Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
25 Jan 2024
Historique:
medline: 24 1 2024
pubmed: 24 1 2024
entrez: 24 1 2024
Statut: ppublish

Résumé

The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

Sections du résumé

BACKGROUND BACKGROUND
The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known.
METHODS METHODS
We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age.
RESULTS RESULTS
A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen.
CONCLUSIONS CONCLUSIONS
The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

Identifiants

DOI: 10.1056/NEJMoa2305582 PMID: 38265644
pubmed: 38265644
doi: 10.1056/NEJMoa2305582
doi:

Banques de données

ISRCTN
['ISRCTN84264977']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

314-325

Subventions

Organisme : Health Technology Assessment Programme
ID : HTA Project: 11/92/15

Investigateurs

Saulius Satas (S)
Margaret Connon (M)
Stephen Main (S)
Susan MacFarlane (S)
Anthony Wilfred Ross Kelsall (AW)
Katherine Bradly Russell (K)
Helen Shelley (H)
Beth Berthlecon (B)
Sajeev Job (S)
Anand Kamalanathan (A)
Sharon Hughes (S)
Lucy Lewis (L)
Aung Soe (A)
Jaideep Singh (J)
Eve Irvine (E)
Katie Price (K)
Laura Thrasyvoulou (L)
Juneka Begum (J)
Jacqueline Daglish (J)
Vishna Rasiah (V)
Anju Singh (A)
Rachel Jackson (R)
Efygenia Kotsia (E)
Amy Woodhead (A)
Abby Twiss (A)
Maxine Heather Barrow (MH)
Elizabeth Simcox (E)
Sam Wallis (S)
Rachel Wane (R)
Savithiri Sivashankar (S)
Emily Andrews (E)
Heather Collier (H)
Chi-Ning Gerrard (CN)
Caroline Cowman (C)
Bev Hammond (B)
Frances Pickering (F)
Robert John Madar (RJ)
Sarah-Jane Sharman (SJ)
Alison Stolton (A)
Jonathan Wyllie (J)
Caroline Buckley (C)
Amanda Forster (A)
Helena Smith (H)
Suzanne Bell (S)
Porus Bustani (P)
Pauline Bayliss (P)
Rachel Sellars (R)
Lynne Smart (L)
Liz Taylor (L)
Beth Lally (B)
Lawrence Miall (L)
Nicola Balatoni (N)
Suzanne Laing (S)
Collette Spencer (C)
Sarah Thornton (S)
Lindsay Uryn (L)
Laura Dalton (L)
Katherine Pettinger (K)
Charlotte Reilly (C)
Jonathan Cusack (J)
Marie Hubbard (M)
Rosalind Astles (R)
Maria Sharpe (M)
Jennifer Smith (J)
Nimish Subhedar (N)
Karen Harvey (K)
Joanne Windrow (J)
Patrick McGowan (P)
Amy Beasley (A)
Sateeshkumar Somisetty (S)
Yvonne Millar (Y)
Olaitan Adesiyan (O)
Jenny Baker (J)
Santosh Pattnayak (S)
Helen Harizaj (H)
Aimee Harris (A)
Sarah Jones (S)
Alison Youdale (A)
Rahul Roy (R)
Samantha Claire (S)
Supriya Bhoomaiah (S)
Karen Few (K)
Katherine Lloyd (K)
Amy Nichols (A)
Laura Playne (L)
Jay Banerjee (J)
Batia Gourin (B)
Zoe McClure (Z)
Kirupalini Mariampillai (K)
Sundar Satyamurthy (S)
Christopher Kissack (C)
Sally Yip (S)
Lynn Clark (L)
Bharathi Rao (B)
Eileen Killen (E)
Jennifer McGowan (J)
Muriel Millar (M)
Mary O'Neill (M)
Angela Abbate (A)
Rachel Anderson (R)
Julie Brown (J)
Patrick Lawlor (P)
Judith Ratcliffe (J)
Eileen Rogers (E)
Akaolisa Egbeama (A)
Joanna Lees (J)
Claire Lodge (C)
Natalie Morgan (N)
Raju Narasimhan (R)
Paula Sugden (P)
Sundeep Harigopal (S)
Julie Groombridge (J)
Tracey Downes (T)
Donovan Duffy (D)
Naomi Hayward (N)
Anay Kulkarni (A)
Izabela Andrzejewska (I)
Vania Oliveira (V)
Sundar Sathiyamurthy (S)
Arindam Mukherjee (A)
Nicola Booth (N)
Karen Dockery (K)
Clare Jennings (C)
Louise Weaver-Lowe (L)
Katherine Birchall (K)
Majid Abu-Harb (M)
Natalie Talbot (N)
Paul Corrigan (P)
Siddhartha Sen (S)
Alison Davies (A)
Angela Harris (A)
Ajay Sinha (A)
MaySze Chang (M)
Caroline Francia (C)
Ivone Lancoma-Malcolm (I)
Gail Falder (G)
Rainer Ebel (R)
Mrinalini Rajimwale (M)
Francesca Brewer (F)
Rebecca Grenfell (R)
Nicola Watts (N)
Laura Wild (L)
Nicolas Aldridge (N)
Susan Dale (S)
Jo Gmerek (J)
Kerri McGowan (K)
Samir Gupta (S)
Sundaram Janakiraman (S)
Alex Ramshaw (A)
Wendy Cheadle (W)
Chidambara Harikumar (C)
Nazakat Merchant (N)
Shabana Malik (S)
Suminthra Naidu (S)
Rona Verdadero (R)
Amit Gupta (A)
Shermi George (S)
Claire Moloney (C)
Vimal Vasu (V)
Gopala Krishnan (G)
Denise Vigni (D)
Jennifer Bell (J)
Ursula Bowler (U)
Christina Cole (C)
Kerrianne Dempster (K)
Clare Edwards (C)
Pollyanna Hardy (P)
Nina Jamieson (N)
Edmund Juszczak (E)
Ann Kennedy (A)
Andy King (A)
Marketa Laube (M)
Louise Linsell (L)
David Murray (D)
Heather O'Connor (H)
Charles Roehr (C)
Kayleigh Stanbury (K)
Julia Sutton (J)
Joy Wiles (J)
Tracey Roberts (T)
Chidubem Okeke Ogwulu (CO)
Jane Greenaway (J)
Pauline Shephard (P)
Volker Straub (V)
Justin Carter (J)
Ben Snook (B)
Denis Azzopardi (D)
Michael Weindling (M)
Narender Aladangady (N)
Sophie Welch (S)
Tim Clayton (T)
Alan Montgomery (A)
David Edwards (D)
Heike Rabe (H)

Informations de copyright

Copyright © 2024 Massachusetts Medical Society.

Auteurs

Samir Gupta (S)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Nimish V Subhedar (NV)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Jennifer L Bell (JL)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

David Field (D)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Ursula Bowler (U)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Elizabeth Hutchison (E)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Sam Johnson (S)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Wilf Kelsall (W)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Justine Pepperell (J)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Tracy Roberts (T)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Sunil Sinha (S)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Kayleigh Stanbury (K)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Jonathan Wyllie (J)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Pollyanna Hardy (P)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Edmund Juszczak (E)

From the Division of Neonatology, Sidra Medicine, Doha, Qatar (S.G.); and the Department of Engineering, Durham University, Durham (S.G.), Liverpool Women's NHS Foundation Trust, Liverpool (N.V.S.), the National Perinatal Epidemiology Unit Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Oxford (J.L.B., U.B., E.H., J.P., K.S., P.H.), the Department of Health Science University of Leicester, George Davies Centre, Leicester (D.F., S.J.), NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge (W.K.), the Institute of Applied Health Research, University of Birmingham, Birmingham (T.R.), South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (S.S., J.W.), and the School of Medicine, University of Nottingham, Nottingham (E.J.) - all in the United Kingdom.

Classifications MeSH