The NONA-LISA Trial

NCT05609877 | Recruiting DMC

• 1 other identifier: The NONA-LISA trial
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Respiratory Distress Syndrome in Premature Infant

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (27)

• Incidence of additional fentanyl administration

  During the procedure, an average of 5-10 minutes.

• Pain or discomfort during the procedure (according to COMFORTneo score >14).

  24 hours after procedure

• Bradycardia <100 BPM for a minimum duration of 4 seconds.

  24 hours after procedure.

• Need for a second dose of surfactant

  24 hours after procedure.

• Escalation from LISA to INSURE in the same attempt

  24 hours after procedure.

Study Arms (2)

Fentanyl group

ACTIVE COMPARATOR

Patients will receive 0.5-1 mcg/kg fentanyl intravenously as pre-procedure analgesia for Less Invasive Surfactant Administration (LISA). The staff will perform LISA using standard pre- and post-procedure care, including non-pharmacological treatment and the use of atropine, caffeine, and naloxone at the clinician's discretion, based on local protocols and guidelines. All medications will be registered.

Procedure: Less Invasive Surfactant Administration (LISA); Drug: Fentanyl; Behavioral: Non-pharmacological standard operating procedure

Saline group

SHAM COMPARATOR

Patients will receive a placebo (isotonic saline) instead of pre-procedure analgesia for Less Invasive Surfactant Administration (LISA). The staff will perform LISA using standard pre- and post-procedure care, including non-pharmacological treatment and the use of atropine, caffeine, and naloxone at the clinician's discretion, based on local protocols and guidelines. All medications will be registered.

Drug: Isotonic saline; Procedure: Less Invasive Surfactant Administration (LISA); Behavioral: Non-pharmacological standard operating procedure

Interventions

Isotonic saline DRUG

Isotonic saline will be administered intravenously instead of pre-procedure analgesia.

Saline group

Less Invasive Surfactant Administration (LISA) PROCEDURE

All infants will be treated with the Less Invasive Surfactant Administration (LISA) procedure

Fentanyl group; Saline group

Fentanyl DRUG

Fentanyl 0.5-1.0 mcg/kg will be administered intravenously as pre-procedure analgesia

Fentanyl group

Non-pharmacological standard operating procedure BEHAVIORAL

All infants will receive the same non-pharmacological standard operating procedure.

Fentanyl group; Saline group

Eligibility Criteria

• Age: 24 Weeks - 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (4)

Neonatalafsnittet, Børn- og Ungeafdelingen, Reberbansgade 15

Aalborg, 9000, Denmark

WITHDRAWN

Department of Paediatrics (Intensive Care Neonatology) and Perinatal Research Unit

Aarhus, 8200, Denmark

RECRUITING

Department of Neonatal and Pediatric Intensive Care, Blegdamsvej 9

Copenhagen, 2100, Denmark

RECRUITING

H.C. Andersen Børne- og Ungehospital, Kløvervænget 23C, Indgang 60

Odense, 5000, Denmark

NOT YET RECRUITING

Related Publications (3)

• 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 BACKGROUND

• 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 BACKGROUND

• 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. 2025 Aug 2. doi: 10.1038/s41390-025-04310-8. Online ahead of print.

  PMID: 40753114 DERIVED

MeSH Terms

Interventions

Sodium Chloride; Fentanyl

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Niklas Breindahl, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Aunsholt, MD, PhD

CONTACT

+4561991137; lise.aunsholt@regionh.dk

Niklas Breindahl, MD

CONTACT

+4528566410; niklas.breindahl@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, care provider, investigator and outcomes assessor will initially be blinded to treatment with analgesia or placebo (isotonic saline solution). Need for additional doses of analgesia will be decided according to section "Interventions" and will not be blinded. To reduce risk of interpretation bias, primary analyses will be performed blinded to the group allocation (Group A compared with Group B) and will be presented to all authors, who will agree on two alternative written interpretations before the randomisation code will be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, associate professor

Model Details: 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).

Study Record Dates

• First Submitted: October 18, 2022
• First Posted: November 8, 2022
• Study Start: June 1, 2024
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2029
• Last Updated: September 20, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (4)