Trial Overview

Study participants

Preterm infants 25-28 weeks gestation, age <6 hrs

Entry criteria

  1. Requiring CPAP or nasal IPPV because of respiratory distress.
  2. CPAP pressure of 5-8 cm H2O and FiO2 ≥0.30.
  3. Agreement of the Treating Physician in charge of the infant's care.
  4. Signed parental consent.

Exclusion criteria

  1. Previously intubated, or in imminent need of intubation because of respiratory distress, apnoea or persistent acidosis. 
  2. Congenital anomaly or condition that might adversely affect breathing.
  3. Identifiable alternative cause for respiratory distress (e.g. congenital pneumonia or pulmonary hypoplasia).
  4. Lack of availability of an OPTIMIST treatment team.

Randomisation

With parental consent, eligible infants will be randomly allocated to receive exogenous surfactant via MIST, or to continue on CPAP.

Intervention

Infants randomised to surfactant treatment will receive a dose of surfactant (CurosurfTM, Chiesi Farmaceutici) administered via the Hobart method of MIST (see video) at a dosage of 200 mg/kg. CPAP will thereafter be reinstituted. Controls will continue on CPAP. The intervention will be masked from the clinical team.

Post-intervention management

Other than the requirement to adhere to intubation criteria, management after intervention will be at the discretion of the clinical team. Enrolled infants on CPAP will be intubated if FiO2 ≥0.45 or if there is unremitting apnoea or persistent acidosis.

A room air trial will be conducted in selected infants at 36 weeks corrected gestational age.

Primary outcome

Incidence of composite outcome of death by 36 weeks corrected gestation or physiological bronchopulmonary dysplasia (BPD)

Secondary outcomes

Incidence of death, major neonatal morbidities (CLD, intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotising enterocolitis), pneumothorax and patent ductus arteriosus; need for intubation and surfactant therapy; durations of each form of mechanical respiratory support, intensive care stay and hospitalisation; hospitalisation cost; applicability and safety of the MIST procedure; and outcome at 2 years

Sample size

606 infants (303 per group), giving 90% power to detect a 33% reduction in death or BPD from the anticipated rate of 38% in the control arm, α = 0.05.

Trial plan

The OPTIMIST-A trial has commenced at four Australian and 16 international sites. It is expected that 30+ Australian and international centres will ultimately participate. The OPTIMIST-A trial was successful in obtaining a NHMRC grant for the years 2013-2017. We expect recruitment for the trial will be completed by the end of 2017.

Outcome and significance

MIST therapy appears to have the potential to ease the burden of respiratory morbidity in preterm infants starting life on CPAP, to reduce time on respiratory support, and, as a result, to save money. The trials will give a definitive picture of the place of MIST in the care of preterm infants.

Back to top