Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial
| Autor: | Olivier, Baud, Laure, Maury, Florence, Lebail, Duksha, Ramful, Fatima, El Moussawi, Claire, Nicaise, Véronique, Zupan-Simunek, Anne, Coursol, Alain, Beuchée, Pascal, Bolot, Pierre, Andrini, Damir, Mohamed, Corinne, Alberti, Annick, Tibi |
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| Přispěvatelé: | Réanimation et Pédiatrie Néonatales, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 ( UPD7 ) -IFR2-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital de Corbeil-ESsonnes, Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), Centre Hospitalier de Poissy Saint-Germain (CHIPS), centre hospitalier universitaire, hôpital Nord, Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP), Médecine Néonatale et Réanimation Pédiatrique, CH René Dubos, Centre Hospitalier Universitaire de Rennes, Néonatalogie, Centre Hospitalier de Saint-Denis, CHU Grenoble, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables ( Inserm U1123 - ECEVE ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire [Rennes], Centre Hospitalier de Saint-Denis [Ile-de-France], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Universités-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris]-Université Paris Diderot - Paris 7 (UPD7) |
| Rok vydání: | 2016 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Hydrocortisone [SDV]Life Sciences [q-bio] Anti-Inflammatory Agents/administration & dosage Anti-Inflammatory Agents Placebo Hydrocortisone/administration & dosage/analogs & derivatives law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial Double-Blind Method law 030225 pediatrics Intensive care Medicine Humans 030212 general & internal medicine Bronchopulmonary Dysplasia/prevention & control Bronchopulmonary Dysplasia Intention-to-treat analysis ddc:618 [ SDV ] Life Sciences [q-bio] business.industry Postmenstrual Age Infant Newborn Gestational age General Medicine medicine.disease 3. Good health Logistic Models Treatment Outcome Bronchopulmonary dysplasia Infant Extremely Premature Gestation Female France business |
| Zdroj: | The Lancet, Vol. 387, No 10030 (2016) pp. 1827-1836 Lancet Lancet, Elsevier, 2016, 〈10.1016/S0140-6736(16)00202-6〉 The Lancet The Lancet, 2016, ⟨10.1016/S0140-6736(16)00202-6⟩ Lancet, Elsevier, 2016, ⟨10.1016/S0140-6736(16)00202-6⟩ |
| ISSN: | 1474-547X 0140-6736 |
| DOI: | 10.1016/S0140-6736(16)00202-6〉 |
| Popis: | International audience; SummaryBackground Bronchopulmonary dysplasia, a major complication of extreme prematurity, has few treatment options. Postnatal steroid use is controversial, but low-dose hydrocortisone might prevent the harmful effects of inflammation on the developing lung. In this study, we aimed to assess whether low-dose hydrocortisone improved survival without bronchopulmonary dysplasia in extremely preterm infants. Methods In this double-blind, placebo-controlled, randomised trial done at 21 French tertiary-care neonatal intensive care units (NICUs), we randomly assigned (1:1), via a secure study website, extremely preterm infants inborn (born in a maternity ward at the same site as the NICU) at less than 28 weeks of gestation to receive either intravenous low-dose hydrocortisone or placebo during the first 10 postnatal days. Infants randomly assigned to the hydrocortisone group received 1 mg/kg of hydrocortisone hemisuccinate per day divided into two doses per day for 7 days, followed by one dose of 0·5 mg/kg per day for 3 days. Randomisation was stratified by gestational age and all infants were enrolled by 24 h after birth. Study investigators, parents, and patients were masked to treatment allocation. The primary outcome was survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age. We used a sequential analytical design, based on intention to treat, to avoid prolonging the trial after either efficacy or futility had been established. This trial is registered with ClinicalTrial.gov, number NCT00623740. Findings 1072 neonates were screened between May 25, 2008, and Jan 31, 2014, of which 523 were randomly assigned (256 hydrocortisone, 267 placebo). 255 infants on hydrocortisone and 266 on placebo were included in analyses after parents withdrew consent for one child in each group. Of the 255 infants assigned to hydrocortisone, 153 (60%) survived without bronchopulmonary dysplasia, compared with 136 (51%) of 266 infants assigned to placebo (odds ratio [OR] adjusted for gestational age group and interim analyses 1·48, 95% CI 1·02–2·16, p=0·04). The number of patients needed to treat to gain one bronchopulmonary dysplasia-free survival was 12 (95% CI 6–200). Sepsis rate was not significantly different in the study population as a whole, but subgroup analyses showed a higher rate only in infants born at 24–25 weeks gestational age who were treated with hydrocortisone (30 [40%] of 83 vs 21 [23%] of 90 infants; sub-hazard ratio 1·87, 95% CI 1·09–3·21, p=0·02). Other potential adverse events, including notably gastrointestinal perforation, did not differ significantly between groups. Interpretation In extremely preterm infants, the rate of survival without bronchopulmonary dysplasia at 36 weeks of postmenstrual age was significantly increased by prophylactic low-dose hydrocortisone. This strategy, based on a physiological rationale, could lead to substantial improvements in the management of the most premature neonates. Funding Assistance Publique-Hôpitaux de Paris |
| Databáze: | OpenAIRE |
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