Preterm BirthPhase 2CARES-PilotNCT07456670
Caffeine for Infants Born at 28 to 34 Weeks Receiving Respiratory Support
A Phase 2 study testing Caffeine in people with Preterm Birth and Caffeine, run by Queen's University at 1 site in Canada.
Trial summary
The goal of this pilot clinical trial is to test if it is possible to conduct a larger study on the use of caffeine in preterm infants who need help with their breathing. It will also look at whether caffeine helps these infants get healthy enough to leave the hospital sooner. Read more about this study
- Who is it for?
- Ages 0 to 28 days
- Conditions the study is for
- Preterm Birth, Caffeine, Neonatal Outcomes
- What is being tested?
- Caffeine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 62 participants
- Where
- 1 siteCanada
- Study dates
- 1 Apr 2026to 31 Mar 2028
- 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 to 28 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infant born at a gestational age between 28+0 and 34+6 weeks.
- Admitted to the Neonatal Intensive Care Unit (NICU) within the first 72 hours of life.
- Requiring either invasive respiratory support (mechanical ventilation) or non-invasive respiratory support (e.g., CPAP, High Flow Nasal Cannula) within the first 72 hours of life.
- Informed consent obtained from parent(s) or legal guardian(s).
Who cannot join
- Presence of dysmorphic features or major congenital malformations that adversely affect life expectancy.
- Known or strongly suspected cyanotic heart disease.
- Infants born at <28 weeks' gestational age (due to high risk of apnea requiring routine caffeine).
- Late preterm infants born at ≥35+0 weeks' gestational age (due to short NICU stay not allowing for a safe caffeine-free period before discharge).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Caffeine Therapy in Preterm Infants Born at 28-34 Weeks: A Pilot Placebo-Controlled Randomized Controlled Trial
The goal of this pilot clinical trial is to test if it is possible to conduct a larger study on the use of caffeine in preterm infants who need help with their breathing. It will also look at whether caffeine helps these infants get healthy enough to leave the hospital sooner.
The main questions the researchers aim to answer are:
Read more
Can the investigators successfully recruit and keep enough participants in the study? Do the medical teams follow the study drug instructions correctly? Does caffeine reduce the total time infants spend in the Neonatal Intensive Care Unit (NICU)? Researchers will compare caffeine to a placebo (a look-alike substance with no active medicine) to see if caffeine is a helpful treatment for babies born between 28 and 34 weeks of gestation who are using a breathing machine or oxygen.
Participants will:
Be randomly assigned to receive either caffeine or a placebo through an IV or a feeding tube.
Receive the study treatment once a day as long as they require respiratory support (and for 24 hours after they stop).
Be monitored by the research team for clinical outcomes like feeding progress, breathing stability, and growth until they are discharged from the hospital.
Read the detailed description
Despite the widespread use of caffeine for extremely preterm infants, a significant knowledge gap exists regarding its efficacy for infants (28+0 to 34+6 weeks' gestation) who require respiratory support. This patient population is at increased risk for respiratory morbidity and prolonged hospitalization, yet clinical practice regarding caffeine use remains highly variable.
The CARES-Pilot is a single-center, pilot randomized controlled trial (RCT) designed to assess the feasibility of a larger, definitive trial. The long-term goal of the definitive trial is to determine if routine caffeine administration reduces the time to discharge alive from the NICU.
This pilot study utilizes a double-blind, placebo-controlled, parallel-group design. Eligible infants are those born between 28+0 and 34+6 weeks of gestation who require invasive or non-invasive respiratory support within the first 72 hours of life. Participants are randomized to receive either caffeine base (10 mg/kg loading dose, followed by 5 mg/kg daily maintenance) or an equivalent volume of normal saline (placebo).
The primary focus of this pilot phase is to evaluate four key feasibility outcomes using a "traffic light" approach with pre-specified progression criteria:
Recruitment and Eligibility: Assessing the proportion of eligible infants whose parents provide consent and are successfully randomized.
Treatment Fidelity: Monitoring adherence to the blinded treatment protocol by the clinical and pharmacy teams.
Retention: Evaluating the number of participants who complete the study through to the primary clinical endpoint.
Data Completeness: Ensuring the reliability of data collection for secondary clinical outcomes.
Secondary clinical objectives include measuring the time to discharge alive from the NICU (the planned primary outcome for the definitive trial), duration of respiratory support, time to full enteral feeds, and neurodevelopmental status at discharge using the Test of Infant Motor Performance (TIMP). This pilot will also explore the acceptability of the trial protocol among healthcare providers and parents through surveys and focus groups.
The findings from this pilot study will be used to refine the protocol, calculate a precise sample size for the definitive multicenter RCT, and determine the viability of expanding the study to other sites.
- Conditions
- Preterm Birth, Caffeine, Neonatal Outcomes
- Being tested
- Caffeine, Placebo
- Keywords
- Caffeine, Neonatal Intensive Care Unit, Prematurity, RCT, NICU, Pilot Study
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CaffeineDrug
Also called caffeine Base
Infants randomized to this arm will receive caffeine citrate administered as a 10 mg/kg loading dose (caffeine base equivalent), followed by a 5 mg/kg daily maintenance dose (caffeine base equivalent).
PlaceboOther
Infants randomized to this arm will receive 0.9% normal saline administered in a volume equivalent to the caffeine citrate arm. The placebo will be administered as a loading dose followed by a daily maintenance dose matching the volume and timing of the experimental protocol
| Study group | Role | What they receive |
|---|---|---|
| Caffeine Citrate Group | Experimental | Infants in this arm will receive a loading dose of caffeine base (10 mg/kg), followed by a daily maintenance dose (5 mg/kg). The study drug will be administered intravenously or enterally (once full oral feeds are established) until 24 hours after the successful weaning of respiratory support Receives: Drug: Caffeine |
| Placebo Group | Placebo comparator | Infants in this arm will receive an equivalent volume of 0.9% normal saline (placebo) instead of caffeine. The loading dose and daily maintenance doses will follow the same schedule and administration routes (intravenous or enteral) as the experimental arm. The placebo will be administered until 24 hours after the successful weaning of respiratory support. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment/Eligibility Proportion
Ratio of enrolled/randomized infants to total eligible infants screened.
Measured: Through study completion, up to 24 months
Treatment Adherence Proportion
Percentage of per-protocol doses (caffeine/placebo) successfully administered
Measured: From randomization until 24 hours after weaning from respiratory support
Retention Proportion
Percentage of randomized infants who complete the study protocol until NICU discharge
Measured: Through study completion, up to 24 months
Secondary outcomes (26)
Time to Discharge Alive from the NICU
Hours from the time of randomization to the time of discharge alive from the NICU
Measured: From the date of randomization until the date of discharge alive from NICU, assessed up to 24 months
Parent/Guardian Acceptability
Frequency distribution of Likert-scale responses on the parent satisfaction survey
Measured: Within 7 days prior to infant's NICU discharge
Healthcare Provider Acceptability
Thematic analysis of healthcare provider focus group transcripts regarding protocol viability
Measured: Through recruitment completion, an average of 24 months
Data Completeness
Proportion of missing data points across all secondary clinical outcomes.
Measured: At the end of the recruitment period, approximately 24 months
Significant Apnea Frequency
Mean number of apneas per day requiring intervention (stimulation, or ventilation)
Measured: From randomization until 24 hours after weaning from respiratory support
Total Duration of Respiratory Support
Total hours spent on invasive and non-invasive mechanical ventilation
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months
Duration of Invasive Support
Total hours spent specifically on invasive mechanical ventilation (intubation)
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months
Time to Full Enteral Feeding
Hours from the first feed until the infant reaches the protocol-defined "full" enteral volume
Measured: From the date of first enteral feeding until the date when the targeted feeding volume is achieved, average of 14 days
Time to Full Oral Feeding
Hours from birth until the infant is successfully taking all feeds by mouth (no tube)
Measured: From the date of birth until the date of full oral feeding is achieved, an average of 6 weeks
Duration of Total Parenteral Nutrition (TPN)
Total number of days during which the infant received any volume of parenteral nutrition
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
PMA at Weaning
Mean post-menstrual age of the infant when respiratory support is successfully discontinued
Measured: At the time of weaning from respiratory support, an average of 4 to 6 weeks after birth
PMA at Discharge
Mean post-menstrual age of the infant at the time of discharge alive from the NICU.
Measured: At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age
Rate of New Invasive Ventilation
Proportion of infants not intubated at enrollment who require intubation during the study.
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months
In-hospital Mortality
Proportion of enrolled infants who die during their initial NICU stay.
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months
Test of Infant Motor Performance (TIMP) Score
Mean score on the Test of Infant Motor Performance (TIMP). Scores range from 0 to 142, with higher scores indicating better motor maturity and performance
Measured: At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age
Bronchopulmonary dysplasia (BPD)
Proportion of enrolled infants with BPD defined as: For infants born prior to 32 weeks of gestation, this will be defined as oxygen treatment for at least 28 days with oxygen need at 36 weeks' postmenstrual age or at discharge from the NICU, whichever occurs earlier. For infants born at 32 weeks or later, this will be defined as oxygen treatment at 56 days of life or at discharge from the NICU, whichever occurs earlier.
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Pulmonary Hemorrhage
Proportion of enrolled infants with pulmonary hemorrhage defined as the presence of sanguineous fluid in the trachea associated with clinical respiratory deterioration and new radiographic opacities.
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Pneumothorax
Proportion of enrolled infants with pneumothorax defined as accumulation of air in the pleural space, confirmed by chest radiograph, requires intervention such as needle aspiration or chest tube insertion
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Necrotizing Enterocolitis (NEC) Bell's Stage 2 or more
Proportion of enrolled infants with a diagnosis of NEC meeting at least Bell's Stage II criteria
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Gastrointestinal Surgery
Proportion of enrolled infants with any invasive surgical procedure related to the gastrointestinal tract, including laparotomy for NEC, intestinal resection, or the insertion of a peritoneal drain
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Intraventricular hemorrhage (IVH)
Proportion of enrolled infants with any grade of bleeding into the cerebral ventricular system of the brain. This will be graded according to the Papile classification (Grades I-IV) diagnosed by head imaging.
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Periventricular Leukomalacia (PVL)
Proportion of enrolled infants with localized areas of cystic necrosis in the periventricular white matter, diagnosed by serial cranial ultrasound or Magnetic Resonance Imaging (MRI)
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Seizure
Proportion of enrolled infants with clinical seizure identified by clinical observation
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Patent ductus arteriosus (PDA) Treatment
Proportion of enrolled infants who received a pharmacological therapy or surgical ligation intended to close a hemodynamically significant PDA.
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Retinopathy of Prematurity (ROP) Stage
Mean of the highest stage of RoP (Stages 1-5) recorded in either eye during the infant's hospital stay based on formal ophthalmological retinal examinations
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Late Onset Sepsis
Proportion of enrolled infants with a positive blood or cerebrospinal fluid culture obtained after day 3 (72 hours) of life in an infant with clinical signs of infection
Measured: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2026
- Study start1 Apr 2026 (estimated)
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies 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
- Model description
- A randomized, double-blind, 1:1 parallel-group allocation comparing a daily caffeine base to a matched saline placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Queen's University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eyad Bitar, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07456670
- Sponsor's protocol ID
- TRAQ 73767
- Acronym
- CARES-Pilot
- Status last verified
- Feb 2026
- First submitted
- 27 Feb 2026
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data sharing may be considered on a case-by-case basis upon reasonable request to the Principal Investigator, provided that the request does not conflict with the primary goals of the upcoming definitive trial or compromise participant privacy
Publications
Oliphant EA, Hanning SM, McKinlay CJD, Alsweiler JM. Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis. J Perinatol. 2024 Jun;44(6):785-801. doi: 10.1038/s41372-024-01939-x. Epub 2024 Mar 29.
PubMed 38553606Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
PubMed 16707748Iranpour R, Armanian AM, Miladi N, Feizi A. Effect of Prophylactic Caffeine on Noninvasive Respiratory Support in Preterm Neonates Weighing 1250-2000 g: A Randomized Controlled Trial. Arch Iran Med. 2022 Feb 1;25(2):98-104. doi: 10.34172/aim.2022.16.
PubMed 35429946Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res. 2017 Jan 26;17(1):88. doi: 10.1186/s12913-017-2031-8.
PubMed 28126032Lewis M, Bromley K, Sutton CJ, McCray G, Myers HL, Lancaster GA. Determining sample size for progression criteria for pragmatic pilot RCTs: the hypothesis test strikes back! Pilot Feasibility Stud. 2021 Feb 3;7(1):40. doi: 10.1186/s40814-021-00770-x.
PubMed 33536076Muehlbacher T, Gaertner VD, Bassler D. History of caffeine use in neonatal medicine and the role of the CAP trial. Semin Fetal Neonatal Med. 2020 Dec;25(6):101159. doi: 10.1016/j.siny.2020.101159. Epub 2020 Oct 21. No abstract available.
PubMed 33129702
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Caffeine Therapy in Preterm Infants Born at 28-34 Weeks: A Pilot Placebo-Controlled Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07456670
- Acronym / sponsor ID
- CARES-Pilot / TRAQ 73767
- Conditions
- Preterm Birth, Caffeine, Neonatal Outcomes
- Keywords
- Caffeine, Neonatal Intensive Care Unit, Prematurity, RCT, NICU, Pilot Study
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Queen's UniversityUniversity, hospital or other
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 6 Mar 2026 (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 pilot clinical trial is to test if it is possible to conduct a larger study on the use of caffeine in preterm infants who need help with their breathing. It will also look at whether caffeine helps these infants get healthy enough to leave the hospital sooner.
The main questions the researchers aim to answer are:
Can the investigators successfully recruit and keep enough participants in the study? Do the medical teams follow the study drug instructions correctly? Does caffeine reduce the total time infants spend in the Neonatal Intensive Care Unit (NICU)? Researchers will compare caffeine to a placebo (a look-alike substance with no active medicine) to see if caffeine is a helpful treatment for babies born between 28 and 34 weeks of gestation who are using a breathing machine or oxygen.
Participants will:
Be randomly assigned to receive either caffeine or a placebo through an IV or a feeding tube.
Receive the study treatment once a day as long as they require respiratory support (and for 24 hours after they stop).
Be monitored by the research team for clinical outcomes like feeding progress, breathing stability, and growth until they are discharged from the hospital.
Detailed description
Despite the widespread use of caffeine for extremely preterm infants, a significant knowledge gap exists regarding its efficacy for infants (28+0 to 34+6 weeks' gestation) who require respiratory support. This patient population is at increased risk for respiratory morbidity and prolonged hospitalization, yet clinical practice regarding caffeine use remains highly variable.
The CARES-Pilot is a single-center, pilot randomized controlled trial (RCT) designed to assess the feasibility of a larger, definitive trial. The long-term goal of the definitive trial is to determine if routine caffeine administration reduces the time to discharge alive from the NICU.
This pilot study utilizes a double-blind, placebo-controlled, parallel-group design. Eligible infants are those born between 28+0 and 34+6 weeks of gestation who require invasive or non-invasive respiratory support within the first 72 hours of life. Participants are randomized to receive either caffeine base (10 mg/kg loading dose, followed by 5 mg/kg daily maintenance) or an equivalent volume of normal saline (placebo).
The primary focus of this pilot phase is to evaluate four key feasibility outcomes using a "traffic light" approach with pre-specified progression criteria:
Recruitment and Eligibility: Assessing the proportion of eligible infants whose parents provide consent and are successfully randomized.
Treatment Fidelity: Monitoring adherence to the blinded treatment protocol by the clinical and pharmacy teams.
Retention: Evaluating the number of participants who complete the study through to the primary clinical endpoint.
Data Completeness: Ensuring the reliability of data collection for secondary clinical outcomes.
Secondary clinical objectives include measuring the time to discharge alive from the NICU (the planned primary outcome for the definitive trial), duration of respiratory support, time to full enteral feeds, and neurodevelopmental status at discharge using the Test of Infant Motor Performance (TIMP). This pilot will also explore the acceptability of the trial protocol among healthcare providers and parents through surveys and focus groups.
The findings from this pilot study will be used to refine the protocol, calculate a precise sample size for the definitive multicenter RCT, and determine the viability of expanding the study to other sites.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized, double-blind, 1:1 parallel-group allocation comparing a daily caffeine base to a matched saline placebo
| Arm | Type | Receives |
|---|---|---|
| Caffeine Citrate Group | Experimental | Drug: CaffeineInfants in this arm will receive a loading dose of caffeine base (10 mg/kg), followed by a daily maintenance dose (5 mg/kg). The study drug will be administered intravenously or enterally (once full oral feeds are established) until 24 hours after the successful weaning of respiratory support |
| Placebo Group | Placebo comparator | Other: PlaceboInfants in this arm will receive an equivalent volume of 0.9% normal saline (placebo) instead of caffeine. The loading dose and daily maintenance doses will follow the same schedule and administration routes (intravenous or enteral) as the experimental arm. The placebo will be administered until 24 hours after the successful weaning of respiratory support. |
Who may qualify
- Ages
- 0 to 28 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Infant born at a gestational age between 28+0 and 34+6 weeks.
- Admitted to the Neonatal Intensive Care Unit (NICU) within the first 72 hours of life.
- Requiring either invasive respiratory support (mechanical ventilation) or non-invasive respiratory support (e.g., CPAP, High Flow Nasal Cannula) within the first 72 hours of life.
- Informed consent obtained from parent(s) or legal guardian(s).
Key exclusion criteria (4 listed)
- Presence of dysmorphic features or major congenital malformations that adversely affect life expectancy.
- Known or strongly suspected cyanotic heart disease.
- Infants born at <28 weeks' gestational age (due to high risk of apnea requiring routine caffeine).
- Late preterm infants born at ≥35+0 weeks' gestational age (due to short NICU stay not allowing for a safe caffeine-free period before discharge).
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 |
|---|---|---|
| CaffeineAlso: caffeine BaseInfants randomized to this arm will receive caffeine citrate administered as a 10 mg/kg loading dose (caffeine base equivalent), followed by a 5 mg/kg daily maintenance dose (caffeine base equivalent). | Drug | Caffeine Citrate Group |
| PlaceboInfants randomized to this arm will receive 0.9% normal saline administered in a volume equivalent to the caffeine citrate arm. The placebo will be administered as a loading dose followed by a daily maintenance dose matching the volume and timing of the experimental protocol | Other | Placebo Group |
Primary outcome
Recruitment/Eligibility Proportion
Time frame: Through study completion, up to 24 months
Ratio of enrolled/randomized infants to total eligible infants screened.
Treatment Adherence Proportion
Time frame: From randomization until 24 hours after weaning from respiratory support
Percentage of per-protocol doses (caffeine/placebo) successfully administered
Retention Proportion
Time frame: Through study completion, up to 24 months
Percentage of randomized infants who complete the study protocol until NICU discharge
26 secondary outcomes
Time to Discharge Alive from the NICU
Time frame: From the date of randomization until the date of discharge alive from NICU, assessed up to 24 months
Parent/Guardian Acceptability
Time frame: Within 7 days prior to infant's NICU discharge
Healthcare Provider Acceptability
Time frame: Through recruitment completion, an average of 24 months
Data Completeness
Time frame: At the end of the recruitment period, approximately 24 months
Significant Apnea Frequency
Time frame: From randomization until 24 hours after weaning from respiratory support
Total Duration of Respiratory Support
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months
Duration of Invasive Support
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months
Time to Full Enteral Feeding
Time frame: From the date of first enteral feeding until the date when the targeted feeding volume is achieved, average of 14 days
Time to Full Oral Feeding
Time frame: From the date of birth until the date of full oral feeding is achieved, an average of 6 weeks
Duration of Total Parenteral Nutrition (TPN)
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
PMA at Weaning
Time frame: At the time of weaning from respiratory support, an average of 4 to 6 weeks after birth
PMA at Discharge
Time frame: At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age
Rate of New Invasive Ventilation
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months
In-hospital Mortality
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, assessed up to 24 months
Test of Infant Motor Performance (TIMP) Score
Time frame: At the time of NICU discharge, an average of 36 to 40 weeks post-menstrual age
Bronchopulmonary dysplasia (BPD)
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Pulmonary Hemorrhage
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Pneumothorax
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Necrotizing Enterocolitis (NEC) Bell's Stage 2 or more
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Gastrointestinal Surgery
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Intraventricular hemorrhage (IVH)
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Periventricular Leukomalacia (PVL)
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Seizure
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Patent ductus arteriosus (PDA) Treatment
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Retinopathy of Prematurity (ROP) Stage
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
Late Onset Sepsis
Time frame: From the date of randomization until the date of discharge alive from NICU or date of death from any cause, whichever came first, , an average of 36 to 40 weeks post-menstrual age
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 10 Mar 2026.
- Background: PubMed 38553606Oliphant EA, Hanning SM, McKinlay CJD, Alsweiler JM. Caffeine for apnea and prevention of neurodevelopmental impairment in preterm infants: systematic review and meta-analysis. J Perinatol. 2024 Jun;44(6):785-801. doi: 10.1038/s41372-024-01939-x. Epub 2024 Mar 29.
- Background: PubMed 16707748Schmidt B, Roberts RS, Davis P, Doyle LW, Barrington KJ, Ohlsson A, Solimano A, Tin W; Caffeine for Apnea of Prematurity Trial Group. Caffeine therapy for apnea of prematurity. N Engl J Med. 2006 May 18;354(20):2112-21. doi: 10.1056/NEJMoa054065.
- Background: PubMed 35429946Iranpour R, Armanian AM, Miladi N, Feizi A. Effect of Prophylactic Caffeine on Noninvasive Respiratory Support in Preterm Neonates Weighing 1250-2000 g: A Randomized Controlled Trial. Arch Iran Med. 2022 Feb 1;25(2):98-104. doi: 10.34172/aim.2022.16.
- Background: PubMed 28126032Sekhon M, Cartwright M, Francis JJ. Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework. BMC Health Serv Res. 2017 Jan 26;17(1):88. doi: 10.1186/s12913-017-2031-8.
- Background: PubMed 33536076Lewis M, Bromley K, Sutton CJ, McCray G, Myers HL, Lancaster GA. Determining sample size for progression criteria for pragmatic pilot RCTs: the hypothesis test strikes back! Pilot Feasibility Stud. 2021 Feb 3;7(1):40. doi: 10.1186/s40814-021-00770-x.
- Background: PubMed 33129702Muehlbacher T, Gaertner VD, Bassler D. History of caffeine use in neonatal medicine and the role of the CAP trial. Semin Fetal Neonatal Med. 2020 Dec;25(6):101159. doi: 10.1016/j.siny.2020.101159. Epub 2020 Oct 21. No abstract available.
- Individual participant dataSharing planned: Undecided. Data sharing may be considered on a case-by-case basis upon reasonable request to the Principal Investigator, provided that the request does not conflict with the primary goals of the upcoming definitive trial or compromise participant privacy
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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 in people with Preterm Birth and Caffeine, run by Queen's University at 1 site in Canada.
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 4 inclusion and 4 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: opening soon, as of the sponsor's last update on 10 Mar 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 Canada. 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. Some participants in this study may receive a placebo. 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 Eyad Bitar, MD (+1 (613) 548-6053, eyad.bitar@queensu.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment/Eligibility Proportion (time frame: Through study completion, up to 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07456670, which also lists 6 linked publications.
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 10 Mar 2026; AzTrials last refreshed its copy on 7 Nov 2026.