None listed
Conditions
Brief summary
Late preterm infants (34+0-36+6 weeks’ gestational age (GA)) are the most common of all preterm infants, constituting 6% of all births or 3,700 births annually in New Zealand. These infants have a 30% increased risk of severe long-term neurodevelopmental impairment compared to infants born at term. While there has been progress in improving neurodevelopmental outcomes for infants born more preterm, it is only recently that late preterm infants have been recognised as being at risk of significant problems. Remarkably, there has been very little research on how to improve the long term outcomes of infants born late preterm. We propose the Latte Dosage Trial, a randomised, placebo-controlled dosage trial of oral caffeine citrate from birth to term equivalent age to reduce intermittent hypoxaemia in late preterm infants.
Interventions
Infants will be randomised to a caffeine citrate dose of 5 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg or placebo (water), with 1:1:1:1:1 allocation. Infants will be randomised within 72 hours of birth. Infants from multiple births will be randomised to the same treatment group.
Randomised infants will receive a study allocation letter (A to E) that corresponds to pre-labelled study bottles containing either caffeine or placebo (identical appearanec). To maintain blinding all infants will receive the
Infants will be randomised to a caffeine citrate dose of 5 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg or placebo (water), with 1:1:1:1:1 allocation. Infants will be randomised within 72 hours of birth. Infants from multiple births will be randomised to the same treatment group. Randomised infants will receive a study allocation letter (A to E) that corresponds to pre-labelled study bottles containing either caffeine or placebo (identical appearanec). To maintain blinding all infants will receive the same dose volume (1ml/kg, once daily) of their allocated caffeine concentration. Infants will be given a 2 ml/kg enteral loading dose of the study drug (10 mg/kg, 20 mg/kg, 30 mg/kg or 40 mg/kg of caffeine citrate or water) at 7-9 am on the first morning after the infant reaches 72 hours of age, followed by a daily dose of 1 ml/kg each morning (5 mg/kg, 10mg/kg, 15 mg/kg or 20 mg/kg of caffeine citrate or placebo) until term equivalent age (40 weeks’ post-menstrual age). The dose will be recalculated for the infants’ weight gain weekly after the infant has regained birth weight. The study drug is given via a nasogastric tube for infants with a tube in situ, and orally for infants who do not require a nasogastric tube. Infants who are not able to tolerate enteral medications will have the study drug withheld. Adherence will be assessed by a drug dairy which details the volume of the study drug that was given, the time of the dose, and any vomiting or reflux with the medication. This will be checked by the research nurse at the two weeks visit and collected at the last visit. At the two weeks visit the research nurse will give the parents a new bottle of the study drug and collect the current bottle to measure compliance. On the last visit (term equivalent age) the research nurse will ask what treatment they thought their infant received, to assess the adequacy of study blinding, and collect the remaining study drug for measurement to determine the remaining volume. Good compliance will be defined as <20% of the expected study drug volume remaining or missing <20% of daily doses by term equivalent age.
Sponsors
The University of Auckland
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
0 to 50 Years
Healthy volunteers
No
Inclusion criteria
Infants: Infants born between 34+0 – 36+6 weeks’ GA without contradiction to caffeine treatment and are 72 hours of age or less. Mothers: Mother's who have given birth to an infant who is of 34+0 - 36+6 GA
Exclusion criteria
Infants: • Major congenital abnormality • Minor congenital abnormality likely to affect respiration, growth or development • Previous caffeine treatment • Renal or hepatic impairment • Tachyarrhythmia • Seizures • Hypoxic ischaemic encephalopathy • Residing outside of the Auckland DHB regions Mothers: Mother's who have given birth to an infant who has any of the exclusion criteria listed above
Outcome results
None listed