Caffeine for Preterm Birth

Overseen By Elena Alfaro, CCRP

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Wisconsin, Madison

Must be taking: Caffeine

Disqualifiers: Congenital anomalies, Chromosomal anomalies, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 14 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether extra caffeine citrate (a form of caffeine) can improve kidney oxygen levels and reduce the risk of acute kidney injury in preterm babies. Researchers aim to determine if this added caffeine is safe for the brain while offering these benefits. Babies born before 30 weeks, already receiving caffeine and able to have their oxygen levels monitored, might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that caffeine citrate has been safely used in premature babies for some time. One study found that giving caffeine to preterm babies can help reduce health issues like bronchopulmonary dysplasia, a lung condition, and other problems. Another study confirmed that caffeine citrate is safe for very early-born infants, before 33 weeks, even when used for longer periods.

Further research indicates that babies who received caffeine within two days of birth showed better development by 18 to 24 months of age. Although some findings about caffeine's use for preventing breathing pauses in preterm babies are mixed, the overall evidence supports its safety.

Since this trial is in the second phase, researchers generally expect the treatment to be safe, but more detailed safety information is being studied. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for preterm birth that often focus on hormonal therapies or interventions to delay labor, caffeine citrate is unique because it taps into a different mechanism, acting as a central nervous system stimulant. Researchers are excited about caffeine citrate because it has the potential to improve respiratory function and stimulate breathing in preterm infants, which is crucial for their development. This treatment is derived from a commonly consumed substance, making it familiar and potentially safer. Additionally, caffeine citrate can be administered orally or intravenously, offering flexibility in treatment administration.

What evidence suggests that this trial's treatments could be effective for preterm birth?

Research has shown that caffeine citrate, which participants in this trial may receive, can benefit premature babies. Studies have found that it reduces the risk of serious lung problems, such as bronchopulmonary dysplasia (BPD), and common heart issues, like patent ductus arteriosus (PDA). Higher doses of caffeine have been linked to improved movement skills and fewer developmental issues. Long-term studies found that babies treated with caffeine had better survival rates without brain development problems. Caffeine citrate may improve survival and reduce the risk of conditions like cerebral palsy and learning delays. ^{1 6 7 8 9}

Who Is on the Research Team?

Matthew W Harer, MD

Principal Investigator

UW School of Medicine and Public Health

Are You a Good Fit for This Trial?

This trial is for preterm babies born before 30 weeks of gestation, who are already receiving caffeine treatment. It's designed to see if extra caffeine can help their kidneys without harming the brain. Babies must be more than 48 hours old but less than 14 days old to participate.

Inclusion Criteria

Gestational age at birth between 23 0/7 and 29 6/7 weeks

Able to have near-infrared spectroscopy (NIRS) monitoring of cerebral and kidney oxygenation

Indwelling umbilical arterial catheter (UAC), umbilical venous catheter (UVC), peripheral arterial line (PAL), or peripherally inserted central catheter (PICC) already in place that can draw blood

Exclusion Criteria

Not suitable for study participation due to other reasons at the discretion of the investigators

I do not have major birth defects in my brain, heart, lungs, or kidneys.

I have a known or suspected genetic abnormality.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-4 days

1 visit (in-person)

Treatment

Participants receive either additional caffeine citrate or placebo between 48 hours and 14 days of life

14 days

Daily monitoring (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment until NICU discharge or 6 months of age

Up to 6 months

Regular monitoring (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Caffeine citrate
• Placebo

Trial Overview The study tests whether an additional dose of caffeine citrate (20 mg/kg IV bolus) improves kidney function in premature infants compared to a placebo. These infants are already on a standard caffeine treatment regimen from day one.

How Is the Trial Designed?

Group I: Arm 1: Caffeine Experimental Treatment 1 Intervention

Group II: Arm 3: Control Active Control 1 Intervention

Group III: Arm 2: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4637812/

Caffeine therapy in preterm infants - PMC - PubMed Central A recent study, demonstrated that early caffeine initiation is associated with reduced neonatal morbidity, including a decreased incidence of BPD and of patent ...

2. nature.com nature.com/articles/s41372-024-01939-x

Caffeine for apnea and prevention of neurodevelopmental ... Caffeine administered to preterm infants probably reduces BPD, PDA, and motor impairment, with higher doses probably conferring additional ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa073679

Long-Term Effects of Caffeine Therapy for Apnea ... Caffeine significantly improved the rate of survival without neurodevelopmental disability at a corrected age of 18 to 21 months. Of the 937 infants assigned to ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9098661/

Five-year outcomes of premature infants randomized to ... At standard doses, caffeine citrate improves survival and lowers the risk of subsequent cerebral palsy, motor impairment, cognitive delays, and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04001712

Effect of Early Use of Caffeine Citrate in Preterm Neonates This may be indicated by a specific age or the following age groups: The age groups are: Child (birth-17); Adult (18-64); Older Adult (65+) ... A measure of all ...

6. nature.com nature.com/articles/s41390-025-04066-1

Caffeine and preterm infants: multiorgan effects ... A Cochrane review showed insufficient evidence to support prophylactic use of caffeine citrate in preterm neonates to prevent AOP, although it ...

7. jpeds.com jpeds.com/article/S0022-3476(19)30510-4/abstract

Dosing and Safety of Off-label Use of Caffeine Citrate in ... Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK564965/

Safety and Efficacy of Caffeine Citrate in Premature Infants The data provides evidence that use of caffeine citrate in premature infants <33 weeks for longer durations is safe. 12.1. Retrospective Analyses; 12.2. CAP ...

9. publications.aap.org publications.aap.org/pediatrics/article/143/1/e20181348/37278/Early-Caffeine-Administration-and

Early Caffeine Administration and Neurodevelopmental ... Preterm neonates who received caffeine (within 2 days of birth) had lower odds of sNDI at 18 to 24 months' CA.