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Recruiting NCT05609877

The NONA-LISA Trial

No phase Interventional Respiratory Distress Syndrome in Premature Infant

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Isotonic saline, Less Invasive Surfactant Administration (LISA), Fentanyl, Non-pharmacological standard operating procedure.
Who it may be relevant to
Registry conditions: Respiratory Distress Syndrome in Premature Infant. Basic parameters: 24 Weeks — 30 Weeks · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Denmark
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

NON-pharmacological Approach Less Invasive Surfactant Administration (NONA-LISA) Trial: Protocol for a Randomised Controlled Trial

Overview

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.

Detailed 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 at one of the trial sites meeting the criteria for first-choice surfactant treatment by LISA as described by Sweet et al.: worsening babies with RDS and FiO2 \> 0.30 on CPAP pressure ≥6 cm H2O. Infants will be excluded if they have any of the exclusion criteria: 1) suspicion of lung hypoplasia, 2) endotracheal intubation at any time before randomisation, 3) suspicion of pneumothorax, pulmonary haemorrhage or pleural effusion before LISA, 4) major congenital anatomical anomalies as described by the European Surveillance of Congenital Anomalies (EUROCAT).

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 the routine). Additional analgesics will be provided at the clinician's discretion. Patients will receive the unit's standard pre-procedure 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 of this trial is the need for invasive ventilation, meaning mechanical or manual ventilation via an endotracheal tube for at least 30 min (cumulated) within 24 h of the procedure. Non-invasive ventilation (NIV) is not included in the primary outcome.

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.

Interventions

  • Drug Isotonic saline
    Isotonic saline will be administered intravenously instead of pre-procedure analgesia.
  • Procedure Less Invasive Surfactant Administration (LISA)
    All infants will be treated with the Less Invasive Surfactant Administration (LISA) procedure
  • Drug Fentanyl
    Fentanyl 0.5-1.0 mcg/kg will be administered intravenously as pre-procedure analgesia
  • Behavioral Non-pharmacological standard operating procedure
    All infants will receive the same non-pharmacological standard operating procedure.

Primary outcome measures

  • LISA failure within 24 hours. [Time frame: 24 hours after procedure.]
Secondary outcome measures (12)
  • Incidence of additional fentanyl administration [Time frame: During the procedure, an average of 5-10 minutes.]
  • Pain or discomfort during the procedure (according to COMFORTneo score >14). [Time frame: 24 hours after procedure]
  • Bradycardia <100 BPM for a minimum duration of 4 seconds. [Time frame: 24 hours after procedure.]
  • Need for a second dose of surfactant [Time frame: 24 hours after procedure.]
  • Escalation from LISA to INSURE in the same attempt [Time frame: 24 hours after procedure.]
  • Apnoea that require bag and mask ventilation during the procedure [Time frame: 24 hours after procedure.]
  • Observed surfactant reflux [Time frame: 24 hours after procedure.]
  • Desaturation with SaO2 (right extremity measure) <85% during the procedure [Time frame: 24 hours after procedure.]
  • Procedural time consumption from the introduction of the laryngoscope blade into the oral cavity to removal of the catheter. [Time frame: 24 hours after procedure.]
  • Number of attempts of insertion of the catheter in the trachea. [Time frame: 24 hours after procedure.]
  • Number of attempts of insertion of the laryngoscope in the oral cavity. [Time frame: 24 hours after procedure.]
  • Time from meeting the criteria for surfactant treatment until surfactant administration [Time frame: 24 hours after procedure.]

Eligibility criteria

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 first-choice surfactant treatment by LISA as described by Sweet et al.: worsening babies with RDS and FiO2 > 0.30 on CPAP pressure ≥6 cm H2O.

Exclusion criteria

  • suspicion of lung hypoplasia,
  • endotracheal intubation at any time before randomisation,
  • suspicion of pneumothorax, pulmonary haemorrhage or pleural effusion before LISA,
  • major congenital anatomical anomalies as described by the European Surveillance of Congenital Anomalies (EUROCAT).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Quadruple blind
Primary purpose
Treatment

Study locations

Denmark · 4 centers
  • Neonatalafsnittet, Børn- og Ungeafdelingen, Reberbansgade 15 — Aalborg
  • Department of Paediatrics (Intensive Care Neonatology) and Perinatal Research Unit — Aarhus
  • Department of Neonatal and Pediatric Intensive Care, Blegdamsvej 9 — Copenhagen
  • H.C. Andersen Børne- og Ungehospital, Kløvervænget 23C, Indgang 60 — Odense

Publications

  • Breindahl N, Henriksen TB, Heiring C, Bay ET, Haaber J, Salmonsen TG, Carlsen ELM, Zachariassen G, Agergaard P, Viuff AF, Bender L, Gronnebaek Tolsgaard M, Aunsholt L. NON-pharmacological Approach Less Invasive Surfactant Administration (NONA-LISA) trial: protocol for a randomised controlled trial. Pediatr Res. 2024 Sep;96(4):1084-1089. doi: 10.1038/s41390-023-02998-0. Epub 2024 Jan 11. PMID 38200325
  • Breindahl N, Tolsgaard MG, Henriksen TB, Roehr CC, Szczapa T, Gagliardi L, Vento M, Stoen R, Bohlin K, van Kaam AH, Klotz D, Durrmeyer X, Han T, Katheria AC, Dargaville PA, Aunsholt L. Curriculum and assessment tool for less invasive surfactant administration: an international Delphi consensus study. Pediatr Res. 2023 Sep;94(3):1216-1224. doi: 10.1038/s41390-023-02621-2. Epub 2023 May 4. PMID 37142651
  • Breindahl N, Henriksen TB, Heiring C, Bay ET, Haaber J, Salmonsen TG, Agergaard P, Carlsen ELM, Tolsgaard MG, Aunsholt L. Can non-pharmacological comfort care replace fentanyl in LISA? The NONA-LISA feasibility study. Pediatr Res. 2026 Mar;99(4):1407-1414. doi: 10.1038/s41390-025-04310-8. Epub 2025 Aug 2. PMID 40753114

Identifiers

NCT: NCT05609877 · The NONA-LISA trial

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗