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

Autor: Poppe JA; Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center Sophia Children's Hospital, Room Sk-4113, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands., Flint RB; Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center Sophia Children's Hospital, Room Sk-4113, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands.; Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands., Smits A; Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium.; Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Willemsen SP; Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands., Storm KK; Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center Sophia Children's Hospital, Room Sk-4113, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands., Nuytemans DH; Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, the Netherlands., Onland W; Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, the Netherlands.; Amsterdam Reproduction & Development, Amsterdam, the Netherlands., Poley MJ; Department of Paediatric Surgery and Intensive Care, Erasmus University Medical Center Sophia Children's Hospital, Rotterdam, the Netherlands.; Institute for Medical Technology Assessment (iMTA), Erasmus University Rotterdam, Rotterdam, the Netherlands., de Boode WP; Department of Neonatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Amalia Children's Hospital, Nijmegen, the Netherlands., Carkeek K; Neonatal Intensive Care Unit, Cliniques Universitaires Saint Luc, Brussels, Belgium., Cassart V; Department of Neonatology, Grand hôpital de Charleroi, Charleroi, Belgium., Cornette L; Department Neonatology, AZ St-Jan, Bruges, Belgium., Dijk PH; Division of Neonatology, Department of Paediatrics, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, the Netherlands., Hemels MAC; Department of Neonatology, Isala, Zwolle, Zwolle, the Netherlands., Hermans I; Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium., Hütten MC; Division of Neonatology, Department of Pediatrics, Maastricht University Medical Center, Maastricht, the Netherlands., Kelen D; Neonatal Department, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium., de Kort EHM; Division of Neonatology, Department of Pediatrics, Máxima Medical Center, Veldhoven, the Netherlands., Kroon AA; Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center Sophia Children's Hospital, Room Sk-4113, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands., Lefevere J; Neonatology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium., Plaskie K; Department of Neonatology, GasthuisZusters Antwerpen, Antwerp, Belgium., Stewart B; Quality Management in Clinical Research (QMCR), University of Alberta, Edmonton, AB, Canada., Voeten M; Department of Neonatal Intensive Care, University Hospital Antwerp, Edegem, Belgium., van Weissenbruch MM; Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, the Netherlands.; Amsterdam Reproduction & Development, Amsterdam, the Netherlands., Williams O; Neonatology and Neonatal Intensive Care Unit, CHIREC-Delta Hospital, Brussels, Belgium., Zonnenberg IA; Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands., Lacaze-Masmonteil T; Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Maternal Infant Child & Youth Research Network (MICYRN), Vancouver, Canada., Pas ABT; Division of Neonatology, Department of Paediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Centre, Leiden, the Netherlands., Reiss IKM; Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center Sophia Children's Hospital, Room Sk-4113, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands., van Kaam AH; Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, the Netherlands.; Amsterdam Reproduction & Development, Amsterdam, the Netherlands., Allegaert K; Department of Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, the Netherlands.; Department of Development and Regeneration, KU Leuven, Leuven, Belgium.; Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium., Hutten GJ; Department of Neonatology, Emma Children's Hospital, Amsterdam UMC, Amsterdam, the Netherlands.; Amsterdam Reproduction & Development, Amsterdam, the Netherlands., Simons SHP; Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus University Medical Center Sophia Children's Hospital, Room Sk-4113, Wytemaweg 80, 3015 CN, Rotterdam, the Netherlands. s.simons@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Trials [Trials] 2023 Oct 10; Vol. 24 (1), pp. 656. Date of Electronic Publication: 2023 Oct 10.
DOI: 10.1186/s13063-023-07683-5
Abstrakt: 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.
(© 2023. BioMed Central Ltd., part of Springer Nature.)
Databáze: MEDLINE
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