Background. In recent years, particular attention has been paid to all interventions that
could help reduce the need for mechanical ventilation MV and, therefore, the risk of BPD.
However, early application of non-invasive respiratory supports and early treatment with
surfactant fail in 45-50% of cases. Failure frequently depends on the onset of apnea episodes
and, therefore, it has been proposed to treat very preterm infants with caffeine already in
the delivery room in the first min of life.
Hypothesis and objectives of the study. Our aim is to verify the hypothesis that it is
possible to administer caffeine in the delivery room intravenously and enterally via an
orogastric tube.
Study design. Infants 25-29 weeks of gestational age will be enrolled and will be randomized
to receive 20 mg/kg of caffeine citrate intravenously, via the umbilical vein, or enterally,
through an orogastric tube, within 10 min of birth. The dosage of plasma caffeine
concentration will be performed 60+15 min after administration to measure its peak and 60+15
min before the next dose (5 mg/kg/day i.v.).
Endpoints. The primary endpoint will be the evaluation of the success rate of intravenous or
enteral administration of caffeine in the delivery room. Secondary endpoints will be the
evaluation of: number of infants in whom caffeine will be successfully administered by
intravenous versus enteral route; number of infants where caffeine will be successfully
administered that reached the therapeutic plasmatic range the first dose, confirming the
success of the administration; comparison of caffeine blood level obtained with intravenous
and enteral administration; frequency of successes in obtaining the therapeutic range after
the second dose; frequency of MV within the first 72 hours of life in studied infants.
Statistical analysis. In the absence of previous studies to use as a reference and this study
being a feasibility study, it was decided arbitrarily to study 20 infants treated in the
delivery room with caffeine administered intravenously and 20 infants treated in the delivery
room with caffeine administered enterally. The clinical characteristics of the two groups
will be described by calculating the mean value and the standard deviation or the rate and
percentage. The primary endpoint will be evaluated by calculating the percentage of cases in
which caffeine will be successfully administered. The comparison between the number of
infants in which caffeine will be successfully administered intravenously versus the enteral
route and the comparison between the caffeine plasma level obtained with intravenous and
enteral administration will be performed using the Student "t" test for continuous parametric
variables, the Wilcoxon rank sum test for non-parametric continuous variables and the χ2 test
for categorical variables. A p <0.05 will be considered as statistically significant.