Doxapram Therapy in Preterm Infants (DOXA Trial)

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age23-29
SponsorErasmus Medical Center

About this trial

Preterm infants often suffer from apnea of prematurity (AOP; a cessation of breathing) due to immaturity of the respiratory system. AOP can lead to oxygen shortage and a low heart rate which might harm the development of the newborn, especially the central nervous system. In order to prevent oxygen shortage, infants are treated with non-invasive respiratory support and caffeine. Despite these treatments, many preterm newborns still suffer from AOP and need invasive mechanical ventilation. Although this will result in complete resolution of AOP, invasive mechanical ventilation has the disadvantage of being a major risk of chronic lung disease and impaired neurodevelopmental outcome. Restrictive invasive ventilation is therefore advocated nowadays in preterm infants. Doxapram is a respiratory stimulant that has been administered off-label to treat AOP. Doxapram, as add-on treatment, seems to be effective in treating AOP and to prevent invasive mechanical ventilation. It is unclear if a preterm infant benefit from doxapram treatment on the longer term. This study compares doxapram to placebo and hypothesizes that doxapram will protect preterm infants from both invasive ventilation (and related lung disease) and AOP related oxygen shortage (and related impaired brain development).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Admitted to the neonatal intensvie care unit (NICU) of one of the participating centres

Written informed consent of both parents or legal representatives

Gestational age at birth < 29 weeks

Caffeine therapy, adequately dosed (see also under co-medication)

Disqualifiers

Previous use of open label doxapram

Use of theophylline (to replace doxapram)

Chromosomal defects (e.g. trisomy 13, 18, or 21)

Major congenital malformations that: compromise lung function (e.g. surfactant protein deficiencies, congenital diaphragmatic hernia); result in chronic ventilation (e.g. Pierre Robin sequence); increase the risk of death or adverse neurodevelopmental outcome (congenital cerebral malformations, chromosomal abnormalities);

Trial design

Design model

Parallel

Treatments tested in this trial

  • Doxapram

    Drug

    Loading dose and continuous doxapram infusion.

  • Placebo

    Drug

    Loading dose and continuous placebo infusion.

Treatment groups

396 Participants
are divided into 2 treatment groups
Group A: DoxapramExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Death or severe disability

Disability will be defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness. Cognitive delay will be defined as a Mental Development Index score of less than 85 on the Bayley Scales of Infant and Toddler Development, Bayley Score of Infant Development (BSID) III scores. Cerebral palsy will be diagnosed if the child had a non-progressive motor impairment characterized by abnormal muscle tone and decreased range or control of movements. The level of gross motor function will be determined with the use of the Gross Motor Function Classification System. Audiometry will be performed to determine the presence or absence of hearing loss. Blindness will be defined as a corrected visual acuity less than 20/200

Time frame
2 years corrected age

Secondary outcomes

1

Broncho pulmonary dysplasia

Diagnosed according to the National Institute of Child Health and Human Development (NICHD) criteria

Time frame
36 weeks post menstrual age
2

Death

Death at 36 weeks post menstrual age and hospital mortality

Time frame
until 36 weeks post menstrual age and until hospital discharge
3

Admission period

Length of stay at the intensive care, length of stay in hospital

Time frame
through study completion and until discharge home, average 3 months
4

Endotracheal intubations

Incidence of endotracheal intubations

Time frame
Day 3, 7, 14, and 21 after start of study medication

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Erasmus Medical Center

Lead sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Collaborator

Nederlands Neonataal Netwerk (N3), the Netherlands

Collaborator

Universitaire Ziekenhuizen KU Leuven

Collaborator

Maternal, Infant, Child and Youth Research Network (MICYRN)

Collaborator