A Trial Comparing Noninvasive Ventilation Strategies in Preterm Infants Following Extubation
Condition: Intubated Infants Were Intend to Extubation Using Noninvasive Ventilation Strategies
MeSH terms: Respiratory Distress Syndrome
Study type: Interventional

Summary: 
      Respiratory distress syndrome (RDS) is the main cause of respiratory failure in preterm
      neonates, its incidence varying from 80% to 25% depending on gestational age.When optimal
      prenatal care is provided, the best approach to treat RDS, according to several recent
      trials,consists in providing continuous positive airway pressure (CPAP) from the first
      minutes of life using short binasal prongs or masks, followed by early selective surfactant
      administration for babies with worsening oxygenation and/or increasing work of breathing. Any
      effort should be done to minimize the time under invasive mechanical ventilation
      (IMV).Nonetheless, clinical trials have shown that a relevant proportion of preterm neonates
      fails this approach and eventually need IMV.The duration of IMV is a well known risk factor
      for the development of broncho-pulmonary dysplasia (BPD) - a condition associated with
      significant morbidity and mortality.

      To minimize the duration of IMV, various non invasive respiratory support modalities are
      available in neonatal intensive care units (NICU). CPAP is presently the most common
      technique used in this regard. However, a systematic review has shown that non-invasive
      positive pressure ventilation (NIPPV) reduces the need for IMV (within one week from
      extubation) more effectively than NCPAP, although it is not clear if NIPPV may reduce need
      for intubation longterm and it seems to have no effect on BPD and mortality. NIPPV main
      drawback is the lack of synchronization, which is difficult to be accurately achieved and is
      usually unavailable. A more recent alternative technique is non-invasive high frequency
      oscillatory ventilation (NHFOV) which consists on the application of a bias flow generating a
      continuous distending positive pressure with oscillations superimposed on spontaneous tidal
      breathing with no need for synchronization. The physiological, biological and clinical
      details about NHFOV have been described elsewhere.

      To date, there is only one small observational uncontrolled study about the use of NHFOV
      after extubation in preterm infants. Other relatively small case series or retrospective
      cohort studies suggested safety, feasibility and possible usefulness of NHFOV and have been
      reviewed elsewhere.The only randomized trial published so far compared NHFOV to biphasic
      CPAP,in babies failing CPAP and it has been criticized for methodological flaws and for not
      taking into account respiratory physiology.An European survey showed that, despite the
      absence of large randomized clinical trials, NHFOV is quite widely used, at least in some
      Countries and no major side effects are reported, although large data about NHFOV safety are
      lacking. This may be due to the relative NHFOV easiness of use but evidence-based and
      physiology-driven data are warranted about this technique.
    

Detailed description: 
      NHFOV should theoretically provide the advantages of invasive high frequency oscillatory
      ventilation (no need for synchronization, high efficiency in CO2 removal, less
      volume/barotrauma) and nasal CPAP (non-invasive interface, oxygenation improvement by the
      increase in functional residual capacity through alveolar recruitment). NHFOV should allow to
      increase mean airway pressure (Paw) avoiding gas trapping and hypercarbia, thanks to the
      superimposed high frequency oscillations. Therefore, NHFOV is more likely to be beneficial
      for those neonates requiring high distending pressure to open up their lungs, such as babies
      at high risk of extubation failure due to severity of their lung disease. This may also be
      the case of extremely preterm, BPD-developing neonates who have increased airway resistances,
      while they are subjected to a deranged alveolarization and lung growth. Neonates presenting
      with respiratory acidosis may also benefit from NHFOV. Several animal and bench studies
      investigated the physiology and peculiarities of NHFOV and these data should be used to
      conduct a physiology-guided trial in order to avoid errors done in the early trials about
      invasive high frequency ventilation.

      This study will be the first large trial aiming to compare CPAP vs NIPPV vs NHFOV in preterm
      neonates after surfactant replacement and during their entire NICU stay, to reduce the total
      need of invasive ventilation. Since there is a lack of formal data regarding NHFOV safety,
      some safety outcomes will also be considered.Specific subgroup analysis will be conducted for
      pre-specified groups of patients who may most likely benefit from NHFOV, according to the
      above-described physiological characteristics.
    

Intervention name(s): NHFOV; NCPAP; NIPPV
Intervention type(s): Device; Device; Device
Intervention description(s): Nasal high frequency oscillation ventilation (NHFOV) is used as the noninvasive supporting mode after extubation.; Nasal continuous positive airway pressure(NCPAP) is used as the noninvasive supporting mode after extubation.; Nasal intermittent positive pressure ventilation(NIPPV) is used as the noninvasive supporting mode after extubation.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: When the neonate had fulfilled the extubation criteria, extubation will took place with a gentle intratracheal suction. Upper airways will then be suctioned and intervention will be started immediately as follows:
Ventilators
CPAP: CPAP will be provided by either variable flow or continuous flow devices, as there is no evidence that one type of CPAP generator would be better than any other.
NIPPV: NIPPV will be provided by any type of neonatal ventilator. Synchronization will not be applied, as many currently marketed neonatal ventilators usually do not provide it for NIPPV.
NHFOV: NHFOV will only be provided with piston/membrane oscillators able to provide a real oscillatory pressure with active expiratory phase (that is, Acutronic FABIAN-III, SLE 5000, Loweinstein Med LEONI+, Sensormedics 3100A). Other machines providing high frequency ventilations will not be used.
Importantly, the randomization should be done within one hour from the extubation to avoid bias.
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: nasal high frequency oscillation ventilation(NHFOV); nasal continuous positive airway pressure(NCPAP); nasal intermittent positive pressure ventilation（NIPPV）; neonatal respiratory distress syndrome(NRDS); preterm infants