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

• ClinicalTrials.gov Identifier: NCT04555044
• Recruitment Status: Recruiting
• First Posted: September 18, 2020
• Last Update Posted: January 11, 2022
• Sponsor: Baxter Healthcare Corporation
• Information provided by (Responsible Party): Baxter Healthcare Corporation

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Essential Fatty Acid Deficiency (EFAD)	Drug: Clinolipid; Drug: Intralipid	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: January 22, 2021
• Estimated Primary Completion Date: July 30, 2023
• Estimated Study Completion Date: July 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Clinolipid; 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: Clinolipid; Lipid injectable emulsion, USP 20%
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)

Outcome Measures

Primary Outcome Measures :

1. Number of participants to develop Essential Fatty Acid Deficiency (EFAD) [ Time Frame: Up to Day 90 ]
   Determined by Holman Index value >0.4

Secondary Outcome Measures :

1. Number of participants to develop Parenteral Nutrition-Associated Liver Disease (PNALD) [ Time Frame: Up to Day 90 ]
   Defined by direct bilirubin ≥2 mg/dL when no other etiology for liver dysfunction is present in patients receiving with intravenous lipid emulsion (ILE).
2. Body Weight [ Time Frame: Up to Day 90 ]
   Gain in weight (g/kg/day in infants <1 year of age, g/day in children and adolescents).
3. Stigmasterol Blood Level [ Time Frame: Up to Day 90 ]
   Phytosterol species.
4. Campesterol Blood Level [ Time Frame: Up to Day 90 ]
   Phytosterol species.
5. Sitosterol Blood Level [ Time Frame: Up to Day 90 ]
   Phytosterol species.
6. Cholesterol Blood Level [ Time Frame: Up to Day 90 ]
7. Squalene Blood Level [ Time Frame: Up to Day 90 ]
8. Alkaline Phosphatase (ALP) [ Time Frame: Up to Day 90 ]
   Hepatic Integrity will be assessed by measuring plasma liver function tests.
9. Aspartate Aminotransferase (AST) [ Time Frame: Up to Day 90 ]
   Hepatic Integrity will be assessed by measuring plasma liver function tests.
10. Alanine Aminotransferase (ALT) [ Time Frame: Up to Day 90 ]
    Hepatic Integrity will be assessed by measuring plasma liver function tests.
11. Gamma-Glutamyl Transferase (GGT), [ Time Frame: Up to Day 90 ]
    Hepatic Integrity will be assessed by measuring plasma liver function tests.
12. Total Bilirubin [ Time Frame: Up to Day 90 ]
    Hepatic Integrity will be assessed by measuring plasma liver function tests.
13. Direct Bilirubin [ Time Frame: Up to Day 90 ]
    Will be assessed by measuring plasma liver function tests: alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and total and direct bilirubin.
14. Calories nutritional intake [ Time Frame: Up to Day 90 ]
    Intravenous intakes from parenteral nutrition (PN) as well as any intravenous macronutrient additions to the PN solution will be collected and recorded as parenteral intakes. Also enteral/oral nutrition will be collected. For breast milk intake, the macronutrient content will be estimated from volume intakes using mean reference values in mature human milk. Prescribed and actual nutritional intakes.
15. Protein nutritional intake [ Time Frame: Up to Day 90 ]
    Intravenous intakes from parenteral nutrition (PN) as well as any intravenous macronutrient additions to the PN solution will be collected and recorded as parenteral intakes. Also enteral/oral nutrition will be collected. For breast milk intake, the macronutrient content will be estimated from volume intakes using mean reference values in mature human milk. Prescribed and actual nutritional intakes.
16. Lipids nutritional intake [ Time Frame: Up to Day 90 ]
    Intravenous intakes from parenteral nutrition (PN) as well as any intravenous macronutrient additions to the PN solution will be collected and recorded as parenteral intakes. Also enteral/oral nutrition will be collected. For breast milk intake, the macronutrient content will be estimated from volume intakes using mean reference values in mature human milk. Prescribed and actual nutritional intakes.
17. Carbohydrates nutritional intake [ Time Frame: Up to Day 90 ]
    Intravenous intakes from parenteral nutrition (PN) as well as any intravenous macronutrient additions to the PN solution will be collected and recorded as parenteral intakes. Also enteral/oral nutrition will be collected. For breast milk intake, the macronutrient content will be estimated from volume intakes using mean reference values in mature human milk. Prescribed and actual nutritional intakes
18. Adverse Events (AE) Rate per 100 patient days [ Time Frame: Up to Day 120 (30 Days After Subject's Last Study Treatment if hospital discharge has not occurred) ]
    The AE rate per 100 patient days will be reported for the overall study period, and may be stratified into Weeks 1, 2, 3, and 4 as appropriate.
19. Length or height (and head circumference for infants <1 year of age) [ Time Frame: Up to Day 90 ]
    Gain in length/height (mm/week in all) and head circumference (mm/week in infants <1 year).
20. Number of Participants with Neonatal morbidities [ Time Frame: Up to Day 90 ]
    Includes bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), and late-onset sepsis in enrolled premature infants born <37 weeks of gestation.
21. Adverse Event's of Special Interest [ Time Frame: Up to Day 120 (30 Days After Subject's Last Study Treatment if hospital discharge has not occurred) ]
    Will include known AE's related to parenteral nutrition (PN) with intravenous lipid emulsion (ILE).

Eligibility Criteria

• Ages Eligible for Study: up to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 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 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.

Contacts and Locations

Contacts

Contact: Baxter Clinical Trials Disclosure Call Center; (224) 948-7359; Global_CORP_ClinicalTrialsDisclosure@baxter.com

Locations

United States, Alabama

Baxter Investigational Site; Recruiting

Mobile, Alabama, United States, 36604

United States, California

Baxter Investigational Site; Not yet recruiting

Orange, California, United States, 92868

United States, Connecticut

Baxter Investigational Site; Not yet recruiting

New Haven, Connecticut, United States, 06511

United States, Florida

Baxter Investigational Site; Not yet recruiting

Miami, Florida, United States, 33136

Baxter Investigational Site; Recruiting

Orlando, Florida, United States, 32803

United States, Illinois

Baxter Investigational Site; Not yet recruiting

Chicago, Illinois, United States, 60153

United States, Massachusetts

Baxter Investigational Site; Not yet recruiting

Boston, Massachusetts, United States, 02111

United States, Mississippi

Baxter Investigational Site; Recruiting

Jackson, Mississippi, United States, 39157

United States, New Jersey

Baxter Investigational Site; Not yet recruiting

Jersey City, New Jersey, United States, 07302

United States, North Carolina

Baxter Investigational Site; Recruiting

Greenville, North Carolina, United States, 27834

United States, Tennessee

Baxter Investigational Site; Recruiting

Memphis, Tennessee, United States, 38163

United States, Texas

Baxter Investigational Site; Recruiting

San Antonio, Texas, United States, 78229

United States, Utah

Baxter Investigational Site; Recruiting

Provo, Utah, United States, 84604

Sponsors and Collaborators

Baxter Healthcare Corporation

Investigators

• Study Director: Baxter Healthcare Corporation; Baxter Healthcare Corporation

More Information

• Responsible Party: Baxter Healthcare Corporation
• ClinicalTrials.gov Identifier: NCT04555044
• Other Study ID Numbers: 6344-001A
• First Posted: September 18, 2020
• Last Update Posted: January 11, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Baxter Healthcare Corporation:

Essential Fatty Acids (EFA); Parenteral Nutrition; Clinolipid/Clinoleic; Parenteral Nutrition Associated Cholestasis (PNAC); Parenteral Nutrition Associated Liver Disease (PNALD); Intestinal Failure Associated Liver Disease (IFALD); Phytosterols; Intralipid; Infants/Preterm Infants; FADS1 and FADS2; Short Bowel Syndrome; Cancer Nutrition; Olive Oil Emulsion; Soybean Oil Emulsion

Additional relevant MeSH terms:

Soybean oil, phospholipid emulsion; Fat Emulsions, Intravenous; Parenteral Nutrition Solutions; Pharmaceutical Solutions