Respiratory Distress Syndrome in Premature InfantNONA-LISANCT05609877
The NONA-LISA Trial
A study testing Isotonic saline, Less Invasive Surfactant Administration (LISA) and Fentanyl in people with Respiratory Distress Syndrome in Premature Infant, run by Copenhagen University Hospital, Rigshospitalet at 4 sites in Denmark.
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… Read more about this study
- Who is it for?
- Ages 24 to 30 weeks
- Conditions the study is for
- Respiratory Distress Syndrome in Premature Infant
- What is being tested?
- Isotonic saline, Less Invasive Surfactant Administration (LISA) and Fentanyl
- Type of treatment
- Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 324 participants
- Where
- 4 sitesDenmark
- Study dates
- 1 Jun 2024to 31 May 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 30 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark4 sites, 3 recruiting
- Withdrawn
Neonatalafsnittet, Børn- og Ungeafdelingen, Reberbansgade 15
Aalborg, 9000
- Recruiting
Department of Paediatrics (Intensive Care Neonatology) and Perinatal Research Unit
Aarhus, 8200
Tine B Henriksen, MD, PhD, tine.brink.henriksen@clin.au.dk
Peter Agergaard, MD
- Recruiting
Department of Neonatal and Pediatric Intensive Care, Blegdamsvej 9
Copenhagen, 2100
Lise Aunsholt, MD, PhD, lise.aunsholt@regionh.dk
Niklas Breindahl, MD
- Not yet recruiting
H.C. Andersen Børne- og Ungehospital, Kløvervænget 23C, Indgang 60
Odense, 5000
Gitte Zachariassen, MD, PhD, Gitte.Zachariassen@rsyd.dk
Stine Lund, MD
About this study
Official title: NON-pharmacological Approach Less Invasive Surfactant Administration (NONA-LISA) Trial: Protocol for a Randomised Controlled Trial
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.
Read the 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.
- Being tested
- Isotonic saline, Less Invasive Surfactant Administration (LISA), Fentanyl, Non-pharmacological standard operating procedure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isotonic salineDrug
Isotonic saline will be administered intravenously instead of pre-procedure analgesia.
Less Invasive Surfactant Administration (LISA)Procedure or surgery
All infants will be treated with the Less Invasive Surfactant Administration (LISA) procedure
FentanylDrug
Fentanyl 0.5-1.0 mcg/kg will be administered intravenously as pre-procedure analgesia
Non-pharmacological standard operating procedureBehavioural
All infants will receive the same non-pharmacological standard operating procedure.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Isotonic saline; Procedure: Less Invasive Surfactant Administration (LISA); Behavioral: Non-pharmacological standard operating procedure |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours after procedure.
Secondary outcomes (27)
Incidence of additional fentanyl administration
This will include the number of injection(s), dosage, cumulated dose, and indications defined as pain/discomfort/sedation/other.
Measured: During the procedure, an average of 5-10 minutes.
Pain or discomfort during the procedure (according to COMFORTneo score >14).
This will include a numerical and a categorical variable (COMFORTneo score >/< 14).
Measured: 24 hours after procedure
Bradycardia <100 BPM for a minimum duration of 4 seconds.
This is a categorical variable (yes/no).
Measured: 24 hours after procedure.
Need for a second dose of surfactant
This is a categorical variable (yes/no).
Measured: 24 hours after procedure.
Escalation from LISA to INSURE in the same attempt
This is a categorical variable (yes/no).
Measured: 24 hours after procedure.
Apnoea that require bag and mask ventilation during the procedure
This is a categorical variable (yes/no).
Measured: 24 hours after procedure.
Observed surfactant reflux
This is a categorical variable (yes/no).
Measured: 24 hours after procedure.
Desaturation with SaO2 (right extremity measure) <85% during the procedure
This is a categorical variable (yes/no).
Measured: 24 hours after procedure.
Procedural time consumption from the introduction of the laryngoscope blade into the oral cavity to removal of the catheter.
This is a categorical variable (yes/no).
Measured: 24 hours after procedure.
Number of attempts of insertion of the catheter in the trachea.
This is a numerical variable.
Measured: 24 hours after procedure.
Number of attempts of insertion of the laryngoscope in the oral cavity.
This is a numerical variable.
Measured: 24 hours after procedure.
Time from meeting the criteria for surfactant treatment until surfactant administration
This is a numerical variable in minutes.
Measured: 24 hours after procedure.
Incidence of endotracheal intubation.
This is a categorical variable.
Measured: 48 hours after procedure
Incidence of pneumothorax within 48 hours after LISA.
This is a categorical variable.
Measured: 48 hours after procedure.
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).
This is a categorical variable.
Measured: 48 hours after procedure.
Incidence of in-hospital mortality before discharge.
This is a categorical variable.
Measured: Through study completion, an average of 6 months.
Cumulated duration of mechanical ventilation during hospitalisation.
This is a numerical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Cumulated duration of positive pressure ventilation during hospitalisation.
This is a numerical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Incidence of escalation of respiratory support from CPAP to other NIV modes during hospitalisation.
This is a categorical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Cumulated duration of all types of non-invasive respiratory support during hospitalisation.
This is a numerical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Cumulated duration of oxygen treatment with fraction of inspired oxygen (FiO2) >0.21.
This is a numerical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Cumulated duration of any repisratory support during hospitalisation.
This is a numerical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Duration of hospitalisation.
This is a numerical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Incidence of necrotising enterocolitis (according to Bell's Staging Criteria).
This is a categorical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Incidence of treatment-demanding retinopathy of prematurity.
This is a categorical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Incidence of intraventricular haemorrhage grade 3-4 and periventricular leukomalacia.
This is a categorical variable.
Measured: Before discharge (through study completion, an average of 6 months).
Composite outcome of death or moderate/severe BPD at 36 weeks of corrected gestational age.
This is a categorical variable.
Measured: 36 weeks of corrected gestational age.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2022
- Study start1 Jun 2024
- Primary completion31 May 2028 (estimated)
- Study completion31 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Respiratory Distress Syndrome in Premature InfantStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 324 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lise Aunsholt, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Niklas Breindahl, MD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05609877
- Sponsor's protocol ID
- The NONA-LISA trial
- Acronym
- NONA-LISA
- Status last verified
- Jul 2024
- First submitted
- 18 Oct 2022
- Last updated
- 20 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The datasets used and/or analysed during the current study will be available from the principal investigator on reasonable request after publication of results.
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.
PubMed 38200325Breindahl 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.
PubMed 37142651Breindahl 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.
PubMed 40753114
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NON-pharmacological Approach Less Invasive Surfactant Administration (NONA-LISA) Trial: Protocol for a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT05609877
- Acronym / sponsor ID
- NONA-LISA / The NONA-LISA trial
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 324 participants (estimated)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Study start
- 1 Jun 2024 (actual)
- Primary completion
- 31 May 2028 (estimated)
- Study completion
- 31 May 2029 (estimated)
- First posted
- 8 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Fentanyl group | Active comparator | Procedure: Less Invasive Surfactant Administration (LISA), Drug: Fentanyl, Behavioral: Non-pharmacological standard operating procedurePatients 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. |
| Saline group | Sham comparator | Drug: Isotonic saline, Procedure: Less Invasive Surfactant Administration (LISA), Behavioral: Non-pharmacological standard operating procedurePatients 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. |
Who may qualify
- Ages
- 24 to 30 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isotonic salineIsotonic saline will be administered intravenously instead of pre-procedure analgesia. | Drug | Saline group |
| Less Invasive Surfactant Administration (LISA)All infants will be treated with the Less Invasive Surfactant Administration (LISA) procedure | Procedure or surgery | Fentanyl group, Saline group |
| FentanylFentanyl 0.5-1.0 mcg/kg will be administered intravenously as pre-procedure analgesia | Drug | Fentanyl group |
| Non-pharmacological standard operating procedureAll infants will receive the same non-pharmacological standard operating procedure. | Behavioural | Fentanyl group, Saline group |
Primary outcome
LISA failure within 24 hours.
Time frame: 24 hours after procedure.
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.
27 secondary outcomes
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.
Incidence of endotracheal intubation.
Time frame: 48 hours after procedure
Incidence of pneumothorax within 48 hours after LISA.
Time frame: 48 hours after procedure.
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).
Time frame: 48 hours after procedure.
Incidence of in-hospital mortality before discharge.
Time frame: Through study completion, an average of 6 months.
Cumulated duration of mechanical ventilation during hospitalisation.
Time frame: Before discharge (through study completion, an average of 6 months).
Cumulated duration of positive pressure ventilation during hospitalisation.
Time frame: Before discharge (through study completion, an average of 6 months).
Incidence of escalation of respiratory support from CPAP to other NIV modes during hospitalisation.
Time frame: Before discharge (through study completion, an average of 6 months).
Cumulated duration of all types of non-invasive respiratory support during hospitalisation.
Time frame: Before discharge (through study completion, an average of 6 months).
Cumulated duration of oxygen treatment with fraction of inspired oxygen (FiO2) >0.21.
Time frame: Before discharge (through study completion, an average of 6 months).
Cumulated duration of any repisratory support during hospitalisation.
Time frame: Before discharge (through study completion, an average of 6 months).
Duration of hospitalisation.
Time frame: Before discharge (through study completion, an average of 6 months).
Incidence of necrotising enterocolitis (according to Bell's Staging Criteria).
Time frame: Before discharge (through study completion, an average of 6 months).
Incidence of treatment-demanding retinopathy of prematurity.
Time frame: Before discharge (through study completion, an average of 6 months).
Incidence of intraventricular haemorrhage grade 3-4 and periventricular leukomalacia.
Time frame: Before discharge (through study completion, an average of 6 months).
Composite outcome of death or moderate/severe BPD at 36 weeks of corrected gestational age.
Time frame: 36 weeks of corrected gestational age.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2024.
- Background: PubMed 38200325Breindahl 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.
- Background: PubMed 37142651Breindahl 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.
- Derived from this study: PubMed 40753114Breindahl 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.
- Individual participant dataSharing planned: No. The datasets used and/or analysed during the current study will be available from the principal investigator on reasonable request after publication of results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Niklas Breindahl, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Isotonic saline, Less Invasive Surfactant Administration (LISA) and Fentanyl in people with Respiratory Distress Syndrome in Premature Infant, run by Copenhagen University Hospital, Rigshospitalet at 4 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lise Aunsholt, MD, PhD (+4561991137, lise.aunsholt@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
LISA failure within 24 hours. (time frame: 24 hours after procedure.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05609877, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2024.