Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial)

Jarinda A. Poppe, Robert B. Flint, Anne Smits, Sten P. Willemsen, Kelly K. Storm, Debbie H. Nuytemans, Wes Onland, Marten J. Poley, Willem P. de Boode, Katherine Carkeek, Vincent Cassart, Luc Cornette, Peter H. Dijk, Marieke A.C. Hemels, Isabelle Hermans, Matthias C. Hütten, Dorottya Kelen, Ellen H.M. de Kort, André A. Kroon, Julie LefevereKatleen Plaskie, Breanne Stewart, Michiel Voeten, Mirjam M. van Weissenbruch, Olivia Williams, Inge A. Zonnenberg, Thierry Lacaze-Masmonteil, Arjan B.te Pas, Irwin K.M. Reiss, Anton H. van Kaam, Karel Allegaert, G. Jeroen Hutten, Sinno H.P. Simons*

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    2 Citaten (Scopus)
    13 Downloads (Pure)

    Samenvatting

    Background: Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. 

    Methods: The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18–24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. 

    Discussion: Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. 

    Trial registration: ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020.

    Originele taal-2English
    Artikelnummer656
    Aantal pagina's13
    TijdschriftTrials
    Volume24
    Vroegere onlinedatum10-okt.-2023
    DOI's
    StatusPublished - 2023

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