Intratracheal Budesonide/Surfactant Prevents BPD
Condition: Respiratory Distress Syndrome; Bronchopulmonary Dysplasia
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Bronchopulmonary Dysplasia
Study type: Interventional
Phase: Phase 4

Summary: 
      A double-blind study includes: 1) birth Wt 500-1499 gm, 2) respiratory distress shortly after
      birth and requires resuscitation 3) failure to NCPAP within 4 hrs after birth, defined as: a)
      FIO2 ≥ 0.30, pressure > 5cmH2O b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg. Exclusion
      criteria: 1) lethal cardiopulmonary status 2) severe congenital anomalies.

      Given the COVID19 pandemics, the recruitment became difficult. Under the consideration of
      scientific and practical consideration, we therefore determine to have a sample of 300, (150
      in each group), fulfill the criteria of type I error 0.05, type II error 0.10, power 90% and
      with an expectation of 30 % improvement of primary outcome (from 60 % in control group to 40
      % in the intervention group as original presumed).Appropriate amount of placebo will be used
      as it does not affect the biophysical property of curosurf (PAS abstract 2017 San Francisco).
      Primary outcome of study is death or BPD defined by NICHD criteria. Follow up study of
      neuromotor and cognitive function and pulmonary states will be done at 1-2 years of corrected
      age.
    

Detailed description: 
      A double-blind study will be conducted in 7 tertiary centers. Inclusion criteria are: 1)
      birth Wt 500-1499 gm, 2) respiratory distress shortly after birth and requires resuscitation
      3) failure to NCPAP within 4 hrs after birth, defined as: a) FIO2 ≥ 0.30, pressure > 5cmH2O
      b) severe retraction c) apnea d) PCO2 ≥ 60 mmHg. Exclusion criteria: 1) lethal
      cardiopulmonary status 2) severe congenital anomalies.

      The initial sample size was determined based on the expectation of 30% improvement of the
      primary outcome (BPD/death) in the intervention group (Curosurf + budesonide) (40%), as
      compared to control group (Curosurf +saline placebo) (60%), specifying a type I error of 0.05
      and type II error 0.20. The total number needed was 240 (120 in each group). The study was
      started in June 2019 before the pandemic of COVID19 and the study went on smoothly in 2019.
      Because of the smooth enrollment of the patients in 2019, we decided to increase the ability
      of the study for detecting the intervention effect through increasing the power from 80 % to
      90 % (type II error from 0.2 to 0.1 and type I error decreased from 0.05 to 0.02). The total
      sample size required was estimated to be 350 (170 in each group). Given the COVID19
      pandemics, the recruitment became difficult. Under the consideration of scientific and
      practical consideration, we therefore determine to have a sample of 300, (150 in each group),
      fulfill the criteria of type I error 0.05, type II error 0.10, power 90% and with an
      expectation of 30 % improvement of primary outcome (from 60 % in control group to 40 % in the
      intervention group as original presumed). The changes in sample size had been approved by
      independent monitoring committee. We expect that the study will be completed in September
      2022.

      The sample will be stratified based on birth weight (500-749 grams, 750-999 grams and
      1000-1499 grams), the presence of clinical chorioamnionitis or not, and site of study.
    

Intervention name(s): budesonide; Saline
Intervention type(s): Drug; Drug
Intervention description(s): Intra-tracheal instillation of a combination of budesonide/surfactant in preterm infants with RDS to prevent BPD; Intra-tracheal instillation of a combination of saline/surfactant in preterm infants with RDS to prevent BPD
Other intervention name(s): pulmicort; sodium chloride
Intervention MeSH terms: Budesonide
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a double blind randomized trial. The infants will be randomly assigned into 2 groups: Control (C) (curosurf + saline) and Intervention (I) (curosurf+ budesonide).
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: BPD; surfactant; budesonide; respiratory distress syndrome