Pediatric Study to Evaluate Risk of Developing Essential Fatty Acid Deficiency When Receiving Clinolipid or Standard-of-Care Lipid Emulsion (Part A)

A Randomized, Double-Blind, Controlled, Clinical Trial to Evaluate the Risk of Developing Essential Fatty Acid Deficiency in Pediatric Patients, Including Neonates, Receiving Either Clinolipid (Lipid Injectable Emulsion, USP) 20% or Standard-of-Care Soybean Oil-Based Lipid Emulsion (Part A)

This will be a descriptive study designed to evaluate the propensity for hospitalized pediatric patients treated adequately with Clinolipid or standard of care (Intralipid) from 7 up to 90 days to develop Essential Fatty Acid Deficiency (EFAD). Additionally, this study design will evaluate the safety and efficacy of using Clinolipid or Intralipid in a pediatric population.

Study Overview

• Status: Completed
• Conditions: Essential Fatty Acid Deficiency (EFAD)
• Intervention / Treatment: Drug: Clinolipid; Drug: Intralipid

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36604
      • Baxter Investigational SIte
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Baxter Investigational SIte
  • Florida
    • Orlando, Florida, United States, 32803
      • Baxter Investigational SIte
  • Massachusetts
    • Boston, Massachusetts, United States, 09111
      • Baxter Investigational SIte
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Baxter Investigational SIte
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Baxter Investigational SIte
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • Baxter Investigational SIte
  • Texas
    • San Antonio, Texas, United States, 78229
      • Baxter Investigational SIte
  • Utah
    • Provo, Utah, United States, 84604
      • Baxter Investigational SIte

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients and/or their legal representative must be able to understand the study and voluntarily sign the informed consent form (ICF) per 21 CFR Part 50.55(e)
2. Patients and/or their legal representative accept adherence to protocol requirements
3. Patients who are expected to require parenteral nutrition (PN)for at least 7 days
4. Premature infants (born at 24 to <37 weeks of gestation with a birth weight ≥750g) require at least 80% of targeted energy requirements by PN at study entry (up to 1 month CA); full term infants and children require at least 70% of targeted energy requirements by PN at study entry

Exclusion Criteria:

1. Patients who are not expected to survive hospitalization or with a severe critical unresponsive illness at time of initiation with foreseeable intercurrent events that could jeopardize the patient's participation in the study, as judged by the Investigator (e.g., unresponsive shock, sepsis, renal failure requiring dialysis, severe unresponsive metabolic acidosis, and/or severe unresponsive metabolic disorders);
2. Patients with a known hypersensitivity to lipid emulsion, egg or soybean proteins, or any of the active substances, excipients, or components of the container or who have a history of an adverse event due to ILE;
3. Patients with liver disease including cholestasis;
4. Patients with severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia (triglyceride >400 mg/dL);
5. Patients who are unable to tolerate the necessary laboratory monitoring;
6. Patients who are enrolled in another clinical trial involving an investigational agent;
7. Patients with a known history of either severe hemorrhagic or severe hemolytic disease as judged by the investigator;
8. Premature infants born <24 weeks of gestation and patients ≥18 years;
9. Premature infants with a birth weight <750 g;
10. Patient requires or is expected to require propofol for sedation;
11. Patient has received a diagnosis of Coronavirus Disease of 2019 (COVID-19) (diagnosis <2 months prior and/or symptoms have not resolved.
12. Newborn patient born to a mother who was diagnosed as COVID-19 positive at delivery or within 2 months prior to delivery
13. Female patients who are pregnant. Note: All female patients ≥12 years of age must have a negative urine human chorionic gonadotropin (hCG) pregnancy test at screening. For female patients <12 years of age, a urine hCG test at screening will be performed at the discretion of the investigator based on childbearing potential.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intralipid; Dosing based on AAP, ASPEN, ESPGHAN/ESPEN/ESPR/CSPEN guidelines. Study treatment will be administered intravenously in the hospital setting from 7 up to 90 days using either a syringe pump or an infusion pump as appropriate for the daily volume of infusate. The flow rate will be prescribed by the Investigator to provide the daily dosage over 20 to 24 hours.	Drug: Intralipid; Standard-of-Care Soybean Oil-Based Lipid Emulsion. 20% (lipid injectable emulsion, USP)
Experimental: Clinolipid; Dosing based on American Academy of Pediatrics (AAP), American Academy Society for Parenteral and Enteral Nutrition (ASPEN), European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN)/ European Society for Parenteral and Enteral Nutrition (ESPEN)/ European Society of Paediatric Research (ESPR)/ Chinese Society for Parenteral and Enteral Nutrition (CSPEN) guidelines. Study treatment will be administered intravenously in the hospital setting from 7 up to 90 days using either a syringe pump or an infusion pump as appropriate for the daily volume of infusate. The flow rate will be prescribed by the Investigator to provide the daily dosage over 20 to 24 hours.	Drug: Clinolipid; Lipid injectable emulsion, USP 20%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants to Develop Essential Fatty Acid Deficiency (EFAD) Defined by Holman Index > 0.4	Holman Index is the plasma Triene:Tetraene ratio, specifically 5,8,11-eicosatrienoic acid [mead acid] to 5,8,11,14 eicosatetraenoic acid [arachidonic acid, [ARA] ratio	Up to Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cholesterol Blood Level		Up to Day 90
Squalene Blood Level		Up to Day 90
Number of Participants to Develop Parenteral Nutrition-Associated Liver Disease (PNALD)	Defined by direct bilirubin ≥2 mg/dL in patients receiving with intravenous lipid emulsion (ILE).	Up to Day 90
Alkaline Phosphatase (ALP)	Plasma liver function test	Up to Day 90
Aspartate Aminotransferase (AST)	Plasma liver function test	Up to Day 90
Alanine Aminotransferase (ALT)	Plasma liver function test	Up to Day 90
Gamma-Glutamyl Transferase (GGT)	Plasma liver function test	Up to Day 90
Total Bilirubin	Plasma liver function test	Up to Day 90
Direct Bilirubin	Plasma liver function test	Up to Day 90
Stigmasterol Blood Level	Phytosterol species	Up to Day 90
Campesterol Blood Level	Phytosterol species	Up to Day 90
Sitosterol Blood Level	Phytosterol species.	Up to day 90
Calories Nutritional Intake		Up to Day 90
Protein Nutritional Intake		Up to Day 90
Lipid Nutritional Intake		Up to Day 90
Carbohydrates Nutritional Intake		Up to Day 90
Change in Length or Height (and Head Circumference for Infants <1 Year of Age) From Baseline	Change in length/height from baseline (mm/week in all) = [Length (mm) on Day X - Length (mm) at baseline] / [X/7] Change in head circumference from baseline (mm/week in infants <1 year) = [Head circumference (mm) on Day X - Head circumference (mm) at baseline] / [X/7]	Up to Day 90
Body Weight	Change in Weight. from baseline (g/kg/day) to EOT for infants < 1 year of Age	Up to day 90
Body Weight	Change in weight from baseline to end of treatment (EOT) for those > 1 year of age (g/day)	Upto Day 90
Number of Adverse Events of Special Interest		Up to Day 120 (30 Days After Subject's Last Study Treatment if hospital discharge has not occurred)
Number of Participants With Neonatal Morbidities	Neonatal Morbidities are presented for premature infants born < 37 weeks of gestation up to 1 month corrected age. Patients may have more than 1 neonatal morbidity.	Up to Day 90

Collaborators and Investigators

• Sponsor: Baxter Healthcare Corporation
• Investigators: Study Director: Baxter Healthcare Corporation, Baxter Healthcare Corporation

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2021
• Primary Completion (Actual): October 16, 2022
• Study Completion (Actual): November 16, 2022

Study Registration Dates

• First Submitted: September 8, 2020
• First Submitted That Met QC Criteria: September 16, 2020
• First Posted (Actual): September 18, 2020

Study Record Updates

• Last Update Posted (Actual): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 6, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Parenteral Nutrition; Intralipid; Phytosterols; Short Bowel Syndrome; Essential Fatty Acids (EFA); Clinolipid/Clinoleic; Parenteral Nutrition Associated Cholestasis (PNAC); Parenteral Nutrition Associated Liver Disease (PNALD); Intestinal Failure Associated Liver Disease (IFALD); Infants/Preterm Infants; FADS1 and FADS2; Cancer Nutrition; Olive Oil Emulsion; Soybean Oil Emulsion
• Additional Relevant MeSH Terms: Pharmaceutical Solutions; Parenteral Nutrition Solutions; Fat Emulsions, Intravenous; Soybean oil, phospholipid emulsion
• Other Study ID Numbers: 6344-001A

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: Yes
• Studies a U.S. FDA-regulated device product: No