REspiratory MEchanics for Delivering Individualised Exogenous Surfactant

Study Overview
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Brief Summary
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This study is an interventional, non-pharmacological, multicentric, randomized, controlled, superiority, non-profit study. Its primary objective is to evaluate if the administration of surfactant based on FOT assessment will allow a 5-day reduction in the duration of respiratory support as compared to standard practice in preterm infants between 27+0 and 32+6 weeks' gestation. The secondary objectives are: to determine if a lung mechanics-based approach for administering surfactant will change treatment timing; and to assess the impact of the novel approach on other neonatal general outcomes. The study will take place within the neonatal intensive care units. Non-invasive respiratory support will be delivered by nasal CPAP with a starting pressure of 5-8 cmH2O. FiO2 will be titrated in order to achieve the target SpO2 91-95%. Infants matching the clinical criteria for inclusion will be randomized in two arms following the current data protection and confidentiality regulations. Central, computer-generated randomization (allocation 1:1) with variable block sizes according to gestational age will be used. Infants will be stratified according to gestational age (27+0 -28+6 weeks; 29+0 -30+6 weeks; 31+0 -32+6 weeks) and center. Study Arms: A) Surfactant administration following oxygenation-based criteria (clinical assessment) (control) B) Surfactant administration following both lung mechanics assessment OR oxygenation-based criteria (clinical assessment) (intervention).

Official Title
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A Randomized Controlled Trial of Oscillatory Mechanics Versus Oxygenation-based Criteria for Surfactant Therapy

Conditions
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Respiratory Distress Syndrome in Premature Infant

Intervention / Treatment
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* Other: Surfactant administration following lung mechanics assessment in addition to clinical assessment
* Other: Surfactant administration following clinical assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age (GA) ≥ 27+0 and < 33+0 weeks Spontaneously breathing infants, requiring non-invasive respiratory support (nasal CPAP or bilevel nasal CPAP). Criteria for commencement of non-invasive respiratory support: FiO2 >0.30 for target SpO2 88-93% or Silverman score ≥ 5. Inborn Written parental consent obtained Administration of Caffeine bolus 20 mg/kg IV or PO as per standard care Exclusion Criteria: Major congenital anomalies Need of intubation in delivery suite according to the AAP guidelines for neonatal resuscitation or early at the admission in NICU (within one hour from birth). Surfactant therapy prior to the study entry Severe birth asphyxia, defined by APGAR score ≤ 5 at 10 minutes after birth OR continued need for resuscitation 10 minutes after birth OR pH < 7.0 or base excess (BE) < -12 mmol/l on umbilical cord or on an arterial or capillary blood sample obtained within 1 hour from birth OR moderate to severe encephalopathy Respiratory failure secondary to conditions other that RDS as identified by lung imaging (air leaks, lung malformations…) Any clinical condition which may place the infants at undue risk as deemed by clinicians Participation to trials with competitive outcomes or likely to have an impact on the primary outcome of the study Outborn patients

Ages Eligible for Study
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Minimum Age: 27 Weeks
Maximum Age: 33 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A/Control<br>Surfactant administration following clinical assessment | Other: Surfactant administration following clinical assessment<br>* Surfactant is administered following oxygenation-based criteria<br>|
| Experimental: B/Intervention<br>Surfactant administration following both lung mechanics assessment and clinical assessment | Other: Surfactant administration following lung mechanics assessment in addition to clinical assessment<br>* Surfactant is administered following oxygenation-based criteria and if the Xrs is ≤ -23.3 cmH2O*s /L<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of respiratory support | Number of days of required respiratory support | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First surfactant administration | Time of first surfactant administration (in hours) | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Days of non-invasive respiratory support | Number of days of non-invasive respiratory support | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Days of invasive respiratory support | Number of days of invasive respiratory support | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Patients intubated and mechanically ventilated | Number of patients intubated and mechanically ventilated | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Patients receiving multiple surfactant doses | Number of patients receiving multiple surfactant doses | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Days on supplemental oxygen | Number of days on supplemental oxygen | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Total cumulative oxygen exposure | Total cumulative oxygen exposure computed as the time integral of the FiO2 values | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Infants receiving more than 28 days of respiratory support | Number of infants receiving more than 28 days of respiratory support | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Infants developing BPD | Number of infants developing BPD according to the definition by NICHD 2016 | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Infants developing air-leaks | Number of infants developing air-leaks | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Infants developing prematurity-associated complications | Number of infants developing prematurity-associated complications (severe intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), sepsis, retinopathy of prematurity (ROP), patent ductus arteriosus requiring pharmacological or surgical treatment) | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Infants discharged home with oxygen or respiratory support | Number of infants discharged home with oxygen or respiratory support | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Days to achieve full-enteral feeding | Number of days to achieve full-enteral feeding (160 ml/kg/day of milk intake) | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Days of hospitalization | Number of days of hospitalization | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 
| Infants receiving postnatal steroids | Number of infants receiving postnatal steroids | From date of randomization until the date of discharge from hospital or date of death from any cause, whichever came first, assessed up to 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surfactant, Respiratory mechanics, Respiratory Oscillometry, Forced Oscillation technique, Neonatal RDS, CPAP, CPAP failure, Premature infant