Prophylactic Surfactant by Thin Endotracheal Catheter for Preterm Infants At Birth: the ProTeCt Trial

University College Dublin164 enrolled

Overview

The goal of this clinical trial is to learn whether giving surfactant through a thin endotracheal catheter to extremely premature babies shortly after birth reduces the number of them who are ventilated in the first 3 days of life. The main question it aims to answer is: Do fewer babies who receive prophylactic thin catheter surfactant under video laryngoscopy shortly after birth go on to be ventilated within 72 hours of birth? Extremely premature babies who are receiving breathing support through a face mask will either: * Receive surfactant through a thin catheter that is inserted into their windpipe (trachea) under video laryngoscopy at or after 5 minutes of life, have the catheter removed immediately, and return to face mask breathing support; or * Continue on face mask breathing support. All babies will be closely watched to see whether they are ventilated for breathing support in the first 72 hours of life.

Preterm infants - particularly those born before 28 weeks of gestation - are at risk of developing respiratory distress syndrome (RDS), a condition characterised by structural and functional lung immaturity that leads to progressive respiratory failure. Infants at high risk of or who show early signs of RDS are treated with continuous positive airway pressure (CPAP) in an attempt to prevent respiratory failure. Infants whose RDS worsens despite CPAP are given surfactant. To give surfactant, clinicians use a laryngoscope to view the airway and insert a relatively wide-bore endotracheal tube (ETT) directly into the trachea. When an ETT is used to deliver surfactant, the ETT usually remains in place for a period of mechanical ventilation (MV). Clinicians aim to minimise the duration of ventilation, as even short periods of MV may be harmful to the preterm lung. An alternative approach, sometimes called "less-invasive surfactant application" (LISA), is to give surfactant through a thin endotracheal catheter. These thin catheters (TC) cannot be used for mechanical ventilation and so they are immediately removed after the surfactant has been given. A Cochrane systematic review found that, compared to giving surfactant through an ETT in the NICU, TC surfactant is associated with reduced risk of death or bronchopulmonary dysplasia (BPD), less intubation in the first 72 hours and reduced incidence of major complications and in-hospital mortality. However, the studies included in the systematic review are heterogenous, few of them enrolled infants born before 28 weeks of gestation and none of them evaluated the effects of giving TC surfactant shortly after birth, before starting CPAP in the NICU. In all of these studies, the clinician inserting the TC viewed the airway directly through the mouth (i.e. performed direct laryngoscopy). Inserting an ETT in a newborn infant using direct laryngoscopy is challenging. Clinicians use clinical signs detected during positive pressure ventilation (PPV) (e.g. detection of exhaled carbon dioxide, auscultation of breath sounds, condensation in the tube in expiration) to determine whether the ETT has been placed correctly. We recently demonstrated that more first intubation attempts with an ETT in newborn infants are successful when clinicians used a video laryngoscope (VL) to view the airway indirectly compared to direct laryngoscopy. . As PPV cannot be given through a TC, the only way of determining the position of a TC is to see it enter the larynx. Using VL during TC insert attempts allows multiple observers to simultaneously and independently determine whether it is in the correct place. The earlier that surfactant is given, the more effective it appears to be. It is possible that TC surfactant given "prophylactically" - i.e. very shortly after birth, when there are minimal signs of respiratory distress - under VL guidance may substantially reduce the rate of intubation for respiratory failure. If it does, that holds out the prospect that it may reduce rates of the adverse outcomes associated with ventilation (death or BPD etc.) in preterm infants.

Outcomes

Primary Outcomes

Number of participants intubated in the first 72 hours of life

Endotracheal intubation 1. in the Delivery Room for apnoea or bradycardia despite mask PPV; or 2. in the Neonatal Intensive Care Unit, for 2 or more of * worsening clinical signs respiratory distress * oxygen requirement \> 30% for \>30 mins to keep oxygen saturation (SpO2) \>90% * pH \< 7.2 on 2 blood gases 30 minutes apart * PCO2 \>9kPa on 2 blood gases 30 minutes apart * recurrent mask PPV for apnoea Participants reach the primary outcome if they are intubated with an endotracheal tube (ETT) for mechanical ventilation, with an ETT for surfactant and mechanical ventilation, with an ETT for surfactant alone, or with a thin catheter for surfactant alone

Time frame: First 72 hours of life

Secondary Outcomes

Number of participants in whom the thin catheter is seen on video laryngoscopy to be successfully inserted at first attempt (intervention group only)

Success at first thin catheter insertion attempt (intervention group only)

Time frame: 30 minutes

Number of participants with bradycardia [heart rate (HR) < 100bpm] in the Delivery Room (DR)

Bradycardia (HR \< 100bpm) in the DR

Time frame: 30 minutes

Number of participants who receive mask Positive Pressure Ventilation (PPV) in the DR

Mask PPV in the DR

Time frame: 30 minutes

Number of participants who undergo endotracheal intubation in the DR

Endotracheal intubation in the DR

Time frame: 30 minutes

Number of participants who receive chest compressions in the DR

Chest compressions in the DR

Time frame: 30 minutes

Number of participants who receive adrenaline in the DR

Adrenaline administration in the DR

Time frame: 30 minutes

Number of participants who receive volume expansion in the DR

Volume expansion in the DR

Time frame: 30 minutes

Number of participants who are itubated at any time during hospitalisation

Intubation at any time during hospitalisation