland
  • Skawina, Poland, 32-050
    • Stanley Dudrick's Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. chronic intestinal failure (CIF) receiving HPN including lipids
2. metabolic stability on HPN for more than three months (metabolic stability = the absence of pathological laboratory resulting in the change of PN regime for at least one month)
3. 1.0 g lipids/kg body weight per day as a part of PN

Exclusion Criteria:

1. Existing liver failure: an elevation of SGOT, SGTP, total bilirubin, GGTP, alkaline phosphatase of more than 1.5 times x normal value
2. Patients in whom PN was interrupted for longer than 4 continuous weeks in the preceding 6 months
3. Patients with history of cancer and anti-cancer treatment within the last 5 years
4. Severe hyperlipidemia
5. Severe coagulopathy
6. Severe renal insufficiency
7. Acute thromboembolic events
8. Positive test for HIV, Hepatitis B or C (from medical history)
9. Known or suspected drug or alcohol abuse
10. Participation in another interventional clinical trial in parallel or within three months prior to the start of this clinical trial
11. For women with childbearing potential (i.e. females who are not chemically or surgically sterile or females who are not postmenopausal) or women of childbearing potential tested positive on standard pregnancy test (urine dipstick) or/ and lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Provision of LCT emulsions in PN; Intervention: Lipid Emulsions, Intravenous. Daily provision of LCT-based lipid emulsion as a part of parenteral nutrition along with dextrose, amino acids, electrolytes, trace elements, vitamins and water in the dose of 0.8-1.0 g/kg/day.	Drug: Lipid Emulsions, Intravenous; The every day provision of lipid emulsion as a part of parenteral nutrition along with dextrose, amino acids, electrolytes, trace elements, vitamins and water in the dose of 0.8-1.0 g/kg/day.; Other Names: parenteral lipid provision
Experimental: Provision of MCT/LCT emulsions in PN; Intervention: Lipid Emulsions, Intravenous. Daily provision of MCT/LCT lipid emulsion as a part of parenteral nutrition along with dextrose, amino acids, electrolytes, trace elements, vitamins and water in the dose of 0.8-1.0 g/kg/day.	Drug: Lipid Emulsions, Intravenous; The every day provision of lipid emulsion as a part of parenteral nutrition along with dextrose, amino acids, electrolytes, trace elements, vitamins and water in the dose of 0.8-1.0 g/kg/day.; Other Names: parenteral lipid provision
Experimental: Provision of Olive oil emulsions in PN; Intervention: Lipid Emulsions, Intravenous. Daily provision of Olive-oil/ LCT lipid emulsion as a part of parenteral nutrition along with dextrose, amino acids, electrolytes, trace elements, vitamins and water in the dose of 0.8-1.0 g/kg/day.	Drug: Lipid Emulsions, Intravenous; The every day provision of lipid emulsion as a part of parenteral nutrition along with dextrose, amino acids, electrolytes, trace elements, vitamins and water in the dose of 0.8-1.0 g/kg/day.; Other Names: parenteral lipid provision
Experimental: Provision of SMOF lipid emulsions in PN; Intervention: Lipid Emulsions, Intravenous. Daily provision of SMOF lipid emulsion as a part of parenteral nutrition along with dextrose, amino acids, electrolytes, trace elements, vitamins and water in the dose of 0.8-1.0 g/kg/day.	Drug: Lipid Emulsions, Intravenous; The every day provision of lipid emulsion as a part of parenteral nutrition along with dextrose, amino acids, electrolytes, trace elements, vitamins and water in the dose of 0.8-1.0 g/kg/day.; Other Names: parenteral lipid provision

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver function	Measurement of bilirubin - at the beginning and every three months up to 12 months	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver function 2	Measurement of SGTP - at the beginning and every three months up to 12 months	12 months
Liver function 3	Measurement of SGOT - at the beginning and every three months up to 12 months	12 months
Liver function 4	Measurement of GGTP - at the beginning and every three months up to 12 months	12 months
Liver function 5	Measurement of alkaline phosphatase - at the beginning and every three months up to 12 months	12 months

Collaborators and Investigators

• Sponsor: Stanley Dudrick's Memorial Hospital
• Investigators: Principal Investigator: Stanislaw Klek, MD PhD, Stanley Dudrick's Memorial Hospital

Publications and helpful links

General Publications

• Calder PC. Hot topics in parenteral nutrition. Rationale for using new lipid emulsions in parenteral nutrition and a review of the trials performed in adults. Proc Nutr Soc. 2009 Aug;68(3):252-60. doi: 10.1017/S0029665109001268. Epub 2009 May 11. Erratum In: Proc Nutr Soc. 2011 May;70(2):281.
• Calder PC, Jensen GL, Koletzko BV, Singer P, Wanten GJ. Lipid emulsions in parenteral nutrition of intensive care patients: current thinking and future directions. Intensive Care Med. 2010 May;36(5):735-49. doi: 10.1007/s00134-009-1744-5. Epub 2010 Jan 14.
• Klek S, Szczepanek K, Scislo L, Walewska E, Pietka M, Pisarska M, Pedziwiatr M. Intravenous lipid emulsions and liver function in adult chronic intestinal failure patients: results from a randomized clinical trial. Nutrition. 2018 Nov;55-56:45-50. doi: 10.1016/j.nut.2018.03.008. Epub 2018 Mar 22.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2010
• Primary Completion (Actual): October 31, 2016
• Study Completion (Actual): December 31, 2016

Study Registration Dates

• First Submitted: January 22, 2017
• First Submitted That Met QC Criteria: February 2, 2017
• First Posted (Estimate): February 7, 2017

Study Record Updates

• Last Update Posted (Estimate): February 7, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Hepatic Insufficiency; Liver Diseases; Liver Failure; Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous
• Other Study ID Numbers: IVLE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No