Caffeine Citrate to Improve Neonatal Outcomes.
- Registration Number
- NCT06972849
- Lead Sponsor
- University of Melbourne
- Brief Summary
The goal of this clinical trial to learn what dose/s of caffeine citrate works to treat preterm born babies who have episodes where they stop breathing. It will also learn about the safety of different doses of caffeine citrate for the variety of preterm-born babies that are prescribed this.
The main question it aims to answer is: Which dose is the optimal dose of caffeine citrate for very preterm babies to prevent short-term death and disease?
Researchers will compare three different doses of caffeine citrate, which are already used in clinical practice to treat breathing stoppages in preterm babies, to see which dose works best. No placebo will be used.
Participants will be given a 'loading' dose of caffeine citrate \<72 hours of life, and a smaller 'maintenance' dose once a day, for as long as the baby needs this.
This trial will be undertaken as part of the PLATIPUS trial (NCT06461429).
- Detailed Description
The BabyCCINO trial will compare the efficacy and safety of a higher, medium or lower-dose caffeine regimen in very preterm infants. It is a neonatal domain within the PLATIPUS adaptive platform trial (NCT06461429).
Apnoea of prematurity, which causes repeated episodes of low oxygen saturation, affects virtually all extremely preterm infants born \<28 weeks' gestation and more than half of those born 28-31 weeks' gestation. Apnoeic events are associated with poorer neurodevelopmental outcomes in infancy. Some very preterm infants also require mechanical ventilation due to apnoea, with an associated risk of bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity diagnosed at 36 weeks' post-menstrual age (PMA).
Caffeine is one of the most commonly prescribed drugs in neonatal medicine and reduces apnoea of prematurity. The largest trial of caffeine in very preterm infants, the Caffeine for Apnea of Prematurity (CAP) trial, found that caffeine improves important short-term respiratory outcomes and longer-term brain development compared with placebo. There is evidence from small clinical trials of more benefit from higher dose caffeine than that used in the CAP trial, however, potential side effects include jitteriness, tachycardia and feed intolerance. A higher rate of cerebellar haemorrhage was also reported in one small trial in infants who received a higher loading dose of 80 mg/kg, along with a trend to higher seizure burden however, a Cochrane review did not identify any adverse effects of higher-dose caffeine.
BabyCCINO will compare three dosing regimens routinely prescribed in Australia and Aotearoa New Zealand and assess health outcomes for infants who receive these.
Very preterm infants born \<32 weeks' gestation will be randomly assigned to receive either
* 40mg/kg loading dose and 20mg/kg daily maintenance
* 30 mg/kg loading dose and 15mg/kg daily maintenance, or
* 20mg/kg loading dose and 10mg/kg daily maintenance.
Health outcomes will be assessed using the PLATIPUS Ordinal Outcome Scale, at 42 weeks' postmenstrual age or discharge home, whichever is earliest.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 3900
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Caffeine citrate 40mg Caffeine citrate Dose and frequency 40mg/kg load and 20mg/kg maintenance daily, as long as clinically indicated. Administration Loading dose: 2mL/kg loading dose of study drug, either IV or enterally, administered at \<72 hours of life, followed by Maintenance dose: 1mL/kg maintenance dose given daily, either IV or enterally, commenced 24 hours after loading dose. Caffeine citrate 30mg Caffeine citrate Dose and frequency 30 mg/kg load and 15mg/kg maintenance daily, as long as clinically indicated. Administration Loading dose: 2mL/kg loading dose of study drug, either IV or enterally, administered at \<72 hours of life, followed by Maintenance dose: 1mL/kg maintenance dose given daily, either IV or enterally, commenced 24 hours after loading dose. Caffeine citrate 20mg Caffeine citrate Dose and frequency 20mg/kg load and 10mg/kg maintenance daily, as long as clinically indicated. Administration Loading dose: 2mL/kg loading dose of study drug, either IV or enterally, administered at \<72 hours of life, followed by Maintenance dose: 1mL/kg maintenance dose given daily, either IV or enterally, commenced 24 hours after loading dose.
- Primary Outcome Measures
Name Time Method Number of participants who progress by at least one level higher on the PLATIPUS Ordinal Outcome Scale At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier) The PLATIPUS-Ordinal Outcome Scale ranks the most severe core short-term infant health outcome in the specified time frame.
Levels 1-15: 1= Well, liveborn infant; 2= Neonatal unit admission for \<48 hours; 3= Neonatal unit admission for \>/= 48 hours; 4= Non-invasive respiratory support or oxygen therapy for ≥ 4 hours \& \< 5 days; 5= Non-invasive respiratory support or oxygen therapy \>/= 5 days; 6= Mechanical ventilation via endotracheal tube for ≥ 4 hours \& \<7 days; 7= Mechanical ventilation via endotracheal tube for \>/=7 days; 8= Moderate respiratory morbidity; 9=Necrotising enterocolitis AND/OR Sepsis; 10= Severe Respiratory Morbidity; 11= Major Surgery; 12= Brain Injury; 13= TWO of severe respiratory morbidity OR major surgery OR brain injury; 14= Severe respiratory morbidity \& major surgery \& brain injury; 15 = Death.
- Secondary Outcome Measures
Name Time Method Number of infants with moderate respiratory morbidity (as per the primary outcome) At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier). Number of infants meeting the PLATIPUS-Ordinal Outcome Scale definition of 'moderate respiratory morbidity'.
Number of infants with severe respiratory morbidity (as per the primary outcome) At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier). Number of infants meeting the PLATIPUS-Ordinal Outcome Scale definition of 'severe respiratory morbidity'.
Duration of any positive pressure ventilation, in days From first date and time (any mode), to final date and time (any mode), up to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier) Any positive pressure ventilation (mechanical ventilation, non-invasive positive pressure ventilation, continuous positive airway pressure or nasal high-flow therapy), in days (in survivors to 42 weeks' PMA or first discharge home from hospital, whichever is sooner).
Duration of mechanical ventilation, in days From start date and time, to end date and time, up to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier) Mechanical ventilation, in days (in survivors to 42 weeks' PMA or first discharge home from hospital, whichever is sooner).
Number of infants with patent ductus arteriosus treated with medication or surgery At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier) Number of infants with patent ductus arteriosus treated with medication or surgery.
Number of infants with retinopathy of prematurity receiving intraocular or laser treatment At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier) Number of infants with retinopathy of prematurity receiving intraocular or laser treatment.
Number of infants treated with postnatal systemic corticosteroids for preterm lung disease At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier) Number of infants treated with postnatal systemic corticosteroids for preterm lung disease.
Number of infants with presumed caffeine side-effects At any time prior to 42 weeks' postmenstrual age or first discharge home from hospital (whichever is earlier) Number of infants with presumed caffeine side-effects, where the treating clinician has reduced the dose or ceased caffeine.