Cerebral Oxygenation, Cerebral Oxygen Saturation, Infant Respiratory Distress Syndrome, Neonates and Preterm Infants, Surfactant, Surfactant Deficiency Syndrome Neonatal
Conditions
Keywords
surfactant, surfactant administration, LISA, less-invasive surfactant administration, preterm neonates, cerebral oxygenation, near-infrared spectroscopy
Brief summary
Respiratory distress syndrome (RDS) is common in very preterm infants due to surfactant deficiency. Surfactant replacement therapy is lifesaving, and current guidelines recommend the less invasive surfactant administration (LISA) technique. However, the optimal duration of surfactant instillation during LISA has never been systematically evaluated. Rapid instillation may provoke transient hypoxia and bradycardia, while slower administration might improve physiological stability and cerebral oxygenation. This randomised controlled trial investigates whether the duration of surfactant administration (1 minute versus 5 minutes) affects cerebral and systemic oxygen stability in extremely preterm neonates (\< 28 weeks).
Detailed description
The SurfStab I Trial is a single-centre, randomised, controlled, phase IV trial conducted at the Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Austria. Infants born before 28 weeks of gestation and requiring surfactant therapy via the LISA technique will be randomised (1:1) to receive poractant alfa administered over either 1 minute or 5 minutes. The intervention duration represents two clinically accepted timeframes within current guideline recommendations. Cerebral oxygenation will be monitored continuously using near-infrared spectroscopy (NIRS) from 5 minutes before to 3 hours after the procedure. The primary outcome is the maximal change in cerebral regional tissue oxygen saturation (crSO₂) from baseline (=5 minutes before starting the LISA procedure \[insertion of the LISA catheter\]) till 15 minutes after the LISA procedure (=removal of the LISA catheter). Secondary outcomes include changes in peripheral oxygen saturation (SpO₂), heart rate (HR), mean arterial blood pressure (MABP), frequency and duration of hypoxic or bradycardic episodes, and the need for repeated surfactant administration or invasive ventilation. The total sample size is 76 infants (38 per arm). The study will provide evidence on whether slower surfactant administration improves physiological stability and cerebral oxygenation.
Interventions
DRUGPoractant alfa (Curosurf®) - 1-minute administration
Poractant alfa (Curosurf®, Chiesi Pharmaceuticals) administered intratracheally via the Less Invasive Surfactant Administration (LISA) technique over 1 minute. The surfactant is instilled manually through a thin catheter under direct laryngoscopy while the infant remains on continuous positive airway pressure (CPAP) and spontaneous breathing. Pre-specified criteria for aborting the LISA procedure are prolonged bradycardia (HR \< 80 bpm) and/or arterial hypoxia (SpO2 \< 80%) over 60 seconds during surfactant administration starting after the instillation of the LISA catheter. Data of included participants with discontinuation will be collected and analysed.
DRUGPoractant alfa (Curosurf®) - 5-minute administration
Poractant alfa (Curosurf®, Chiesi Pharmaceuticals) administered intratracheally via the Less Invasive Surfactant Administration (LISA) technique over 5 minute. The surfactant is instilled manually through a thin catheter under direct laryngoscopy while the infant remains on continuous positive airway pressure (CPAP) and spontaneous breathing. Pre-specified criteria for aborting the LISA procedure are prolonged bradycardia (HR \< 80 bpm) and/or arterial hypoxia (SpO2 \< 80%) over 60 seconds during surfactant administration starting after the instillation of the LISA catheter. Data of included participants with discontinuation will be collected and analysed.
Sponsors
Medical University of Graz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Months to 72 Years
Healthy volunteers
No
Inclusion criteria
* Preterm neonate \<28+0 weeks (gestational age up to 27 weeks and 6 days) * Indication of surfactant administration via the LISA method * Postnatal age \< 72 hours
Exclusion criteria
* Invasive ventilation, indication of INSURE procedure * Severe pulmonary or cardiac malformation affecting oxygenation or congenital cerebral malformation * Preexisiting diagnose of any IVH \> grade 2 or PVH.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in cerebral oxygenation (crSO₂) during and after LISA | From baseline (= 5min before insertion of the LISA catheter) till 15 minutes after removal of the thin catheter | The primary outcome measure will be the maximum change of crSO2 from baseline till the end of the primary window (=duration of LISA administration + 15 minutes after removal of the thin catheter). Mean values of crSO2 during the 5min before intervention started is defined as the baseline. crSO2 parameters with beginning five minute before surfactant administration till 15 minutes after extubating will be assessed every minute. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in arterial oxygen saturation (SpO₂) during and after LISA | From baseline (= 5min before insertion of the LISA catheter) till 15 minutes after removal of the thin catheter | The secondary outcome measure will be the maximum change of SpO2 from baseline till the end of the primary window (=duration of LISA administration + 15 minutes after removal of the thin catheter). Mean values of SpO2 during the 5min before intervention started is defined as the baseline. SpO2 parameters with beginning five minute before surfactant administration till 15 minutes after extubating will be assessed every minute. |
| Change in heart rate (HR) during and after LISA | From baseline (= 5min before insertion of the LISA catheter) till 15 minutes after removal of the thin catheter | The secondary outcome measure will be the maximum change of HR from baseline till the end of the primary window (=duration of LISA administration + 15 minutes after removal of the thin catheter). Mean values of HR during the 5min before intervention started is defined as the baseline. HR parameters with beginning five minute before surfactant administration till 15 minutes after extubating will be assessed every minute. |
| Change in crSO2 up to three hours after LISA | Beginning of the surfactant administration (insertion of the thin catheter) till three hours after LISA procedure | The secondary outcome measures will be crSO2 up to three hours after surfactant administration defined as maximum changes/drop from starting with the beginning of the surfactant administration after insertion of the thin catheter till three hours after LISA procedure. Vital parameters will be assessed every five minutes till three hours after LISA procedure. |
| Change in SpO2 up to three hours after LISA | Beginning of the surfactant administration (insertion of the thin catheter) till three hours after LISA procedure | The secondary outcome measures will be SpO2 up to three hours after surfactant administration defined as maximum changes/drop from starting with the beginning of the surfactant administration after insertion of the thin catheter till three hours after LISA procedure. Vital parameters will be assessed every five minutes till three hours after LISA procedure. |
| Change in HR up to three hours after LISA | Beginning of the surfactant administration (insertion of the thin catheter) till three hours after LISA procedure | The secondary outcome measures will be HR up to three hours after surfactant administration defined as maximum changes/drop from starting with the beginning of the surfactant administration after insertion of the thin catheter till three hours after LISA procedure. Vital parameters will be assessed every five minutes till three hours after LISA procedure. |
| Change in mean arterial blood pressure (MABP) up to three hours after LISA | Beginning of the surfactant administration (insertion of the thin catheter) till three hours after LISA procedure | The secondary outcome measures will be MABP up to three hours after surfactant administration defined as maximum changes/drop from starting with the beginning of the surfactant administration after insertion of the thin catheter till three hours after LISA procedure. Vital parameters will be assessed every five minutes till three hours after LISA procedure. |
| Amount of bradycardia | Beginning of the surfactant administration (insertion of the thin catheter) till three hours after LISA procedure | The secondary outcome measure will be the amount of bradycardia (in minutes) up to three hours after surfactant administration |
| Amount of cerebral hypoxia | Beginning of the surfactant administration (insertion of the thin catheter) till three hours after LISA procedure | The secondary outcome measure will be the amount of cerebral hypoxia (in minutes) up to three hours after surfactant administration |
| Amount of systemic hypoxia | Beginning of the surfactant administration (insertion of the thin catheter) till three hours after LISA procedure | The secondary outcome measure will be the amount of systemic hypoxia (in minutes) up to three hours after surfactant administration |
| Amount of supplemental oxygen | Beginning of the surfactant administration (insertion of the thin catheter) till three hours after LISA procedure | The secondary outcome measure will be the amount of supplemental oxygen up to three hours after surfactant administration |
| Need for repeat surfactant administraiton | Within 48 hours after first LISA procedure | Proportion of infants requiring a second surfactant dose as per clinical indication. |
| Need for invasive ventilation | Within 48 hours after first LISA procedure | Proportion of infants requiring intubation and mechanical ventilation due to respiratory failure. |
| Bronchopulmonary dysplasia (BPD) | At 36 weeks corrected gestational age | Incidence of BPD, defined as oxygen and/or respiratory support requirement at 36 weeks postmenstrual age. |
| Intraventricular haemorrhage (IVH) | At 40 weeks of corrected age | Incidence of any IVH assessed by cranial ultrasound |
| Periventricular leukomalacia (PVL) | At 40 weeks of corrected age | Presence of cystic PVL or increased periventricular echogenicity consistent with white matter injury. |
| Retinopathy of prematurity | At 40 weeks of corrected age | Presence of ROP |
| Necrotizing enterocolitis (NEC) | At 40 weeks of corrected age | Presence of NEC |
| Mortality | At 40 weeks of corrected age | Occurence of mortality during hospital stay |
Countries
Austria
Contacts
CONTACTChristina H. Wolfsberger, Priv.Doz. DDr.
CONTACTGerhard Pichler, Univ.Prof. PD. Dr.
Outcome results
None listed