Synchronized Intermittent Mandatory Ventilation (SIMV) Versus Nasal Intermittent Positive Pressure Ventilation (NIPPV) In Preterm Infants With Respiratory Distress
Condition: Respiratory Distress Syndrome, Newborn
MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn
Study type: Interventional
Phase: Phase 4

Summary: 
      Title of Study: A Prospective, Randomized, Multicenter Trial Comparing Synchronized
      Intermittent Mandatory Ventilation (SIMV) vs. Early Extubation to Nasal Intermittent Positive
      Pressure Ventilation (NIPPV) after Surfactant Treatment in Preterm Infants with Respiratory
      Distress Treatment Period (Planned): 7 days Objectives: To compare the impact of early
      extubation [within 120 minutes of birth to Nasal Intermittent Positive Pressure Ventilation
      (NIPPV group) vs. Synchronized Intermittent Mandatory Ventilation (SIMV group) on the
      incidence of mechanical ventilation via endotracheal tube at 7 days of age in 26 to 29 + 6
      weeks gestation premature infants with respiratory distress treated with intratracheal
      Curosurf (poractant alpha) within 60 minutes of birth.

      Secondary objectives include evaluation of overall clinical outcomes at 7 days, 28 days, and
      36 weeks postmenstrual age (PMA) and/or at discharge, complications, safety, and adverse
      events.

      Number of Subjects: 110
    

Detailed description: 
      Respiratory management: SIMV group:

      Infants randomized to SIMV will be maintained on SIMV per standard unit protocol. Infant can
      be progressively weaned and extubated to NCPAP if infant meets the minimum criteria for
      extubation. Caffeine will be administered around the time of extubation.

      NIPPV group:

      Extubated to NIPPV within 120 minutes of birth if the fraction of inspired oxygen (FiO2) is
      less than 0.60 after the first dose of surfactant. Caffeine will be administered around the
      time of extubation. Infant can be reintubated if clinical parameters necessitate mechanical
      ventilation. NIPPV may be discontinued when patients are weaned to a positive end expiratory
      pressure of 5 cmsH20 with back up rate <10 bpm and FiO2 <0.30 for 24 hours to nasal
      continuous positive airway pressure (NCPAP).

      Surfactant administration:

      Prior to randomization and enrollment, infants will receive an initial dose of poractant alfa
      200mg/kg. Subsequent doses of 100mg/kg can be given 12 hours after the initial dose based
      upon clinical criteria. Up to 2 additional doses can be given within 48 hours of age in
      infants who remain intubated.

      Criteria for Evaluation Primary Endpoint: The need for mechanical ventilation via the
      endotracheal tube at 7 days of age.

      Secondary Endpoints: Additional doses of surfactant, duration (days) of mechanical
      ventilation, duration (days) of supplemental oxygen, days on NIPPV, days on CPAP, use of
      postnatal steroids for bronchopulmonary dysplasia (BPD), death before discharge,
      pneumothorax, pneumomediastinum, pneumopericardium, pulmonary hemorrhage, patent ductus
      arteriosis (PDA), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL),
      necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), growth (weight on day 28
      and 36 weeks PMA, and/or discharge), length of hospital stay.

      Adverse events (AEs) and serious adverse events (SAEs) will be monitored, collected,
      analyzed, and reported.

      Safety will be monitored throughout the study and will be based on prospectively defined
      complications (safety outcomes) and will allow for reporting of as yet unidentified potential
      complications.

      All AEs and SAEs will be reported, with SAEs reported on an expedited basis per regulatory
      requirements and timeframes to the responsible investigational review boards (IRBs), and the
      Data Safety Monitoring Board (DSMB). Interim analysis will be performed by an independent
      statistician after 50 patients are enrolled and data will be submitted to the DSMB members.
      They will monitor for any adverse events, specifically, mortality and make a recommendation
      about continuation of the study. The DSMB will not disclose any findings to avoid any biases
      except to issuing a continue or discontinue statement. If there is a statistically
      significant difference in the primary endpoint- the need for mechanical ventilation via
      endotracheal tube at 7 days of age (p < 0.02) or statistically higher incidence in mortality
      within one of the treatment groups, the trial can be closed and these midpoint results will
      be disclosed.

      Statistical Methods Sample Size: A sample size of 100 patients is needed. The need for
      mechanical ventilation via endotracheal tube at 7 days of age in this preterm population has
      been reported to range between 63% (Verder 1999) and 43% (Dani 2004). On the basis of data
      collected from our own center and from published data in VLBW infants, a sample size of 50
      infants in each group will be needed to demonstrate a 50% reduction in the need for
      mechanical ventilation via endotracheal tube at 7 days of age (power of 0.8 and an α-error of
      0.05). An additional 10 patients (10%) will be allowed for to accommodate for dropouts.

      Primary Endpoint: Analyses of the primary endpoint will be based on intention to treat (ITT)
      analysis of all randomized, eligible subjects. Statistical analyses will be performed by
      using Student's t test for continuous normally distributed variables and with the Wilcoxon
      rank sum test for non-parametric variables. Comparison of proportions and analysis of
      categorical variables will be performed using 2-tailed Fisher's exact test and logistic
      regression analysis. A p value of < 0.05 will be considered statistically significant.

      Secondary Endpoints: The secondary efficacy analyses will be performed using the ITT
      population. The following secondary variables that will be analyzed include need for
      additional doses of surfactant, duration of mechanical ventilation and supplemental oxygen,
      days on nasal CPAP, postnatal steroid use for BPD, growth (weight on day 28 and 36 weeks PMA,
      and/or discharge) and length of hospital stay. A p-value of less than 0.05 will be considered
      significant for testing the effect of each factor. A multiple regression analysis may be
      employed as required if confounding effects are identified within the study (e.g.,
      gestational age, race, center, antenatal or postnatal steroid use).
    

Intervention name(s): Extubation to Nasal IPPV
Intervention type(s): Other
Intervention description(s): Comparison of extubation to NIPPV versus NCPAP
Other intervention name(s): NIPPV; SIMV
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: RDS; Preterm; SIMV; NIPPV