Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

Autor:	Meyer S; Clinical Centre Karlsruhe, Franz-Lust Clinic for Paediatrics, Karlsruhe, Germany. Electronic address: sascha.meyer@klinikum-karlsruhe.de., Bay J; University Hospital Homburg, Saarland University Medical Center, Clinic for Paediatrics and Neonatology, Homburg, Germany., Franz AR; University Hospital Tübingen, Neonatology and Center for Paediatric Clinical Studies, Department for Paediatrics, Tübingen, Germany., Ehrhardt H; Department of Paediatrics and Adolescent Medicine, Division of Neonatology and Pediatric Intensive Care Medicine, University Medical Center Ulm, Ulm, Germany., Klein L; Department of General Paediatrics and Neonatology, Justus-Liebig-Universität, Giessen, Germany., Petzinger J; Department of General Paediatrics and Neonatology, Justus-Liebig-Universität, Giessen, Germany., Binder C; Medical University Wien, Center of Paediatrics, Department of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Vienna, Austria., Kirschenhofer S; Medical University Wien, Center of Paediatrics, Department of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Vienna, Austria., Stein A; University Hospital Essen, Clinic for Paediatrics I, Department for Neonatology, Essen, Germany., Hüning B; University Hospital Essen, Clinic for Paediatrics I, Department for Neonatology, Essen, Germany., Heep A; Clinical Centre Oldenburg, Clinic for Neonatology, Paediatric Intensive Care, Paediatric Cardiology, Paediatric Pneumonology and Allergology, Oldenburg, Germany., Cloppenburg E; Clinical Centre Oldenburg, Clinic for Neonatology, Paediatric Intensive Care, Paediatric Cardiology, Paediatric Pneumonology and Allergology, Oldenburg, Germany., Muyimbwa J; Clinical Centre Oldenburg, Clinic for Neonatology, Paediatric Intensive Care, Paediatric Cardiology, Paediatric Pneumonology and Allergology, Oldenburg, Germany., Ott T; University Hospital Münster, Clinic for Paediatrics, Department for Neonatology, Münster, Germany., Sandkötter J; University Hospital Münster, Clinic for Paediatrics, Department for Neonatology, Münster, Germany., Teig N; University Hospital Bochum, Children's Hospital-St Josef-Hospital, Department for Neonatology and Paediatric Intensive Care, Bochum, Germany., Wiegand S; University Hospital Bochum, Children's Hospital-St Josef-Hospital, Department for Neonatology and Paediatric Intensive Care, Bochum, Germany., Schroth M; Cnopf'sche Kinderklinik, Clinic for Neonatology and Paediatric Intensive Care, Nürnberg, Germany., Kick A; Cnopf'sche Kinderklinik, Clinic for Neonatology and Paediatric Intensive Care, Nürnberg, Germany., Wurm D; Clinical Centre Saarbrücken, Clinic for Paediatrics, Saarbrücken, Germany., Gebauer C; University Hospital Leipzig, Center of Paediatrics, Department for Neonatology, Leipzig, Germany., Linnemann K; University Hospital Greifswald, Center for Paediatrics, Department for Neonatology and Paediatric Intensive Care, Greifswald, Germany., Kittel J; Barmherzige Brüder Hospital Regensburg, Clinic St Hedwig, Clinic for Paediatrics, Regensburg, Germany., Wieg C; Clinical Centre Aschaffenburg-Alzenau, Clinic for Paediatrics, Department for Neonatology and Paediatric Intensive Care, Aschaffenburg, Germany., Kiechl-Kohlendorfer U; University Hospital Innsbruck, Clinic for Paediatrics II/Neonatology, Innsbruck, Austria., Schmidt S; LMU Clinic for Paediatrics, Haunersches Kinderspital, Munich, Germany., Böttger R; University Hospital Magdeburg, Clinic for Paediatrics, Magdeburg, Germany., Thomas W; Hospital Mutterhaus der Borromäerinnen, Clinic for Paediatrics, Trier, Germany., Brevis Nunez F; Sana Hospital Duisburg, Clinic for Paediatrics, Department of Paediatric Intensive Care, Duisburg, Germany., Stockmann A; Evangelical Hospital Oberhausen, Center of Paediatrics, Department of Neonatology, Oberhausen, Germany., Kriebel T; Westpfalz-Klinikum Kaiserslautern, Department of Paediatrics, Kaiserslautern, Germany., Müller A; University Hospital Bonn, Eltern-Kind-Zentrum (ELKI), Neonatology/Paediatric Intensive Care, Bonn, Germany., Klotz D; University Hospital Freiburg, Centre for Paediatrics, Department for Neonatology and Paediatric Intensive Care, Freiburg, Germany., Morhart P; Center of Paediatrics, Department for Neonatology and Paediatric Intensive Care, Erlangen, Germany., Nohr D; University Hohenheim, Stuttgart, Germany., Biesalski HK; University Hohenheim, Stuttgart, Germany., Giannopoulou EZ; University Hospital Ulm, Clinic for Paediatrics, Paediatric Endocrinology and Diabetology, Ulm, Germany., Hilt S; University Hospital Homburg, Saarland University Medical Center, Clinic for Paediatrics and Neonatology, Homburg, Germany., Poryo M; University Hospital Homburg, Saarland University Medical Center, Clinic for Paediatric Cardiology, Homburg, Germany., Wagenpfeil S; University Hospital Homburg, Saarland University Medical Center, Clinic for Paediatrics and Neonatology, Homburg, Germany., Haiden N; Medical University Wien, Center of Paediatrics, Department of Neonatology, Paediatric Intensive Care and Neuropaediatrics, Vienna, Austria., Ruckes C; Interdisziplinäres Zentrum Klinische Studien (IZKS), Universitätsmedizin Johannes Gutenberg-University Mainz, Mainz, Germany., Ehrlich A; Interdisziplinäres Zentrum Klinische Studien (IZKS), Universitätsmedizin Johannes Gutenberg-University Mainz, Mainz, Germany., Gortner L; University Hospital Homburg, Saarland University Medical Center, Clinic for Paediatrics and Neonatology, Homburg, Germany.
Jazyk:	angličtina
Zdroj:	The Lancet. Respiratory medicine [Lancet Respir Med] 2024 Jul; Vol. 12 (7), pp. 544-555. Date of Electronic Publication: 2024 Apr 18.
DOI:	10.1016/S2213-2600(24)00073-0
Abstrakt:	Background: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. Methods: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32 +0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. Findings: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. Interpretation: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. Funding: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN). Competing Interests: Declaration of interests We declare no competing interests. The vitamin A study medication and placebo were provided by Aristo Pharma, Berlin, Germany. Aristo Pharma had no influence on study protocol, data compilation, and data analysis. (Copyright © 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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