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

Abstract

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.

• 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, Kevin C W Goss, Markus K Tauscher, Vadivelam Murthy, Sanoj K M Ali, Howard W Clark, Roger F Soll, Samantha Johnson, Jeanie L Y Cheong, John B Carlin, Peter G Davis, OPTIMIST-A Trial Investigators
• Journal: JAMA (JAMA) Vol. 330 Issue 11 Pg. 1054-1063 (09 19 2023) ISSN: 1538-3598 [Electronic] United States
• PMID: 37695601 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Lipoproteins
• Pulmonary Surfactants
• Surface-Active Agents
• poractant alfa

Topics

• Female
• Humans
• Infant
• Infant, Newborn
• Dyspnea
• Follow-Up Studies
• Infant, Premature
• Lipoproteins
• Pulmonary Surfactants (administration & dosage, therapeutic use)
• Respiratory Distress Syndrome (complications, drug therapy, therapy)
• Respiratory Distress Syndrome, Newborn (complications, drug therapy, therapy)
• Respiratory Sounds
• Surface-Active Agents (administration & dosage, therapeutic use)
• Catheterization
• Minimally Invasive Surgical Procedures
• Continuous Positive Airway Pressure
• Male
• Child, Preschool