Doxapram for Apnoea of Prematurity (DoxAPrem) Dosage Study

The aim of this study is to evaluate use of doxapram by the oral route for treatment of apnoea in very preterm infants (pauses in breathing with desaturation and/or bradycardia). Apnoea occurs in approximately 70% of infants born at 32 weeks' gestation and is associated with delayed feeding, increased mortality and increased risk of neurodevelopmental impairment and long-term respiratory morbidity. First line treatment of apnoea involves continuous positive airway pressure (CPAP) and caffeine treatment. Infants who are refractory to caffeine are usually trialled on doxapram, an alternative respiratory stimulant. Traditionally doxapram has been given by continuous intravenous infusion, but long-term intravenous access can be difficult to maintain and increases the risk of sepsis. Several studies have found that oral doxapram is equally effective but the optimal oral dose in preterm infants is unclear. This trial will compare two oral doses of doxapram (12 mg/kg vs. 24 mg/kg 6 hourly) to determine which is more likely to achieve therapeutic blood concentrations. Plasma concentrations will also be used to develop a pharmacokinetic model to optimise dosing based on gestation and postnatal age. Effect of oral doxapram on respiratory parameters and tolerance will also be assessed.