Bilirubin Neurotoxicity (BN) and Neurodevelopmental Impairment (NDI) in Extremely Preterm (EP) Infants: Avoidable by Reducing the Usual Intravenous Lipid (UL) Administration

NCT04584983 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: HSC-MS-20-0916KL2TR003168
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of usual versus reduced lipid intake on unbound bilirubin levels, brainstem auditory evoked responses, and neurodevelopmental outcome at 2 years in extremely preterm infants.

Conditions

Bilirubin Encephalopathy

Keywords

preterm; bilirubin; lipid emulsions; unbound bilirubin; unbound free fatty acids

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Unbound Bilirubin (UB) Concentration Greater Than 30 Nanomoles Per Liter (Nmol/L)

  within first 14 days of life

• Average Unbound Bilirubin (UB) Concentration

  6 UB measurements will be taken per participant .Average of the 6 readings will be reported

  within first 14 days of life

• Brain Stem Auditory-evoked Response (BAER) V Latency

  Brainstem auditory evoked response (BAER) testing is a procedure used to assess the auditory pathways of the brainstem and evaluate hearing ability. Wave latency, measured in milliseconds, is the measure of electric transmission of sound. If the wave latency is prolonged, this means that something is in the way of electric sound wave transmission, such as bilirubin which has an affinity for depositing in a specific area of the brainstem that wave V measures.

  38 weeks post menstrual age(PMA)

Secondary Outcomes (19)

• Peak Free Fatty Acid Uptake (FFAU)

  within first 14 days of life

• Peak UB Concentration

  within first 14 days of life

• Total Unbound Free Fatty Acids (FFA)

  within first 14 days of life

• Peak Total Serum Bilirubin

  within first 14 days of life

• Number of Patients With Direct Bilirubin Greater Than 1.5 mg/dL

  Before discharge (discharge is on average 3 months after birth)

Study Arms (2)

usual prescribed intralipid (UL) regimen

ACTIVE COMPARATOR

Drug: usual prescribed intralipid (UL) regimen

restricted prescribed intralipid (RL) regimen

EXPERIMENTAL

Drug: restricted prescribed intralipid (RL) regimen

Interventions

usual prescribed intralipid (UL) regimen DRUG

Intralipid will be started at 1 g/kg/day and routinely advanced by 1 g/kg/day each day to a max of 3 g/kg/day as per usual clinical practice

usual prescribed intralipid (UL) regimen

restricted prescribed intralipid (RL) regimen DRUG

Intralipid will be started at 0.5 g/kg/day and routinely advanced by 0.5 g/kg/day each day to a max of 1.5 g/kg/day (half rate of usual clinical practice).

restricted prescribed intralipid (RL) regimen

Eligibility Criteria

• Age: Up to 27 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• no major congenital anomaly or overt nonbacterial infection

You may not qualify if:

• has received Intralipid

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Holzapfel LF, Arnold C, Tyson JE, Shapiro SM, Reynolds EW, Pedroza C, Stephens EK, Kleinfeld A, Huber AH, Rysavy MA, Del Mar Romero Lopez M, Khan AM. Effect of reduced versus usual lipid emulsion dosing on bilirubin neurotoxicity and neurodevelopmental impairment in extremely preterm infants: study protocol for a randomized controlled trial. BMC Pediatr. 2023 Jul 10;23(1):347. doi: 10.1186/s12887-023-04149-0.

  PMID: 37430233 BACKGROUND

• Holzapfel L, Arnold C, Tyson J, Shapiro S, Reynolds E, Pedroza C, Stephens E, Kleinfeld A, Huber A, Rysavy M, Khan A, Del Mar Romero Lopez M. Effect of Reduced Versus Usual Lipid Emulsion Dosing on Bilirubin Neurotoxicity and Neurodevelopmental Impairment in Extremely Preterm Infants: Study Protocol for a Randomized Controlled Trial. Res Sq [Preprint]. 2023 Mar 7:rs.3.rs-2566352. doi: 10.21203/rs.3.rs-2566352/v1.

  PMID: 36945475 DERIVED

MeSH Terms

Conditions

Kernicterus; Premature Birth

Interventions

Clinical Protocols

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Erythroblastosis, Fetal; Hematologic Diseases; Hemic and Lymphatic Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Immune System Diseases; Hyperbilirubinemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Lindsay F Holzapfel, MD, MS
• Organization: The University of Texas Health Science Center at Houston

Lindsay.N.Fleig@uth.tmc.edu

713-500-6422

Study Officials

• Lindsay F Holzapfel, MD, MS

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 14, 2020
• Study Start: February 11, 2021
• Primary Completion: March 14, 2024
• Study Completion (Estimated): June 14, 2026
• Last Updated: November 28, 2025
• Results First Posted: November 28, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)