Peter A Dargaville1,2, C Omar F Kamlin3,4, Francesca Orsini5, Xiaofang Wang5, Antonio G De Paoli2, H Gozde Kanmaz Kutman6, Merih Cetinkaya7, Lilijana Kornhauser-Cerar8, Matthew Derrick9, Hilal Özkan10, Christian V Hulzebos11, Georg M Schmölzer12, Ajit Aiyappan13, Brigitte Lemyre14, Sheree Kuo15, Victor S Rajadurai16, Joyce O'Shea17, Manoj Biniwale18, Rangasamy Ramanathan18, Alla Kushnir19, David Bader20, Mark R Thomas21, Mallinath Chakraborty22, Mariam J Buksh23, Risha Bhatia24, Carol L Sullivan25, Eric S Shinwell26, Amanda Dyson27, David P Barker28, Amir Kugelman29, Tim J Donovan30, Markus K Tauscher31, Vadivelam Murthy32, Sanoj K M Ali33, Pete Yossuck34, Howard W Clark35,36, Roger F Soll37, John B Carlin5,38, Peter G Davis3,4. 1. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia. 2. Department of Paediatrics, Royal Hobart Hospital, Hobart, Australia. 3. Neonatal Services, Royal Women's Hospital, Melbourne, Australia. 4. Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia. 5. Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Melbourne, Australia. 6. Department of Neonatology, Zekai Tahir Burak Maternity Teaching Hospital, Ankara, Turkey. 7. Division of Neonatology, Department of Pediatrics, Istanbul Kanuni Sultan Süleyman Training and Research Hospital, Istanbul, Turkey. 8. Department of Perinatology, Division of Gynaecology and Obstetrics, University Medical Centre, Ljubljana, Slovenia. 9. Division of Neonatology, NorthShore University Health System, Evanston, Illinois. 10. Department of Pediatrics, Division of Neonatology, Uludağ University Faculty of Medicine, Bursa, Turkey. 11. Division of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, the Netherlands. 12. Division of Neonatology, Department of Pediatrics, University of Alberta, Edmonton, Canada. 13. Neonatal Services, Mercy Hospital for Women, Heidelberg, Australia. 14. Department of Obstetrics, Gynecology, and Newborn Care, Ottawa Hospital, Ottawa, Ontario, Canada. 15. Department of Pediatrics, Kapi'olani Medical Center for Women and Children, Honolulu, Hawaii. 16. Department of Neonatology, KK Women's and Children's Hospital, Duke-NUS Medical School, Singapore. 17. Neonatal Unit, Royal Hospital for Children, Glasgow, Scotland. 18. Division of Neonatology, Department of Pediatrics, LAC+USC Medical Center and Good Samaritan Hospital, Keck School of Medicine of USC, Los Angeles, California. 19. Department of Pediatrics, Children's Regional Hospital, Cooper University Health Care, Camden, New Jersey. 20. Department of Neonatology, Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 21. Department of Neonatal Medicine, Chelsea and Westminster Hospital NHS Foundation Trust, London, England. 22. Regional Neonatal Intensive Care Unit, University Hospital of Wales, Cardiff. 23. Newborn Service, Starship Child Health, Auckland Hospital, Auckland, New Zealand. 24. Monash Newborn, Monash Children's Hospital, Clayton, Australia. 25. Department of Neonatology, Singleton Hospital, Swansea, Wales. 26. Department of Neonatology, Ziv Medical Center, Faculty of Medicine, Bar-Ilan University, Tsfat, Israel. 27. Department of Neonatology, Centenary Hospital for Women and Children, Canberra Hospital, Woden, Australia. 28. Neonatal Intensive Care Unit, Dunedin Hospital, Dunedin, New Zealand. 29. Department of Neonatology, Rambam Medical Center, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. 30. Division of Neonatology, Royal Brisbane and Women's Hospital, Brisbane, Australia. 31. Division of Neonatology, Peyton Manning Children's Hospital, Ascension St Vincent, Indianapolis, Indiana. 32. Neonatal Intensive Care Centre, Royal London Hospital-Barts Health NHS Foundation Trust, London, England. 33. Division of Neonatology, Sidra Medicine, Doha, Qatar. 34. Department of Pediatrics, WVU Medicine Children's Hospital, Morgantown, West Virginia. 35. Neonatal Intensive Care Unit, Princess Anne Hospital, Southampton, England. 36. Department of Neonatology, EGA Institute for Women's Health, Faculty of Population Health Sciences, University College London, London, England. 37. Division of Neonatal-Perinatal Medicine, Larner College of Medicine, University of Vermont, Burlington. 38. Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Abstract
Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.
Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.
Authors: Wolfgang Göpel; Angela Kribs; Andreas Ziegler; Reinhard Laux; Thomas Hoehn; Christian Wieg; Jens Siegel; Stefan Avenarius; Axel von der Wense; Matthias Vochem; Peter Groneck; Ursula Weller; Jens Möller; Christoph Härtel; Sebastian Haller; Bernhard Roth; Egbert Herting Journal: Lancet Date: 2011-09-29 Impact factor: 79.321
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