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.

Journal

The Lancet. Respiratory medicine

ISSN: 2213-2619

Titre abrégé: Lancet Respir Med

Pays: England

ID NLM: 101605555

Informations de publication

Date de publication:
18 Apr 2024

Historique:

received: 22 11 2023

revised: 21 02 2024

accepted: 26 02 2024

medline: 22 4 2024

pubmed: 22 4 2024

entrez: 21 4 2024

Statut: aheadofprint

Résumé

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. 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 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. 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. Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Sections du résumé

BACKGROUND BACKGROUND

METHODS 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

FINDINGS RESULTS

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 CONCLUSIONS

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 BACKGROUND

Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Identifiants

DOI: 10.1016/S2213-2600(24)00073-0 PMID: 38643780

pubmed: 38643780

pii: S2213-2600(24)00073-0

doi: 10.1016/S2213-2600(24)00073-0

pii:

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Investigateurs

Rahel Schuler (R)

Birgit Kampschulte (B)

Annesuse Schmidt (A)

Svilen Atanasov (S)

Mark Dzietko (M)

Sebastian Prager (S)

Ioana Bialas (I)

Petra Kramps (P)

Sarah Beckmann (S)

Jürgen Seidenberg (J)

Katja Majosthusmann (K)

Jenny Potratz (J)

Alijda van den Heuvel (A)

Maria Tekaat (M)

Susanne Dettmers (S)

Marie-Therese Unterweger (MT)

Heike Nowak (H)

Jens Möller (J)

Ulrich Thome (U)

Jörg Arand (J)

Beate Luger (B)

Christian A Maiwald (CA)

Martin Heideking (M)

Matthias Heckmann (M)

Annette Keller-Wacherbauer (A)

Holger Michel (H)

Tanja Karen (T)

Anna Schmid (A)

Yasmin Pellkofer (Y)

Elke Griesmaier (E)

Orsolya Genzel-Boroviczeny (O)

Raquel Mata Fernandez (R)

Stefan Avenarius (S)

Andrea Czoske (A)

Christoph Block (C)

Simone Schwarz (S)

Andreas Jenke (A)

Tamara Grass (T)

Martin Kuntz (M)

Fabian Fahlbusch (F)

Johannes Pöschl (J)

Jule Metzger (J)

Sebastian Ronellenfitsch (S)

Thomas Schaible (T)

Julia Reinhard (J)

Sonja Trepels-Kottek (S)

Jacqueline Bauer (J)

Egbert Herting (E)

Wolfram Henn (W)

Annette Laupert (A)

Rebecca Jathe (R)

Informations de copyright

Déclaration de conflit d'intérêts

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.