Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome
Authors: Peter A. Dargaville, C. Omar F. Kamlin, Francesca Orsini, Xiaofang Wang, Antonio G. De Paoli, H. Gozde Kanmaz Kutman, Merih Cetinkaya, Lilijana Kornhauser-Cerar, Matthew Derrick, Hilal Özkan, Christian V. Hulzebos, Georg M. Schmölzer, Ajit Aiyappan, Brigitte Lemyre, Sheree Kuo, Victor S. Rajadurai, Joyce O’Shea, Manoj Biniwale, Rangasamy Ramanathan, Alla Kushnir, David Bader, Mark R. Thomas, Mallinath Chakraborty, Mariam J. Buksh, Risha Bhatia, Carol L. Sullivan, Eric S. Shinwell, Amanda Dyson, David P. Barker, Amir Kugelman, Tim J. Donovan, Markus K. Tauscher, Vadivelam Murthy, Sanoj K. M. Ali, Pete Yossuck, Howard W. Clark, Roger F. Soll, John B. Carlin, Peter G. Davis, Brian A Darlow, Michael Dunn, Amy Salter, Karen Butterley, Nicky Stephens, Lizzy Reid, Ross Dunn, Luke Stephens, Tammy Matzolic, Brenda Argus, Emily Twitchell, Joanna Barrotta, Elizabeth Noble, Kenneth Tan, Emma Yeomans, Melissa Lai, Pieter Koorts, Margaret Broom, Brenda Law, Po-Yin Cheung, Sylvia Van Os, Caroline Fray, Nicole Huneault-Purney, Melissa Faulkner, Chantal Horth, Rebecca Grimwood, A Riskin, Tatiana Kalinina, C Tsafrir, S Afuta, Fanny Timstut, Sabine Huth, Frances McCaffrey, Helmut Hummler, Samir Gupta, Mary Dinan, Miriam Casiraghi, Yip Wai Yan, Krishna R Gopagondanahalli, Suresh Chandran, Rowena Dela Puerta, Miha Lučovnik, Vlasta L Kurtovič, Annelies J Olthuis, Dyvonne H Baptist, Helene A Bouma, Mehmet Büyüktiryaki, Suzan Sahin, Burcu Cebeci, Sule Ozdemir, Aylin Vantansever, Lorna McKay, Therese McSorley, Philippa Crowley, Jenny Pond, Christie Mellish, Rachel M Hayward, Ian P Morris, Sian Elliot, Deena-Shefali Patel, Izabela Andrzejewska, Amanda Cook, Sue Wolf, Micah Tong, Rosanna Ericksen, Amanda Logan, Patricia Niblack, Zenaida R Tauscher, Pamela Whitlow, Susan L Collins
Journal: JAMA (2021)

<h3>Importance</h3> The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. <h3>Objective</h3> To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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. <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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];<i>P</i> = .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];<i>P</i> = .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];<i>P</i> = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> anzctr.org.au Identifier:ACTRN12611000916943