Preterm birth is the most common cause of neonatal death and related to important long term morbidity. Invasive mechanical ventilation is often needed after preterm birth because of underdeveloped lungs and breathing center, but is related to impaired outcome. Today, invasive mechanical ventilation is therefore minimized in preterm infants.
The newborns' own breathing is supported with non-invasive support with air and oxygen, and the breathing is stimulated with caffeine treatment. Unfortunately, apnea and oxygen desaturations often remain in these very preterm infants. The desaturations and fluctuations in oxygen potentially affect the brain and its development.
Treatment with doxapram provides a high potential solution in addition to standard of care for these infants. Doxapram is increasingly used off-label in our neonatal intensive care units. Our previous observational and PK/PD studies provided the necessary data the potential short term effects and about the optimal doxapram dosing in preterm newborns. High quality research on efficacy and safety on the long term perspective of doxapram is however missing, but urgently needed. It has been given highest priority by the Dutch neonatal research network and is highly supported by clinicians and the parents of preterm infants.
We will perform a unique multicenter double blinded randomized placebo controlled trial to determine if doxapram is able to protect newborns on the long term perspective. Outcome (survival without severe disability) at the age of 2 years will be compared in a total number of 356 preterm infants born before 29 weeks of gestation. Next to short term benefits, we will also study the outcome after 5.5 and 8 years, enabling us to also determine effects on IQ, quality of life, health gain and cost effectiveness. In this way our consortium will be able to provide the highly needed knowledge about doxapram that will be implemented into (inter)national guidelines afterwards.