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Randomized Controlled Trial
. 2023 Sep 19;330(11):1054-1063.
doi: 10.1001/jama.2023.15694.

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

Peter A Dargaville  1   2 , C Omar F Kamlin  3   4 , Francesca Orsini  5 , Xiaofang Wang  5 , Antonio G De Paoli  2 , H Gozde Kanmaz Kutman  6 , Merih Cetinkaya  7 , Lilijana Kornhauser-Cerar  8 , Matthew Derrick  9 , Hilal Özkan  10 , Christian V Hulzebos  11 , Georg M Schmölzer  12 , Ajit Aiyappan  13 , Brigitte Lemyre  14 , Sheree Kuo  15 , Victor S Rajadurai  16 , Joyce O'Shea  17 , Manoj Biniwale  18 , Rangasamy Ramanathan  18 , Alla Kushnir  19 , David Bader  20 , Mark R Thomas  21 , Mallinath Chakraborty  22 , Mariam J Buksh  23 , Risha Bhatia  24 , Carol L Sullivan  25 , Eric S Shinwell  26 , Amanda Dyson  27 , David P Barker  28 , Amir Kugelman  29 , Tim J Donovan  30 , Kevin C W Goss  31 , Markus K Tauscher  32 , Vadivelam Murthy  33 , Sanoj K M Ali  34 , Howard W Clark  35 , Roger F Soll  36 , Samantha Johnson  37 , Jeanie L Y Cheong  3   4   38 , John B Carlin  5   39 , Peter G Davis  3   4 ; OPTIMIST-A Trial Investigators
Collaborators, Affiliations
Randomized Controlled Trial

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

Peter A Dargaville et al. JAMA. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Dargaville reported receiving personal fees from AbbVie (advisory board consultancy 2014) and Chiesi Farmaceutici (advisory board consultancies 2016, 2021) and provision of surfactant at reduced cost and support for conference travel from Chiesi Farmaceutici during the conduct of the study; in addition, Dr Dargaville has a patent for a catheter design (USD752215S) issued. Dr Hulzebos reported receiving grants from Chiesi Farmaceutici during the conduct of the study. Dr Kushnir reported receiving grants from the University of Sydney outside the submitted work. Dr Goss reported serving as chief investigator for OPTI-SURF, an observational study on UK neonatal surfactant use in respiratory distress syndrome funded by Chiesi UK outside the submitted work. Dr Clark reported receiving personal fees from Chiesi Farmaceutici outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Screening, Enrollment, Randomization, and Follow-Up
CPAP indicates continuous positive airway pressure; Fio2, fraction of inspired oxygen; and MIST, minimally invasive surfactant therapy. aAn additional 2 infants were enrolled but randomization failed in 1 case and in another was performed when the infant was ineligible (Fio2 = 0.24). Treatment allocation was not revealed in either case.
See this image and copyright information in PMC

Comment in

References

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