Surfactant Deficiency Syndrome NeonatalPhase 4LISA-MedNCT03735563
Premedication for Less Invasive Surfactant Administration
A Phase 4 study testing Ketamine and Fentanyl in people with Surfactant Deficiency Syndrome Neonatal, run by University of Oulu at 1 site in Finland.
Trial summary
Early respiratory management of preterm infants immediately after birth should be as gentle as possible. With this so-called developmental approach, unnecessary invasive methods can be avoided or at least postponed. This kind of "soft landing" allows cardiorespiratory transition with fewer adverse outcomes. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Surfactant Deficiency Syndrome Neonatal
- What is being tested?
- Ketamine and Fentanyl
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteFinland
- Study dates
- 11 Feb 2019to 31 Oct 2026
- Phase
- Phase 4
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Gestational age at birth ≥26 weeks
- Respiratory insufficiency managed with non-invasive respiratory support (nasal continuous positive airway pressure or high-flow)
- Requirement for oxygen to maintain oxygen saturation in the target range and need for surfactant treatment (according to clinician's assessment)
- If further doses of surfactant are needed, patient can be re-randomized
Who cannot join
- Severe RDS with high oxygen requirements, severe respiratory acidosis and/or widespread atelectasis radiologically, such that ongoing ventilator support will be necessary after surfactant therapy (intubation in preferable to LISA if FiO2 >40% at GA <28 weeks and >60% at GA ≥28 weeks)
- Maxillo-facial, tracheal or known pulmonary malformations
- Any known chromosomal abnormality or severe malformation
- An alternative cause for respiratory distress (e.g. congenital pneumonia or pulmonary hypoplasia)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Finland1 site, 1 recruiting
- Recruiting
Oulu University Hospital
Oulu
Eveliina Ronkainen, MD, PhD
About this study
Early respiratory management of preterm infants immediately after birth should be as gentle as possible. With this so-called developmental approach, unnecessary invasive methods can be avoided or at least postponed. This kind of "soft landing" allows cardiorespiratory transition with fewer adverse outcomes. Less invasive surfactant administration (LISA) is a technique that involves delivery of surfactant to a spontaneously breathing infant through a thin catheter. This technique minimizes the risk for neonatal lung injury caused by positive pressure ventilation. LISA is nowadays widely used in neonatal intensive care units (NICU). Although less invasive, newborns exposed to this procedure need premedication prior the procedure. There is no consensus, which drug would be the optimal premedication for LISA and the research on this topic is lacking. An ideal premedication would treat the procedural pain without suppressing the infant's own breathing. The sedation and analgesia should start fast but the effect should be short-acting with as few adverse effects as possible. The aim of this randomized, controlled trial (RCT) is to evaluate the feasibility, efficacy and safety of LISA protocol with the premedication of either ketamine or fentanyl by investigating whether one or the other is associated with lower rate of adverse events, hence would be preferred choice for premedication protocol.
Read the detailed description
All infants fulfilling the inclusion criteria during the study period are asked to participate in this randomized controlled trial of LISA premedication. Written informed parental consent is acquired from all of the participants. After the consent, individuals needing the LISA will receive premedication as follows: caffeine (in case of gestational age <32 weeks and not already given), glycopyrrolate, and randomly either ketamine or fentanyl. The investigators and medical staff are blinded to the fact which study medication is given. This study is a pilot study and 20 patients are recruited for both groups. Randomization is done in the blocks of four.
S-ketamine (Ketanest-S 5 mg/ml) or fentanyl (Fentanyl-Hamel diluted to 5 μg/ml) is used as a masked study drug. Both study drug solutions appear equally transparent. Drug administration is started with glucopyrrolate (Robinul 0.2 mg/ml), which is given intravenously at a dose of 5 µg/kg. Thereafter, the masked study drug is administered intravenously slowly in one to two minute injection of 0.2 ml/kg. In this way, doses of S-ketamine 1 mg/kg or alternatively fentanyl 1 μg/kg is received. After five minutes (from the beginning of administration of the study drug), videolaryngoscopy is started. If the study drug does not have sufficient effect, the study drug may be repeated with the same dose. If study drug fails to give appropriate conditions to LISA procedure, midazolam 0,1 mg/kg can be used as an additional drug.
- Conditions
- Surfactant Deficiency Syndrome Neonatal
- Keywords
- less invasive surfactant administration, premedication
- Medical subject headings
- Pulmonary Atelectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketanest-S
Individuals will receive randomly either ketamine or fentanyl as a premedication
FentanylDrug
Also called Fentanyl-Hamel
Individuals will receive randomly either ketamine or fentanyl as a premedication
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Individuals needing the LISA will receive premedication as follows: caffeine (in case of gestational age <32 weeks and not already given), glycopyrrolate, and randomly either ketamine or fentanyl. Receives: Drug: Ketamine |
| Fentanyl | Experimental | Individuals needing the LISA will receive premedication as follows: caffeine (in case of gestational age <32 weeks and not already given), glycopyrrolate, and randomly either ketamine or fentanyl. Receives: Drug: Fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event
The need of positive pressure ventilation (PPV), intubation, heart rate below 80 per minute, mean arterial pressure change more than 20%, pH change more than 0.4, and CO2 change more than 20%, and saturation <85 for more than 1 minute
Measured: 1 hour
Secondary outcomes (5)
Duration of the procedure
Duration of the procedure is evaluated retrospectively from the recording of the videolaryngoscopy (an attempt begins when the laryngoscope enters the mouth and ends with LISACath in the trachea)
Measured: 1 hour
Number of attempts to get the catether intratracheally
Number of attempts to get the catether intratracheally is evaluated retrospectively from the recording of the videolaryngoscopy (one laryngoscopy = one attempt)
Measured: 1 hour
Pain score NIAPAS
Pain will be scored with validated Neonatal Infant Acute Pain Assessment Scale (NIAPAS) tool. The scale includes five behavioral and three physiological indicators, and takes into account the gestational age of neonates as a contextual factor. The indicators are rated on a 2, 3, or 4-point scale for a possible total score of 18. Assessments of each neonate include alertness, facial expressions, crying, muscle tension, reaction to handling, and breathing. In addition, the neonates on monitors are assessed for changes in heart rate and oxygen saturation (Copyright Pölkki T, Korhonen A, Axelin A. 2013)
Measured: 1 hour
The need for additional dosing of study drug or midazolam (number of addtional dosages)
If the study drug does not have sufficient effect, the study drug may be repeated with the same dose. If study drug fails to give appropriate conditions to LISA procedure, midazolam 0,1 mg/kg can be used as an additional drug.
Measured: 1 hour
Edi-signals
Special Edi (Electronic Diaphragm Monitoring) Catheter is placed to read the electrical activity of the diaphragm. Edi min and Edi max in different time points will be collected.
Measured: 1 hour
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2018
- Study start11 Feb 2019
- Primary completion31 Oct 2025 (estimated)
- Study completion31 Oct 2026 (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 Surfactant Deficiency Syndrome NeonatalStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oulu
- Sponsor type
- University, hospital or other
- Collaborators
- Oulu University Hospital
- Responsible party
- Sponsor
- Investigators
- Riitta Marttila, MD, docent, Principal investigator, Oulu University and Oulu University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03735563
- Sponsor's protocol ID
- OY062018
- Acronym
- LISA-Med
- Status last verified
- Jun 2023
- First submitted
- 7 Nov 2018
- Last updated
- 5 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GH, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology. 2017;111(2):107-125. doi: 10.1159/000448985. Epub 2016 Sep 21.
PubMed 27649091Vento M, Dargaville P, Bohlin K, Herting E & Roehr C LISA Training Advisory Board Report.
Polkki T, Korhonen A, Axelin A, Saarela T, Laukkala H. Development and preliminary validation of the Neonatal Infant Acute Pain Assessment Scale (NIAPAS). Int J Nurs Stud. 2014 Dec;51(12):1585-94. doi: 10.1016/j.ijnurstu.2014.04.001. Epub 2014 Apr 18.
PubMed 24815773
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Premedication for Less Invasive Surfactant Administration
- ClinicalTrials.gov ID
- NCT03735563
- Acronym / sponsor ID
- LISA-Med / OY062018
- Conditions
- Surfactant Deficiency Syndrome Neonatal
- Keywords
- less invasive surfactant administration, premedication
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of OuluUniversity, hospital or other
- Collaborators
- Oulu University Hospital
- Study start
- 11 Feb 2019 (actual)
- Primary completion
- 31 Oct 2025 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 8 Nov 2018 (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.
Early respiratory management of preterm infants immediately after birth should be as gentle as possible. With this so-called developmental approach, unnecessary invasive methods can be avoided or at least postponed. This kind of "soft landing" allows cardiorespiratory transition with fewer adverse outcomes. Less invasive surfactant administration (LISA) is a technique that involves delivery of surfactant to a spontaneously breathing infant through a thin catheter. This technique minimizes the risk for neonatal lung injury caused by positive pressure ventilation. LISA is nowadays widely used in neonatal intensive care units (NICU). Although less invasive, newborns exposed to this procedure need premedication prior the procedure. There is no consensus, which drug would be the optimal premedication for LISA and the research on this topic is lacking. An ideal premedication would treat the procedural pain without suppressing the infant's own breathing. The sedation and analgesia should start fast but the effect should be short-acting with as few adverse effects as possible. The aim of this randomized, controlled trial (RCT) is to evaluate the feasibility, efficacy and safety of LISA protocol with the premedication of either ketamine or fentanyl by investigating whether one or the other is associated with lower rate of adverse events, hence would be preferred choice for premedication protocol.
Detailed description
All infants fulfilling the inclusion criteria during the study period are asked to participate in this randomized controlled trial of LISA premedication. Written informed parental consent is acquired from all of the participants. After the consent, individuals needing the LISA will receive premedication as follows: caffeine (in case of gestational age <32 weeks and not already given), glycopyrrolate, and randomly either ketamine or fentanyl. The investigators and medical staff are blinded to the fact which study medication is given. This study is a pilot study and 20 patients are recruited for both groups. Randomization is done in the blocks of four.
S-ketamine (Ketanest-S 5 mg/ml) or fentanyl (Fentanyl-Hamel diluted to 5 μg/ml) is used as a masked study drug. Both study drug solutions appear equally transparent. Drug administration is started with glucopyrrolate (Robinul 0.2 mg/ml), which is given intravenously at a dose of 5 µg/kg. Thereafter, the masked study drug is administered intravenously slowly in one to two minute injection of 0.2 ml/kg. In this way, doses of S-ketamine 1 mg/kg or alternatively fentanyl 1 μg/kg is received. After five minutes (from the beginning of administration of the study drug), videolaryngoscopy is started. If the study drug does not have sufficient effect, the study drug may be repeated with the same dose. If study drug fails to give appropriate conditions to LISA procedure, midazolam 0,1 mg/kg can be used as an additional drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineIndividuals needing the LISA will receive premedication as follows: caffeine (in case of gestational age <32 weeks and not already given), glycopyrrolate, and randomly either ketamine or fentanyl. |
| Fentanyl | Experimental | Drug: FentanylIndividuals needing the LISA will receive premedication as follows: caffeine (in case of gestational age <32 weeks and not already given), glycopyrrolate, and randomly either ketamine or fentanyl. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Gestational age at birth ≥26 weeks
- Respiratory insufficiency managed with non-invasive respiratory support (nasal continuous positive airway pressure or high-flow)
- Requirement for oxygen to maintain oxygen saturation in the target range and need for surfactant treatment (according to clinician's assessment)
- If further doses of surfactant are needed, patient can be re-randomized
Key exclusion criteria (4 listed)
- Severe RDS with high oxygen requirements, severe respiratory acidosis and/or widespread atelectasis radiologically, such that ongoing ventilator support will be necessary after surfactant therapy (intubation in preferable to LISA if FiO2 >40% at GA <28 weeks and >60% at GA ≥28 weeks)
- Maxillo-facial, tracheal or known pulmonary malformations
- Any known chromosomal abnormality or severe malformation
- An alternative cause for respiratory distress (e.g. congenital pneumonia or pulmonary hypoplasia)
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 |
|---|---|---|
| KetamineAlso: Ketanest-SIndividuals will receive randomly either ketamine or fentanyl as a premedication | Drug | Ketamine |
| FentanylAlso: Fentanyl-HamelIndividuals will receive randomly either ketamine or fentanyl as a premedication | Drug | Fentanyl |
Primary outcome
Adverse event
Time frame: 1 hour
The need of positive pressure ventilation (PPV), intubation, heart rate below 80 per minute, mean arterial pressure change more than 20%, pH change more than 0.4, and CO2 change more than 20%, and saturation <85 for more than 1 minute
5 secondary outcomes
Duration of the procedure
Time frame: 1 hour
Number of attempts to get the catether intratracheally
Time frame: 1 hour
Pain score NIAPAS
Time frame: 1 hour
The need for additional dosing of study drug or midazolam (number of addtional dosages)
Time frame: 1 hour
Edi-signals
Time frame: 1 hour
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 5 Jun 2023.
- Background: PubMed 27649091Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Plavka R, Saugstad OD, Simeoni U, Speer CP, Vento M, Visser GH, Halliday HL. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2016 Update. Neonatology. 2017;111(2):107-125. doi: 10.1159/000448985. Epub 2016 Sep 21.
- BackgroundVento M, Dargaville P, Bohlin K, Herting E & Roehr C LISA Training Advisory Board Report.
- Background: PubMed 24815773Polkki T, Korhonen A, Axelin A, Saarela T, Laukkala H. Development and preliminary validation of the Neonatal Infant Acute Pain Assessment Scale (NIAPAS). Int J Nurs Stud. 2014 Dec;51(12):1585-94. doi: 10.1016/j.ijnurstu.2014.04.001. Epub 2014 Apr 18.
- Individual participant dataSharing planned: No
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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.
Riitta Marttila, MD, docent principal investigator
Oulu University and Oulu University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine and Fentanyl in people with Surfactant Deficiency Syndrome Neonatal, run by University of Oulu at 1 site in Finland.
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 4 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 5 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Eveliina Ronkainen, MD, PhD (+358 8 3152011, eveliina.ronkainen@oulu.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse event (time frame: 1 hour). 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 NCT03735563, 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 5 Jun 2023.