PK and Safety of Caffeine in Neonates With Hypoxic Ischemic Encephalopathy Receiving Therapeutic Hypothermia

NCT05295784 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 260845
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

A phase 1 study investigating the tolerability and pharmacokinetics of caffeine citrate in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia. This study is an essential first step to develop caffeine as a kidney protective medication in this in this vulnerable group of newborns.

Conditions

Acute Kidney Injury; Hypoxic-Ischemic Encephalopathy; Caffeine

Outcome Measures

Primary Outcomes (6)

• Clearance of caffeine

  Clearance (mL h-1 kg-1)

  1 week

• Volume of distribution of caffeine

  Volume of distribution (ml/kg)

  1 week

• Peak plasma concentration (Cmax) of caffeine

  Peak plasma concentration (Cmax) (ng/mL)

  1 week

• Area under the plasma concentration-time curve of caffeine

  Area under the plasma concentration-time curve from 0 to infinity (AUC0-INF) (mg\*h/L)

  1 week

• Seizure incidence

  Number of neonates who developed seizures based on continuous video electroencephalogram (VEEG) data

  2 weeks

• Seizure burden

  Electrographic seizures (in minutes per hour) based on continuous video electroencephalogram (VEEG) data

  2 weeks

Secondary Outcomes (5)

• Acute kidney injury

  10 days

• Renal near infrared spectroscopy (NIRS)

  5 days

• Urine neutrophil gelatinase-associated lipocalin (NGAL) (ng/mL)

  3 days

• Urine kidney injury molecule-1 (KIM-1) (pg/mL)

  3 days

• Urine interleukin-18 (IL-18) (pg/mL)

  3 days

Study Arms (3)

Arm 1: Low dose caffeine

ACTIVE COMPARATOR

Each neonate will receive a single dose of caffeine citrate in the first 24 hours of life. Arm 1 neonates will receive low dose intravenous caffeine citrate (5 mg/kg).

Drug: Caffeine citrate

Arm 2: Medium dose caffeine

ACTIVE COMPARATOR

Each neonate will receive a single dose of caffeine citrate in the first 24 hours of life. Arm 2 neonates will receive medium dose intravenous caffeine citrate (15 mg/kg).

Drug: Caffeine citrate

Arm 3: High dose caffeine

ACTIVE COMPARATOR

Each neonate will receive a single dose of caffeine citrate in the first 24 hours of life. Arm 3 neonates will receive high dose intravenous caffeine citrate (25 mg/kg).

Drug: Caffeine citrate

Interventions

Caffeine citrate DRUG

A single dose of intravenous caffeine citrate will be administered to neonates with hypoxic ischemic encephalopathy to determine the pharmacokinetics and tolerability.

Also known as: Cafcit

Arm 1: Low dose caffeine; Arm 2: Medium dose caffeine; Arm 3: High dose caffeine

Eligibility Criteria

• Age: 0 Hours - 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Newborns ≥ 35 weeks GA
• Admitted to the ACH NICU less than 24 hours of life
• Receiving active or passive TH or whole-body cooling at 12 hours of life to treat hypoxic ischemic encephalopathy per institutional criteria based on National Institute of Child Health and Human Development criteria

You may not qualify if:

• Genetic or congenital condition that affects renal function (e.g., congenital anomalies of the kidney and urinary tract (CAKUT), complex congenital heart disease)
• Diminished capacity or autonomy of the neonate's parents that prevents their ability to give informed consent
• Theophylline, aminophylline, or caffeine exposure prior to enrollment
• Status epilepticus as defined by:
• A seizure lasting longer than 30 minutes
• Use of a continuous infusion of antiepileptic medication (i.e., midazolam)
• The use of 3 or more antiepileptic medications for the indications of intractable seizures

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (2)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (33)

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MeSH Terms

Conditions

Acute Kidney Injury; Hypoxia-Ischemia, Brain

Interventions

caffeine citrate

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jennifer Rumpel, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each neonate will receive a single dose of caffeine citrate in the first 24 hours of life. The first six neonates will receive low dose (5 mg/kg), the next six neonates will receive a medium dose (15 mg/kg), and the next six neonates will receive high dose or (25 mg/kg).

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 25, 2022
• Study Start: May 8, 2024
• Primary Completion: May 8, 2024
• Study Completion: May 8, 2024
• Last Updated: May 10, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)