Caffeine Citrate for Newborn Brain Injury

Recruiting at 1 trial location

Overseen By Jenny Rumpel, MD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Arkansas

Must not be taking: Theophylline, Aminophylline, Caffeine

Disqualifiers: Genetic conditions, Status epilepticus, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

Trial Summary

What is the purpose of this trial?

This trial is testing if caffeine can protect the kidneys of newborns with brain injury due to lack of oxygen at birth. These babies are at high risk for kidney problems, and current treatments are limited. Caffeine might help by improving urine output and reducing kidney damage.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications, but newborns who have been exposed to theophylline, aminophylline, or caffeine before enrollment cannot participate.

What data supports the effectiveness of the drug Caffeine Citrate for newborn brain injury?

Caffeine Citrate has been shown to significantly reduce apnea (pauses in breathing) events in preterm infants, which suggests it helps improve breathing and oxygen levels. This could indirectly support its potential effectiveness in treating newborn brain injury, as better oxygenation may protect the brain. ^{1 2 3 4 5}

Is caffeine citrate safe for use in newborns?

Caffeine citrate has been used in studies with preterm infants to treat apnea (breathing pauses), and while many participants experienced adverse events, only one non-serious event was linked to the treatment. This suggests that caffeine citrate is generally safe for use in newborns, though monitoring for side effects is important. ^{2 3 4 6 7}

How is the drug caffeine citrate unique for treating newborn brain injury?

Caffeine citrate is unique because it is primarily used for treating apnea (breathing pauses) in premature infants, and it works by stimulating the central nervous system to improve breathing. While it is not specifically designed for newborn brain injury, its use in managing apnea could indirectly benefit brain health by ensuring better oxygenation. ^{1 4 6 8 9}

Research Team

Jennifer Rumpel, MD

Principal Investigator

University of Arkansas

Eligibility Criteria

This trial is for newborns at least 35 weeks old with hypoxic ischemic encephalopathy, undergoing cooling therapy to treat brain injury caused by oxygen deprivation. Babies can't join if they have genetic conditions affecting the kidneys, severe ongoing seizures, or prior exposure to similar drugs like theophylline.

Inclusion Criteria

I am undergoing cooling treatment for brain injury due to lack of oxygen at birth.

My newborn was admitted to the NICU within 24 hours of birth and was at least 35 weeks gestational age.

Exclusion Criteria

I have a genetic condition that affects my kidney function.

I have not taken theophylline, aminophylline, or caffeine before joining.

I have had a very long seizure or needed many medicines to control my seizures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Neonates receive a single dose of caffeine citrate within the first 24 hours of life, with varying doses based on the study arm

1 day

1 visit (in-person)

Monitoring

Blood and urine samples are collected to monitor caffeine levels, kidney function, and seizure activity

2 weeks

Continuous monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on seizure incidence and kidney function

2 weeks

Treatment Details

Interventions

• Caffeine Citrate

Trial Overview The study tests how safe caffeine citrate is for these babies and how their bodies handle the drug. It's a first step in exploring whether caffeine can protect their kidneys during this critical time.

Participant Groups

Group I: Arm 2: Medium dose caffeine Active Control 1 Intervention

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).

Group II: Arm 3: High dose caffeine Active Control 1 Intervention

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).

Group III: Arm 1: Low dose caffeine Active Control 1 Intervention

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).

Who Is Running the Clinical Trial?

University of Arkansas

Lead Sponsor

Trials

500

Recruited

153,000+

Findings from Research

A study of 566 preterm infants showed that a high maintenance dose of caffeine citrate (10 mg/kg per day) significantly reduced the need for high-concentration oxygen and the duration of oxygen therapy compared to a low dose (5 mg/kg per day).

While the high-dose group experienced benefits in respiratory support and reduced incidence of apnea and bronchopulmonary dysplasia, it also had a higher rate of feeding intolerance, indicating a need for further research on this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study. Yang, Y., Lu, KY., Cheng, R., et al.[2022]

A population pharmacokinetic (PPK) model for caffeine citrate was developed using data from 46 preterm infants, providing a tailored approach for treating apnea of prematurity in this population.

The model identified weight and post-natal age as key factors influencing caffeine clearance and distribution, which can help optimize individualized treatment for Chinese premature infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic study of caffeine citrate in Chinese premature infants with apnea. Guo, A., Zhu, Z., Xue, J., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Clinical effect and safety of different maintenance doses of caffeine citrate in treatment of apnea in very low birth weight preterm infants: a prospective randomized controlled trial]. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy of caffeine in treatment of apnea in the low-birth-weight infant. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Caffeine Citrate for Apnea of Prematurity: A Prospective, Open-Label, Single-Arm Study in Chinese Neonates. [2020]

5. China pubmed.ncbi.nlm.nih.gov

[Comparison of the efficacy of domestic and imported caffeine citrate in the treatment of apnea in preterm infants: a prospective randomized double-blind controlled trial]. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic study of caffeine citrate in Chinese premature infants with apnea. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

Early high-dose caffeine citrate for extremely preterm infants: Neonatal and neurodevelopmental outcomes. [2021]

8. Norway pubmed.ncbi.nlm.nih.gov

Aminophylline versus caffeine citrate for apnea and bradycardia prophylaxis in premature neonates. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the Use of Caffeine Citrate Maintenance Doses >5 mg/kg/day in Preterm Neonates for Apnea of Prematurity. [2021]