Caffeine Optimization for Oxygen Saturation Index in ELBW Infants

NCT07216365 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00000000
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Infants; Neonatal Apnea

Outcome Measures

Primary Outcomes (16)

• 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.

  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.

  From Randomization to 1 year

• Total Incidence of Severe Bronchopulmonary Dysplasia (BPD)

  Number of infants diagnosed with severe BPD based on NICHD criteria.

  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.

  From Randomization to 1 year

• Total Length of NICU Stay

  Total number of days each infant remains in the NICU from birth until discharge.

  Birth to 1 year

• Total Number of Infant Deaths

  Number of infants who die before NICU discharge.

  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.

  Prior to NICU Discharge

• Total Duration of SpO₂ Below Threshold (Intermittent Hypoxia)

  Cumulative minutes with SpO₂ below target threshold, derived from Neo-DReAMS repository.

  From Randomization through Day 56

• Total Time with Heart Rate >180 bpm (Tachycardia)

  Total minutes with heart rate exceeding 180 bpm recorded via monitor.

  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.

  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.

  From Randomization to 1 year

• Total Incidence of Hypertension (>95th Percentile)

  Number of days with blood pressure \>95th percentile for gestational age.

  From Randomization to 1 year

• Total Time to Full Enteral Feeds

  Days from birth until the infant reaches 120 mL/kg/day enteral nutrition.

  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.

  From Randomization through NICU Discharge

• Total Incidence of Necrotizing Enterocolitis (NEC)

  Number of infants diagnosed with NEC (Bell's stage II or higher).

  From Randomization to 1 year

• Total Incidence of Spontaneous Intestinal Perforation (SIP)

  Number of infants with radiographically or surgically confirmed SIP.

  From Randomization to 1 year

Study Arms (2)

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.

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.

Drug: Caffeine Citrate

Interventions

Caffeine Citrate DRUG

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.

High Dose Caffeine Arm; Standard Dose Caffeine Arm

Eligibility Criteria

• Age: 0 Days - 27 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Rochester: lead

MeSH Terms

Interventions

caffeine citrate

Central Study Contacts

Stephanie C Vachon, DO

CONTACT

(585) 275-4174; stephanie_vachon@urmc.rochester.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor - Department of Pediatrics

Study Record Dates

• First Submitted: September 5, 2025
• First Posted: October 14, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share