Neonatal ApneaPhase 2COFIE trailNCT07216365
Caffeine Optimization for Oxygen Saturation Index in ELBW Infants
A Phase 2 study testing Caffeine Citrate in people with Neonatal Apnea and Infants, run by University of Rochester at 1 site in United States.
Trial summary
The goal of this clinical trial is to determine whether a higher dose of caffeine citrate can improve breathing and reduce health complications in extremely premature infants, specifically those born before 28 weeks of pregnancy, known as ELGAN infants. Read more about this study
- Who is it for?
- Ages 0 days to 27 weeks
- Conditions the study is for
- Neonatal Apnea, Infants
- What is being tested?
- Caffeine Citrate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2026to 1 Sep 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 days to 27 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- URMC Inborn Newborn infants born with gestational age of 22 weeks 0 days - 27 weeks 6 days or infants OR ≥ 28 weeks with a birthweight < 1000 grams
Who cannot join
- Hepatic failure, spontaneous intestinal perforation, necrotizing enterocolitis, Anticipated major congenital or genetic anomalies, infants not anticipated to survive beyond 72 hours, infants with mothers that are non-English speaking or <18 years old at time of enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Rochester Medical Center
Rochester, New York, 14642
Stephanie Vachon, DO, (585) 275-4174, stephanie_vachon@urmc.rochester.edu
About this study
Official title: Caffeine Optimization for Oxygen Saturation Index in ELBW Infants (COFIE Trial)
The goal of this clinical trial is to determine whether a higher dose of caffeine citrate can improve breathing and reduce health complications in extremely premature infants, specifically those born before 28 weeks of pregnancy, known as ELGAN infants. These babies often struggle with breathing due to underdeveloped lungs, and caffeine is commonly used to help support their respiratory function. However, the most effective and safest dose has not yet been clearly established.
The study aims to answer two main questions: Does a higher maintenance dose of caffeine (10 mg/kg) lead to better oxygenation, as measured by the Oxygen Saturation Index (OSI), compared to the standard dose (5 mg/kg)? And does the higher dose reduce the risk of serious complications such as lung disease, brain injury, or death-without causing more side effects like fast heart rate, high blood pressure, or poor growth?
Read more
To answer these questions, researchers will compare two groups of infants: one receiving the high-dose caffeine treatment and the other receiving the standard dose. This comparison will help determine if the higher dose leads to better outcomes without increased risk.
Participants will begin caffeine treatment once they have regained their birth weight and are at least seven days old. They will be randomly assigned to receive either the high or standard caffeine dose and will be followed until caffeine is stopped or they are discharged from the hospital. During this time, researchers will monitor each infant's oxygenation levels, need for breathing support, signs of common complications, growth and feeding progress, and any side effects. Before discharge, each infant's motor development will also be assessed using a tool called the Test of Infant Motor Performance (TIMP).
This study could help define the most effective caffeine dosing strategy for supporting extremely premature infants and improving their short-term health outcomes.
- Conditions
- Neonatal Apnea, Infants
- Being tested
- Caffeine Citrate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine CitrateDrug
High Dose Group:
Caffeine citrate administered as a 20 mg/kg loading dose followed by a 10 mg/kg/day maintenance dose starting at 7 days of life. Dose escalation up to 12.5 mg/kg/day may be performed based on clinical indications. The drug is administered either intravenously or orally in a blinded fashion.
Standard Dose Group:
Caffeine citrate administered as a 20 mg/kg loading dose followed by a 5 mg/kg/day maintenance dose starting at 7 days of life. Dose escalation up to 7.5 mg/kg/day may be performed based on clinical indications. The drug is administered either intravenously or orally in a blinded fashion.
| Study group | Role | What they receive |
|---|---|---|
| High Dose Caffeine Arm | Experimental | Infants randomized to the high dose caffeine arm will receive an initial standard loading dose of 20 mg/kg caffeine citrate. Beginning at 7 days of life, they will receive a maintenance dose of 10 mg/kg/day caffeine citrate. Dose escalation may be performed at the discretion of the clinical team, with a maximum maintenance dose of 12.5 mg/kg/day if clinically indicated. Caffeine will be administered IV or PO at a 1:1 ratio and prepared in a blinded fashion. Receives: Drug: Caffeine Citrate |
| Standard Dose Caffeine Arm | Active comparator | Infants randomized to the standard dose caffeine arm will receive an initial loading dose of 20 mg/kg caffeine citrate. Beginning at 7 days of life, they will receive a maintenance dose of 5 mg/kg/day. Dose escalation may occur at the discretion of the clinical team, with a maximum maintenance dose of 7.5 mg/kg/day. Caffeine will be administered IV or PO at a 1:1 ratio and prepared in a blinded fashion. Receives: Drug: Caffeine Citrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Oxygen Saturation Index (OSI) per Patient Over First 56 Days
The OSI is calculated as (FiO₂ × MAP × 100) / SpO₂. The average OSI per patient will be calculated from randomization through the first 56 days or until caffeine is discontinued or the patient is discharged. Higher OSI values indicate worse oxygenation.
Measured: From Randomization to Day 56 or Caffeine Discontinuation
Total Duration of Respiratory Support
Total number of days each patient receives any respiratory support, including invasive ventilation, CPAP, or supplemental oxygen.
Measured: From Randomization to 1 year
Total Incidence of Severe Bronchopulmonary Dysplasia (BPD)
Number of infants diagnosed with severe BPD based on NICHD criteria.
Measured: From Randomization to 1 year
Total Incidence of Severe Intraventricular Hemorrhage or Periventricular Leukomalacia (IVH/PVL)
Number of infants diagnosed with severe IVH (Grade III/IV) or PVL based on cranial imaging.
Measured: From Randomization to 1 year
Total Length of NICU Stay
Total number of days each infant remains in the NICU from birth until discharge.
Measured: Birth to 1 year
Total Number of Infant Deaths
Number of infants who die before NICU discharge.
Measured: From Randomization to 1 year
Total Test of Infant Motor Performance (TIMP) Score Prior to Discharge
TIMP is a 42-item motor development assessment. Each item scores from 0 to 6. Total scores range from 0 to 252. Higher scores indicate better motor performance.
Measured: Prior to NICU Discharge
Total Duration of SpO₂ Below Threshold (Intermittent Hypoxia)
Cumulative minutes with SpO₂ below target threshold, derived from Neo-DReAMS repository.
Measured: From Randomization through Day 56
Total Time with Heart Rate >180 bpm (Tachycardia)
Total minutes with heart rate exceeding 180 bpm recorded via monitor.
Measured: From Randomization to 1 year
Total Growth Parameter Z-Scores (Length, Weight, Head Circumference)
Growth will be assessed using Fenton z-scores. Higher scores reflect better growth relative to gestational norms.
Measured: From Randomization to 1 year
Total Osteopenia Markers (Alkaline Phosphatase, Calcium, Phosphorus)
Osteopenia assessed by abnormal lab values: alkaline phosphatase >500 IU/L, abnormal calcium or phosphorus. Abnormal values per infant will be summed.
Measured: From Randomization to 1 year
Total Incidence of Hypertension (>95th Percentile)
Number of days with blood pressure >95th percentile for gestational age.
Measured: From Randomization to 1 year
Total Time to Full Enteral Feeds
Days from birth until the infant reaches 120 mL/kg/day enteral nutrition.
Measured: From Randomization to 1 year
Total Number of NPO Periods >24 Hours
Number of times infant is NPO (nothing by mouth) for more than 24 hours.
Measured: From Randomization through NICU Discharge
Total Incidence of Necrotizing Enterocolitis (NEC)
Number of infants diagnosed with NEC (Bell's stage II or higher).
Measured: From Randomization to 1 year
Total Incidence of Spontaneous Intestinal Perforation (SIP)
Number of infants with radiographically or surgically confirmed SIP.
Measured: From Randomization to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2025
- Study start15 Jul 2026
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neonatal ApneaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stephanie Vachon, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07216365
- Sponsor's protocol ID
- STUDY00011029
- Acronym
- COFIE trail
- Status last verified
- Jul 2026
- First submitted
- 5 Sep 2025
- Last updated
- 29 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Caffeine Optimization for Oxygen Saturation Index in ELBW Infants (COFIE Trial)
- ClinicalTrials.gov ID
- NCT07216365
- Acronym / sponsor ID
- COFIE trail / STUDY00011029
- Conditions
- Neonatal Apnea, Infants
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- 15 Jul 2026 (actual)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 1 Sep 2029 (estimated)
- First posted
- 14 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to determine whether a higher dose of caffeine citrate can improve breathing and reduce health complications in extremely premature infants, specifically those born before 28 weeks of pregnancy, known as ELGAN infants. These babies often struggle with breathing due to underdeveloped lungs, and caffeine is commonly used to help support their respiratory function. However, the most effective and safest dose has not yet been clearly established.
The study aims to answer two main questions: Does a higher maintenance dose of caffeine (10 mg/kg) lead to better oxygenation, as measured by the Oxygen Saturation Index (OSI), compared to the standard dose (5 mg/kg)? And does the higher dose reduce the risk of serious complications such as lung disease, brain injury, or death-without causing more side effects like fast heart rate, high blood pressure, or poor growth?
To answer these questions, researchers will compare two groups of infants: one receiving the high-dose caffeine treatment and the other receiving the standard dose. This comparison will help determine if the higher dose leads to better outcomes without increased risk.
Participants will begin caffeine treatment once they have regained their birth weight and are at least seven days old. They will be randomly assigned to receive either the high or standard caffeine dose and will be followed until caffeine is stopped or they are discharged from the hospital. During this time, researchers will monitor each infant's oxygenation levels, need for breathing support, signs of common complications, growth and feeding progress, and any side effects. Before discharge, each infant's motor development will also be assessed using a tool called the Test of Infant Motor Performance (TIMP).
This study could help define the most effective caffeine dosing strategy for supporting extremely premature infants and improving their short-term health outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High Dose Caffeine Arm | Experimental | Drug: Caffeine CitrateInfants randomized to the high dose caffeine arm will receive an initial standard loading dose of 20 mg/kg caffeine citrate. Beginning at 7 days of life, they will receive a maintenance dose of 10 mg/kg/day caffeine citrate. Dose escalation may be performed at the discretion of the clinical team, with a maximum maintenance dose of 12.5 mg/kg/day if clinically indicated. Caffeine will be administered IV or PO at a 1:1 ratio and prepared in a blinded fashion. |
| Standard Dose Caffeine Arm | Active comparator | Drug: Caffeine CitrateInfants randomized to the standard dose caffeine arm will receive an initial loading dose of 20 mg/kg caffeine citrate. Beginning at 7 days of life, they will receive a maintenance dose of 5 mg/kg/day. Dose escalation may occur at the discretion of the clinical team, with a maximum maintenance dose of 7.5 mg/kg/day. Caffeine will be administered IV or PO at a 1:1 ratio and prepared in a blinded fashion. |
Who may qualify
- Ages
- 0 days to 27 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- URMC Inborn Newborn infants born with gestational age of 22 weeks 0 days - 27 weeks 6 days or infants OR ≥ 28 weeks with a birthweight < 1000 grams
Key exclusion criteria (1 listed)
- Hepatic failure, spontaneous intestinal perforation, necrotizing enterocolitis, Anticipated major congenital or genetic anomalies, infants not anticipated to survive beyond 72 hours, infants with mothers that are non-English speaking or <18 years old at time of enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine CitrateHigh Dose Group: Caffeine citrate administered as a 20 mg/kg loading dose followed by a 10 mg/kg/day maintenance dose starting at 7 days of life. Dose escalation up to 12.5 mg/kg/day may be performed based on clinical indications. The drug is administered either intravenously or orally in a blinded fashion. Standard Dose Group: Caffeine citrate administered as a 20 mg/kg loading dose followed by a 5 mg/kg/day maintenance dose starting at 7 days of life. Dose escalation up to 7.5 mg/kg/day may be performed based on clinical indications. The drug is administered either intravenously or orally in a blinded fashion. | Drug | High Dose Caffeine Arm, Standard Dose Caffeine Arm |
Primary outcome
Average Oxygen Saturation Index (OSI) per Patient Over First 56 Days
Time frame: From Randomization to Day 56 or Caffeine Discontinuation
The OSI is calculated as (FiO₂ × MAP × 100) / SpO₂. The average OSI per patient will be calculated from randomization through the first 56 days or until caffeine is discontinued or the patient is discharged. Higher OSI values indicate worse oxygenation.
Total Duration of Respiratory Support
Time frame: From Randomization to 1 year
Total number of days each patient receives any respiratory support, including invasive ventilation, CPAP, or supplemental oxygen.
Total Incidence of Severe Bronchopulmonary Dysplasia (BPD)
Time frame: From Randomization to 1 year
Number of infants diagnosed with severe BPD based on NICHD criteria.
Total Incidence of Severe Intraventricular Hemorrhage or Periventricular Leukomalacia (IVH/PVL)
Time frame: From Randomization to 1 year
Number of infants diagnosed with severe IVH (Grade III/IV) or PVL based on cranial imaging.
Total Length of NICU Stay
Time frame: Birth to 1 year
Total number of days each infant remains in the NICU from birth until discharge.
Total Number of Infant Deaths
Time frame: From Randomization to 1 year
Number of infants who die before NICU discharge.
Total Test of Infant Motor Performance (TIMP) Score Prior to Discharge
Time frame: Prior to NICU Discharge
TIMP is a 42-item motor development assessment. Each item scores from 0 to 6. Total scores range from 0 to 252. Higher scores indicate better motor performance.
Total Duration of SpO₂ Below Threshold (Intermittent Hypoxia)
Time frame: From Randomization through Day 56
Cumulative minutes with SpO₂ below target threshold, derived from Neo-DReAMS repository.
Total Time with Heart Rate >180 bpm (Tachycardia)
Time frame: From Randomization to 1 year
Total minutes with heart rate exceeding 180 bpm recorded via monitor.
Total Growth Parameter Z-Scores (Length, Weight, Head Circumference)
Time frame: From Randomization to 1 year
Growth will be assessed using Fenton z-scores. Higher scores reflect better growth relative to gestational norms.
Total Osteopenia Markers (Alkaline Phosphatase, Calcium, Phosphorus)
Time frame: From Randomization to 1 year
Osteopenia assessed by abnormal lab values: alkaline phosphatase >500 IU/L, abnormal calcium or phosphorus. Abnormal values per infant will be summed.
Total Incidence of Hypertension (>95th Percentile)
Time frame: From Randomization to 1 year
Number of days with blood pressure >95th percentile for gestational age.
Total Time to Full Enteral Feeds
Time frame: From Randomization to 1 year
Days from birth until the infant reaches 120 mL/kg/day enteral nutrition.
Total Number of NPO Periods >24 Hours
Time frame: From Randomization through NICU Discharge
Number of times infant is NPO (nothing by mouth) for more than 24 hours.
Total Incidence of Necrotizing Enterocolitis (NEC)
Time frame: From Randomization to 1 year
Number of infants diagnosed with NEC (Bell's stage II or higher).
Total Incidence of Spontaneous Intestinal Perforation (SIP)
Time frame: From Randomization to 1 year
Number of infants with radiographically or surgically confirmed SIP.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Caffeine Citrate in people with Neonatal Apnea and Infants, run by University of Rochester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stephanie C Vachon, DO ((585) 275-4174, stephanie_vachon@urmc.rochester.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Oxygen Saturation Index (OSI) per Patient Over First 56 Days (time frame: From Randomization to Day 56 or Caffeine Discontinuation). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2026.