Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial

• Published in: JAMA : the journal of the American Medical Association Vol. 330; no. 11; pp. 1054 - 1063
• Main Authors: Dargaville, Peter A, Kamlin, C. Omar F, Orsini, Francesca, Wang, Xiaofang, De Paoli, Antonio G, Kanmaz Kutman, H. Gozde, Cetinkaya, Merih, Kornhauser-Cerar, Lilijana, Derrick, Matthew, Özkan, Hilal, Hulzebos, Christian V, Schmölzer, Georg M, Aiyappan, Ajit, Lemyre, Brigitte, Kuo, Sheree, Rajadurai, Victor S, O’Shea, Joyce, Biniwale, Manoj, Ramanathan, Rangasamy, Kushnir, Alla, Bader, David, Thomas, Mark R, Chakraborty, Mallinath, Buksh, Mariam J, Bhatia, Risha, Sullivan, Carol L, Shinwell, Eric S, Dyson, Amanda, Barker, David P, Kugelman, Amir, Donovan, Tim J, Goss, Kevin C. W, Tauscher, Markus K, Murthy, Vadivelam, Ali, Sanoj K. M, Clark, Howard W, Soll, Roger F, Johnson, Samantha, Cheong, Jeanie L. Y, Carlin, John B, Davis, Peter G
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 19.09.2023
• Subjects: Age; Breathing; Catheterization; Catheters; Child, Preschool; Clinical trials; Continuous Positive Airway Pressure; Death; Dyspnea; Female; Follow-Up Studies; Gestational age; Health services; Hospitals; Humans; Illnesses; Infant; Infant, Newborn; Infant, Premature; Infants; Intensive care units; Lipoproteins; Long-term effects; Male; Mechanical ventilation; Medical instruments; Minimally Invasive Surgical Procedures; Mist; Mortality; Neonates; Newborn babies; Online First; Original Investigation; Premature babies; Pulmonary Surfactants - administration & dosage; Pulmonary Surfactants - therapeutic use; Respiration; Respiratory diseases; Respiratory distress syndrome; Respiratory Distress Syndrome - complications; Respiratory Distress Syndrome - drug therapy; Respiratory Distress Syndrome - therapy; Respiratory Distress Syndrome, Newborn - complications; Respiratory Distress Syndrome, Newborn - drug therapy; Respiratory Distress Syndrome, Newborn - therapy; Respiratory Sounds; Risk management; Surface-Active Agents - administration & dosage; Surface-Active Agents - therapeutic use; Surfactants; Wheezing
• ISSN: 0098-7484; 1538-3598; 1538-3598
• DOI: 10.1001/jama.2023.15694

IMPORTANCE: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. OBJECTIVE: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years’ corrected age. DESIGN, SETTING, AND PARTICIPANTS: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years’ corrected age was completed on December 9, 2022. INTERVENTIONS: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. MAIN OUTCOMES AND MEASURES: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years’ corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. RESULTS: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, −7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). CONCLUSIONS AND RELEVANCE: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12611000916943