Caffeine for Primary Apnea of Prematurity

(MoCHA Trial)

No longer recruiting at 15 trial locations

Overseen By Abhik Das, PhD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: NICHD Neonatal Research Network

Must be taking: Caffeine citrate

Disqualifiers: Respiratory therapy, Apnea monitor, Congenital heart disease, Neuromuscular conditions, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 48 weeks PMA

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine how continuing caffeine citrate treatment both in the hospital and at home affects the hospital stay for moderately preterm infants with resolved apnea of prematurity. Apnea of prematurity is a condition where newborns stop breathing for short periods. The trial compares caffeine citrate to a placebo (a sugar pill with no active medicine) to evaluate which is more effective. Infants born between 29 to 33 weeks, who recently stopped caffeine treatment and are not on respiratory support, may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does mention that participants should be receiving caffeine treatment or have just stopped it. It seems like the focus is on caffeine treatment, so other medications might not be affected.

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

Research shows that caffeine citrate is generally safe for premature babies. Studies have found it to be well-tolerated when used long-term in babies born before 33 weeks. Some reports mention serious but rare side effects, such as lung problems (bronchopulmonary dysplasia) and intestinal issues (necrotizing enterocolitis), but these are uncommon.

A review of safety data found a low risk of death, about 2%, with other health issues also being rare. Caffeine citrate has been used successfully in hospitals to reduce breathing problems in preterm babies, yielding positive results.

Overall, existing research suggests that caffeine citrate is generally safe for preterm babies, though it carries some risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about caffeine citrate for treating apnea in moderately preterm infants because it offers a unique home-based approach. Unlike standard treatments, which are usually administered only in the hospital, caffeine citrate can be continued at home, providing consistent therapy during a crucial period after discharge. This could potentially lead to better outcomes by reducing apnea episodes more effectively in this vulnerable population. Additionally, caffeine citrate is well-known and has a proven safety profile, which makes it a promising candidate for this new application.

What evidence suggests that caffeine citrate is effective for reducing hospitalization days in preterm infants?

Research has shown that caffeine citrate, which participants in this trial may receive, helps treat apnea of prematurity, a condition where premature babies briefly stop breathing. One study found that a standard dose of caffeine greatly reduced the number of these breathing pauses. Another study showed that caffeine treatment improved survival rates without causing developmental issues in babies. Additionally, caffeine citrate offers long-term benefits for movement skills when used early in life. These findings suggest caffeine citrate can be a helpful treatment for premature babies with apnea. ^{3 6 7 8 9}

Who Is on the Research Team?

Waldemar Carlo, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

Inclusion Criteria

≤35 6/7 weeks post-menstrual age at the time of randomization

Inborn and outborn infants of 29 0/7 to 33 6/7 weeks gestational age at birth

Receiving caffeine with plan to discontinue treatment or just discontinued caffeine treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Infants receive caffeine citrate or placebo daily in the hospital, starting within 72 hours of open label caffeine discontinuation

Up to 48 weeks PMA

Daily administration in hospital

Home Treatment

Infants continue on the same dose of caffeine citrate or placebo at home for the first 28 days after hospital discharge

4 weeks

Weekly contact by research team

Follow-up

Participants are monitored for safety and effectiveness after treatment, with biweekly contact during weeks 5 to 8 post-discharge

4 weeks

Biweekly contact by research team

What Are the Treatments Tested in This Trial?

Interventions

• Caffeine Citrate
• Placebo

How Is the Trial Designed?

Group I: Caffeine Citrate Experimental Treatment 1 Intervention

Caffeine citrate at 10 mg/kg/dose (5 mg/kg caffeine base) daily, in hospital. Infants will continue at home on the same dose of caffeine citrate for the first 28 days after hospital discharge.

Group II: Placebo Placebo Group 1 Intervention

Placebo contains all of the excipients except for the active ingredient, caffeine citrate, (a volume equivalent to 10 mg/kg of caffeine citrate) and given daily. Infants will be continued at home on the same dose of placebo for the first 28 days after hospital discharge.

Who Is Running the Clinical Trial?

NICHD Neonatal Research Network

Lead Sponsor

Trials

62

Recruited

209,000+

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

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

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]

Caffeine citrate injection remains stable in various intravenous admixtures and parenteral nutrition solutions when stored at room temperature for up to 24 hours.

This stability suggests that caffeine citrate can be safely used in clinical settings without concerns of degradation during this time frame.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability of caffeine citrate injection in intravenous admixtures and parenteral nutrition solutions. Nahata, MC., Zingarelli, J., Durrell, DE.[2019]

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]

Citations

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

Caffeine therapy in preterm infants - PMC - PubMed Central Prior to the CAP trial, a loading dose of 50 mg/kg caffeine citrate (25 mg/kg caffeine base) was shown to be more effective in reducing apneic episodes within ...

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

Caffeine and preterm infants: multiorgan effects ... Caffeine citrate is effective in the treatment of AOP using standard dosing (loading dose 20 mg/kg, maintenance 5–10 mg/kg/day) and is associated with long- ...

3. jpeds.com jpeds.com/article/S0022-3476(23)00336-0/fulltext

Caffeine for Apnea of Prematurity: Too Much or Too Little ... Post hoc analyses suggested that at least 25% and possibly 100% of the beneficial effect of neonatal caffeine therapy on motor function 11 years ...

4. 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 ...

5. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.00076/full

Caffeine Citrate for Apnea of Prematurity: A Prospective ... Results: A total of 247 neonates received the loading dose, who had a significant reduction from baseline of 3.9 events (p < 0.001) in the mean ...

6. 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 ...

7. fda.gov fda.gov/media/181638/download

Cafcit Pediatric Postmarketing Safety Review Six cases described fatal outcomes in patients who were not exposed to caffeine citrate injection. Five cases described neonatal and infant ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6661003/

Dosing and Safety of Off-label Use of Caffeine Citrate in ... Incidences of clinical events on day of caffeine citrate exposure were: death 2%, patent ductus arteriosus ligation 12%, and medical and surgical necrotizing ...

9. 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 ...