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Effect of minimally invasive surfactant therapy on death or bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome (OPTIMIST-A trial).

 

Dargaville, P. A., Kamlin, C. O. F., Orsini, F., Wang, X., De Paoli, A. G., Kanmaz Kutman, H. G., Cetinkaya, M., Kornhauser-Cerar, L., Derrick, M., Özkan, H., Hulzebos, C. V., Schmölzer, G. M., Aiyappan, A., Lemyre, B., Kuo, S., Rajadurai, V. S., O’Shea, J., Biniwale, M., Ramanathan, R., Kushnir, A., … OPTIMIST-A Trial Investigators (2021). Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial. JAMA, 326(24), 2478–2487.

 

Introduction

 
 

Preterm infants with respiratory distress syndrome (RDS) supported with continuous positive airway pressure (CPAP) often require surfactant therapy.
The OPTIMIST-A trial examined the effect of selective application of a method of administrating surfactant called minimally invasive surfactant therapy (MIST) at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia.
The primary outcome of the trial was the composite of death or bronchopulmonary dysplasia (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.

 

Study design:

 

This was a multicentre, randomised, controlled trial conducted at 33 neonatal intensive care units (NICUs) across 11 countries between 2011 and 2020. The study was designed to evaluate the effect of minimally invasive surfactant therapy MIST on the incidence of death or bronchopulmonary dysplasia BPD in preterm infants with RDS. 

 
 

Participants (n=485)

  • Exclusion criteria: infants with significant congenital anomalies, already intubated, requiring resuscitation at birth, or with an identifiable alternate cause for RDS (e.g. congenital pneumonia or pulmonary hyperplasia)
 
 

Randomisation 

  • Infants were randomised 1:1 to the MIST group or the sham treatment (control) group
  • Randomisation was stratified by gestational age (25–26 weeks or 27–28 weeks)
 
 

Interventions

  • MIST group: Infants received CUROSURF (200 mg/kg), administered via a thin catheter inserted into the trachea under direct laryngoscopy 
  • Sham procedure: The control group underwent a similar handling procedure to mimic the MIST technique but without catheter insertion or surfactant administration
 
 

Outcomes

  • Primary outcome
    • Composite of death or physiological BPD at 36 weeks’ PMA 
  • Key clinical and safety outcomes:
    • Pneumothorax requiring drainage 
    • Need for intubation within 72 hours of birth 
    • Grade III/IV intraventricular haemorrhage (IVH) 
    • Death or major morbidity during the first hospitalisation
    • Death during the first hospitalisation
    • Major morbidity during the first hospitalisation in survivors


 

Adapted from Dargaville, et al 2021.

 

Results:

 
 

Primary outcomes:

 
  • The composite of death or BPD occurred in 43.6% of infants in the MIST group and 49.6% in the control group (relative risk [RR], 0.87; 95% confidence interval [CI], 0.74–1.03; p=0.10).  
  • Death prior to 36 weeks’ postmenstrual age occurred in 10.0% of MIST infants compared with 7.8% in the control group (RR, 1.27; 95% CI, 0.63–2.57; p=0.51) 
  • BPD in survivors to 36 weeks was significantly lower in the MIST group compared with the control group (37.3% vs. 45.3%; RR, 0.83; 95% CI, 0.70–0.98; p=0.03). 
 
 

Key clinical and safety outcomes:

 

There was a significant reduction in the need for intubation within 72 hours in the MIST group compared with the control group (36.5% vs. 72.1%; p<0.001). The incidence of pneumothorax requiring drainage was also significantly lower in the MIST group (4.6% vs. 10.2%; p=0.005) (Figure 2).

 

Survivors in the MIST group experienced less major morbidity during hospitalisation (41.3% vs 51.8%; p=0.05). There was no significant difference in death or major morbidity during first hospitalisation (or individual components of the composite), or Grade III/IV IVH rates between the treatment groups (Figure 2).

 

Secondary outcomes (Table 2):

 
  • The MIST group showed reductions in key outcomes compared with the control group:
    • Intubation at any time (54.8% vs. 81.1%; RR, 0.67)
    • Need for oxygen therapy at home (14.7% vs. 21.9%; RR, 0.68)
    • PDA requiring medical therapy (35.3% vs. 45.5%; RR, 0.77)
    • Surfactant therapy via endotracheal tube (32.8% vs. 68.4%).
  • MIST also reduced respiratory support durations compared with the control group:
    • MV (1 day vs. 4 days; median difference −1.96 days)
    • CPAP (17 days vs. 22 days; median difference −4.62 days)
    • Combined MV and CPAP (25 days vs. 32 days; median difference −8.13 days)
    • Total respiratory support (40 days vs. 45 days; median difference −6.42 days)
 

Adapted from Dargaville, et al 2021.

 

 

Conclusion:

 

While MIST did not significantly reduce the composite outcome of death or BPD at 36 weeks’ postmenstrual age, it was associated with a lower incidence of BPD in survivors, reduced need for intubation, and fewer days of invasive respiratory support. These findings suggest that MIST may provide clinical benefits in managing RDS in preterm infants, particularly in reducing ventilator-associated complications. 

 
 
 

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Abbreviations

 

Apgar, appearance, pulse, grimace, activity, and respiration; BPD, bronchopulmonary dysplasia; CI, confidence interval; CPAP, continuous positive airway pressure; FiO₂, fraction of inspired oxygen; IVH, intraventricular haemorrhage; IQR, interquartile range; MIST, Minimally invasive surfactant therapy; MV, mechanical ventilation; NICU, neonatal intensive care unit; PDA, patent ductus arteriosus; PMA, postmenstrual age; RDS, respiratory distress syndrome; ROP, retinopathy of prematurity; RR, relative risk; SD, standard deviation; cm H2O, centimetres of water pressure.

 
 

References

  1. Dargaville PA, et al. Clinical summary: Effect of minimally invasive surfactant therapy on death or bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome (OPTIMIST-A trial). JAMA. 2021;326(24):2478–2487.
 
 

IE-CUR-2500006 | April 2025

 

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