The NONA-LISA Trial

Respiratory Distress Syndrome in Premature Infant Clinical Trial

— NONA-LISA  

Official title:

The NON-pharmacological Approach Less Invasive Surfactant Administration Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05609877
• Other study ID #: NONA-LISA
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 1, 2023
• Est. completion date: May 31, 2029

Study information

• Verified date: March 2023
• Source: Rigshospitalet, Denmark
• Contact: Lise Aunsholt, MD, PhD
• Phone: +4561991137
• Email: lise.aunsholt[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 324
• Est. completion date: May 31, 2029
• Est. primary completion date: April 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Weeks to 30 Weeks

Eligibility

Inclusion Criteria:

• Infants born at one of the trial sites with a gestational age of 24+0 to 29+6 weeks and meeting the criteria for surfactant treatment by LISA.

Exclusion Criteria:

1. prolonged premature rupture of membrane more than three weeks and suspicion of oligohydramnios or lung hypoplasia,

2. endotracheal intubation at any time before LISA,

3. suspicion of pneumothorax, pulmonary haemorrhage or pleural effusion,

4. major congenital anatomical anomalies as described by the European Surveillance of Congenital Anomalies (EUROCAT).

Related Conditions & MeSH terms

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

Intervention

Procedure:
• NONA-LISA
The staff will perform Less Invasive Surfactant Administration using the standard pre- and post-procedure care including non-pharmacological treatment. The patients will not receive pharmacological analgesic treatment routinely.

Locations

Country	Name	City	State
Denmark	Neonatalafsnittet, Børn- og Ungeafdelingen, Reberbansgade 15	Aalborg
Denmark	Department of Paediatrics (Intensive Care Neonatology) and Perinatal Research Unit	Aarhus
Denmark	Department of Neonatal and Pediatric Intensive Care, Blegdamsvej 9	København
Denmark	H.C. Andersen Børne- og Ungehospital, Kløvervænget 23C, Indgang 60	Odense

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LISA failure within 24 hours.	The primary outcome will be LISA failure in terms of the need for endotracheal intubation and mechanical ventilation for at least 30 minutes (cumulated) within 24 hours after the procedure.	24 hours after procedure.
Secondary	Incidence of additional fentanyl administration including number of injection(s), dosage, cumulated dose, and indications defined as pain/discomfort/sedation/other.		During the procedure, an average of 5-10 minutes.
Secondary	Pain or discomfort during the procedure (according to COMFORTneo score >14).		24 hours after procedure
Secondary	Bradycardia <100 BPM for a minimum duration of 4 seconds.		24 hours after procedure.
Secondary	Apnoea that require bag and mask ventilation during the procedure		24 hours after procedure.
Secondary	Desaturation with SaO2 (right extremity measure) <80% for a minimum duration of 10 seconds.		24 hours after procedure.
Secondary	Procedural time consumption from the introduction of the laryngoscope blade into the oral cavity to removal of the catheter.		24 hours after procedure.
Secondary	Number of attempts of insertion of the catheter in the trachea.		24 hours after procedure.
Secondary	Time from meeting the criteria for surfactant treatment until the procedure starts.		24 hours after procedure.
Secondary	Incidence of endotracheal intubation.		48 hours after procedure
Secondary	Incidence of pneumothorax within 48 hours after LISA.		48 hours after procedure.
Secondary	Incidence of massive pulmonary haemorrhage within 48 hours after LISA (defined as the aspiration of haemorrhagic secretions from the trachea concurrent with the need for escalated respiratory support).		48 hours after procedure.
Secondary	Incidence of in-hospital mortality before discharge.		Through study completion, an average of 6 months.
Secondary	Cumulated duration of mechanical ventilation during hospitalisation.		Before discharge (through study completion, an average of 6 months).
Secondary	Cumulated duration of positive pressure ventilation during hospitalisation.		Before discharge (through study completion, an average of 6 months).
Secondary	Cumulated duration of all types of non-invasive respiratory support during hospitalisation.		Before discharge (through study completion, an average of 6 months).
Secondary	Cumulated duration of oxygen treatment with fraction of inspired oxygen (FiO2) >0.21.		Before discharge (through study completion, an average of 6 months).
Secondary	Cumulated duration of any repisratory support during hospitalisation.		Before discharge (through study completion, an average of 6 months).
Secondary	Duration of hospitalisation.		Before discharge (through study completion, an average of 6 months).
Secondary	Incidence of necrotising enterocolitis (according to Bell's Staging Criteria).		Before discharge (through study completion, an average of 6 months).
Secondary	Incidence of treatment-demanding retinopathy of prematurity.		Before discharge (through study completion, an average of 6 months).
Secondary	Incidence of intraventricular haemorrhage grade 3-4 and periventricular leukomalacia.		Before discharge (through study completion, an average of 6 months).
Secondary	Composite outcome of death or moderate/severe BPD at 36 weeks of corrected gestational age.		36 weeks of corrected gestational age.