Samir Gupta1, Edmund Juszczak2,3, Pollyanna Hardy2,4, Nimish Subhedar5, Jonathan Wyllie6, Wilf Kelsall7, Sunil Sinha6, Sam Johnson8, Tracy Roberts4, Elisabeth Hutchison2, Justine Pepperell2, Louise Linsell2, Jennifer L Bell2, Kayleigh Stanbury2, Marketa Laube2, Clare Edwards2, David Field8. 1. University Hospital of North Tees, Hardwick Road, Stockton-On-Tees, TS19 8PE, UK. samir.gupta@durham.ac.uk. 2. National Perinatal Epidemiology Unit (NPEU) Clinical Trials Unit, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Headington, Oxford, OX3 7LF, UK. 3. Nottingham Clinical Trials Unit, School of Medicine, University of Nottingham, University Park Nottingham, Nottingham, NG7 2RD, UK. 4. Institute of Applied Health Research, University of Birmingham, Birmingham, B15 2TT, UK. 5. Liverpool Women's NHS Foundation Trust, Crown Street, Liverpool, L8 7SS, UK. 6. South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough, TS4 3BW, UK. 7. NICU, Rosie Hospital, Cambridge University Hospital Foundation Trust, Cambridge, CB2 2QQ, UK. 8. The University of Leicester, Department of Health Science, University Road, George Davies Centre, Leicester, LE1 7RH, UK.
Abstract
BACKGROUND: The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks' gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic. METHODS: This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23+ 0-28+ 6 weeks' gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23+ 0-28+ 6 weeks' gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks' postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. DISCUSSION: Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done. Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks' postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age. TRIAL REGISTRATION: ISRCTN84264977 . Date assigned: 15/09/2010.
RCT Entities:
BACKGROUND: The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks' gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic. METHODS: This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23+ 0-28+ 6 weeks' gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23+ 0-28+ 6 weeks' gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks' postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. DISCUSSION: Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done. Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks' postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age. TRIAL REGISTRATION: ISRCTN84264977 . Date assigned: 15/09/2010.
Authors: Sheri L Nemerofsky; Elvira Parravicini; David Bateman; Charles Kleinman; Richard A Polin; John M Lorenz Journal: Am J Perinatol Date: 2008-10-10 Impact factor: 1.862
Authors: Samir Gupta; Edmund Juszczak; Pollyanna Hardy; Nimish Subhedar; Jonathan Wyllie; Wilf Kelsall; Sunil Sinha; Sam Johnson; Tracy Roberts; Elisabeth Hutchison; Justine Pepperell; Louise Linsell; Jennifer L Bell; Kayleigh Stanbury; Marketa Laube; Clare Edwards; David Field Journal: BMC Pediatr Date: 2021-07-27 Impact factor: 2.125