Clinical trial NCT05791331: REspiratory MEchanics for Delivering Individualised Exogenous Surfactant
Official title: A Randomized Controlled Trial of Oscillatory Mechanics Versus Oxygenation-based Criteria for Surfactant Therapy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Respiratory Distress Syndrome in Premature Infant
Keywords: Surfactant
Respiratory mechanics
Respiratory Oscillometry
Forced Oscillation technique
Neonatal RDS
CPAP
CPAP failure
Premature infant
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: Politecnico di Milano
First posted: 2023-03-30
Enrollment: 458
Sex: ALL
Minimum age (years): 27
Maximum age (years): 33
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: TREATMENT

Brief summary: 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:

1. to determine if a lung mechanics-based approach for administering surfactant will change treatment timing; and
2. 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).


Eligibility criteria: Inclusion Criteria:

1. Gestational age (GA) ≥ 27+0 and \< 33+0 weeks
2. 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.
3. Inborn
4. Written parental consent obtained
5. Administration of Caffeine bolus 20 mg/kg IV or PO as per standard care

Exclusion Criteria:

1. Major congenital anomalies
2. 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).
3. Surfactant therapy prior to the study entry
4. 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
5. Respiratory failure secondary to conditions other that RDS as identified by lung imaging (air leaks, lung malformations...)
6. Any clinical condition which may place the infants at undue risk as deemed by clinicians
7. Participation to trials with competitive outcomes or likely to have an impact on the primary outcome of the study
8. Outborn patients

Primary outcomes:
measure: Days of respiratory support
timeFrame: 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 outcomes:
measure: First surfactant administration
timeFrame: 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"
measure: Days of non-invasive respiratory support
timeFrame: 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"
measure: Days of invasive respiratory support
timeFrame: 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"
measure: Patients intubated and mechanically ventilated
timeFrame: 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"
measure: Patients receiving multiple surfactant doses
timeFrame: 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"
measure: Days on supplemental oxygen
timeFrame: 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"
measure: Total cumulative oxygen exposure
timeFrame: 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"
measure: Infants receiving more than 28 days of respiratory support
timeFrame: 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"
measure: Infants developing BPD
timeFrame: 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"
measure: Infants developing air-leaks
timeFrame: 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"
measure: Infants developing prematurity-associated complications
timeFrame: 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"
measure: Infants discharged home with oxygen or respiratory support
timeFrame: 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"
measure: Days to achieve full-enteral feeding
timeFrame: 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"
measure: Days of hospitalization
timeFrame: 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"
measure: Infants receiving postnatal steroids
timeFrame: 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"
Other outcomes:
Locations:
Study officials:
References: