The NONA-LISA Trial — NONA-LISA  

Respiratory Distress Syndrome in Premature Infant Clinical Trial

Official title: The NON-pharmacological Approach Less Invasive Surfactant Administration Trial

Status Not yet recruiting

Clinical Trial Summary

The NONA-LISA trial will be an investigator-initiated, multicentre, pragmatic, parallel-group, blinded RCT conducted at four university hospitals across Denmark. A total of 324 inborn premature infants will be included within 36 months at four neonatal intensive care units (NICUs) across Denmark (approximately 2 infants per month per unit).

The aim is to compare LISA using a non-pharmacological approach alone with routine analgesic treatment combined with a non-pharmacological approach (according to local guidelines) regarding LISA failure defined as the need for positive pressure ventilation for 30 min or more (cumulated) within 24 hours after the procedure in infants born prior to 30 gestational weeks.

Clinical Trial Description

Background

Less Invasive Surfactant Administration (LISA) is a way of applying surfactant in the trachea by use of a catheter during spontaneous breathing and after applying nasal continuous positive airway pressure (nCPAP). However, use of pre-procedure analgesia with risk of apnoea may prevent LISA to achieve its full potential.

Aim

This study aims to compare the LISA procedure using a non-pharmacological approach to the LISA procedure using analgesic treatment with 0.5-1 mcg/kg fentanyl in infants born at 24 to 29 completed gestational weeks who fulfil the criteria for surfactant treatment.

Trial design

The NONA-LISA trial will be an investigator-initiated, multicentre, pragmatic, parallel-group, blinded RCT conducted at four university hospitals across Denmark. A total of 324 inborn premature infants will be included within 36 months at four neonatal intensive care units (NICUs) across Denmark (approximately 2 infants per month per unit).

Participants

Eligible infants will be born at 24+0 to 29+6 weeks of gestation meeting the criteria for surfactant treatment by LISA and not meeting any of the exclusion criteria:

• PPROM >3 weeks and suspicion of oligohydramnion or lung hypoplasia

• Requiring intubation or mechanical ventilation at any time before randomisation

• Suspicion of pneumothorax or pulmonary haemorrhage or pleural effusion

• Major congenital malformation (e.g., congenital heart disease, oesophageal atresia, esophago-tracheal fistula, diaphragmatic hernia, abdominal wall defect) or chromosomal abnormality or inherited disorders of metabolism

Interventions

The randomisation will be stratified according to trial site and gestational age (GA) less than 28 or 28+ gestational weeks. Both groups will receive treatment by experienced teams of neonatal nurses and neonatologists. Both groups will receive the non-pharmacological approach as the basic treatment (part of routine). Additional analgesics will be provided at the discretion of the clinician. Patients will receive the unit's standard pre- and post-procedure care, and both procedures will use video laryngoscopes.

Participants in the control group will receive surfactant after receiving intravenous analgesics.

Participants in the intervention group (LISA using the non-pharmacological approach) will receive surfactant after receiving a similar volume of intravenous isotonic saline solution.

Outcomes

The primary outcome will be LISA failure in terms of the need for endotracheal intubation and mechanical ventilation more than 30 minutes (cumulated) within 24 hours after the procedure. Secondary outcomes are outlined in the Outcome section.

Sample size

We have calculated our sample size based on the primary outcome with an alpha of 5%, a power of 80%, and a ratio of 1:1 between intervention and control groups.

Based on previous studies, we anticipate an incidence of "positive pressure ventilation for at least 30 minutes (cumulated) within 24 hours after procedure" in the control group around 45%. Using 30% incidence reduction as anticipated intervention effect, we will need to randomise a total of 324 infants. ;

Related Conditions & MeSH terms

• Respiratory Distress Syndrome
• Respiratory Distress Syndrome in Premature Infant
• Respiratory Distress Syndrome, Newborn

• NCT number: NCT05609877
• Study type: Interventional
• Source: Rigshospitalet, Denmark
• Contact: Lise Aunsholt, MD, PhD
• Phone: +4561991137
• Email: lise.aunsholt@regionh.dk
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2023
• Completion date: May 31, 2029