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Respiratory Distress Syndrome in Premature InfantPhase 3PROLISANCT04016246

Respiratory Effect of the LISA Method With Sedation by Propofol Versus Absence of Sedation.

A Phase 3 study testing Propofol-Lipuro in people with Respiratory Distress Syndrome in Premature Infant, run by University Hospital, Grenoble at 13 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The investigators propose to evaluate premedication with Propofol compared to a control strategy including a placebo with a possible rescue treatment with ketamine to ensure pain control before LISA Procedure . Read more about this study

Who is it for?
Any age
What is being tested?
Propofol-Lipuro
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
233 participants
Where
13 sitesFrance
Study dates
7 Oct 2019to 30 Apr 2026
Phase
Phase 3
Are there results?
None posted in the registry

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

  • Preterm Infants < 32 wGA (weeks of gestational age)
  • Presenting a RDS (respiratory distress syndrome)
  • in the first 48 hours of life
  • treated by CPAP (continuous positive airway pressure) or BiPAP (Bilevel Positive Airway Pressure)
  • requiring surfactant :
  • FIO2 : (fraction of inspired oxygen)
Show all 12Show fewer
  • if 28 - 31 SA : FiO2 ≥30% for a duration ≥ 10mn
  • if <28 SA FIO2 ≥25% for a duration ≥10mn
  • SpO2 (arterial oxygen saturation) : to obtain a SpO2 between ≥88 and ≤ 95%
  • Available IntraVenous line (peripheral, umbilical or central catheter)
  • Recipient of the French Social Security
  • Informed consent form signed

Who cannot join

  • Congenital and/or major malformations
  • FIO2 >60%
  • Silverman score >6
  • Contraindication to the use of Propofol :
  • Low Blood Pressure with 2 successive measurements (Mean < Gestational Age expressed in Weeks of Gestation) persisting after one volume expansion,
  • Use of inotropic medication to maintain a normal blood pressure.
  • Use of sedative or analgesic drugs (except paracetamol and ibuprofen) in the previous 24h
  • Coma, convulsions, areactivity at neurological examination

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

France13 sites

  • Chu Amiens

    Amiens, 80000

  • Chu Angers

    Angers, 49000

  • Chu Brest

    Brest, 29200

  • Chu Chambery

    Chambéry, 73000

  • Chi Creteil

    Créteil, 94000

  • CHU Grenoble Alpes

    Grenoble, Isère, 38043

  • Chu Limoges

    Limoges, 87000

  • Ap-H Marseille

    Marseille, 13000

  • Chu Nantes

    Nantes, 44000

  • Chu Nimes

    Nîmes, 30000

  • Chi Poissy St Germain

    Poissy, 78300

  • Ch Rennes

    Rennes, 35000

  • centre hospitalier deTroyes

    Troyes, Aube, 10000

Other trials in France

About this study

Official title: Respiratory Effect of the LISA (Less Invasive Surfactant Administration) Method With Sedation by Propofol Versus Absence of Sedation: Double-blind Comparative Randomized Clinical Trial.

The investigators propose to evaluate premedication with Propofol compared to a control strategy including a placebo with a possible rescue treatment with ketamine to ensure pain control before LISA Procedure . Investigators hypothesize that sedation with Propofol is safe and non-inferior to placebo for the risk of Mechanical Ventilation in the 72 hours following the procedure.

Read the detailed description

Non-inferiority trial comparing Propofol versus placebo during the intra tracheal Less Invasive Surfactant Administration (LISA) in preterm babies < 32 weeks of gestation for the need for mechanical ventilation after the procedure. An open-label ketamine treatment as rescue is possible in each group.

In each participating unit, information will be given to parents of preterm babies <32 wGA upon their admission to the delivery room or to the NICU (neonatal intensive care unit), and informed consent will be sought as soon as possible. Eligible babies presenting a RDS (respiratory distress syndrome) will be included and randomized to the control (placebo) group or Propofol group. While benefiting from Nasal Intermittent Positive Pressure Ventilation (NIPPV) the newborn will be prepared as usual for tracheal intubation. Trialists will be blinded to treatment allocation.

The drug administration in the two groups will be titrated according to weight (0.5mg/kg per dose of Propofol or a similar volume of placebo). Before and after each dose, a pain score (FANS) will be quickly evaluated within 2 minutes of the injection, to assess the need for a supplementary dose (up to a predefined limit) or rescue treatment by Ketamine, also according to the clinician's clinical impression .

After the steps of sedation, the LISA procedure will be performed, with detailed data collection of per procedure events up to 72 hours of life. Babies will be subsequently managed as usual in each NICU and data will be collected about respiratory, neurological and hemodynamic outcomes during the hospital stay, and especially at discharge, 28 days, and 36 weeks. At two years of corrected age, a final examination will be performed to evaluate neurodevelopmental outcomes.

Being tested
Propofol-Lipuro, Placebos
Keywords
LISA, propofol, medialipide, ketamin, sedation, premature infant, surfactant
Medical subject headings
Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Propofol-LipuroDrug

    sedation of babies < 32wGA with propofol / placebo before a LISA Procedure

  • PlacebosDrug

    Also called medialipide

    injected to babies < 32wGA with propofol / placebo before a LISA Procedure

Study groups in NCT04016246
Study groupRoleWhat they receive
PropofolExperimentalPropofol (Propofol LIPURO 1% 100mL), Pharmacologic form: 10mg/ml. Considering the birthweight of most preterm babies, Propofol will be diluted to a final concentration of 1mg/ml by the nurse. Treatment initiation: the 1st dose will be injected following usual management of LISA procedure included the installation of the newborn and the atropine and caffeine injections and sugar solution administration Dose per administration: 0.5mg/kg per dose of Propofol. Number of administrations: Several administrations of 0.5 mg/kg are possible, according the level of sedation achieved, as evaluated by the FANS score and the physician feeling. If the FANS score is ≥6 AND the baby is not comfortable, a new dose will be injected up to a total of two (before 28 wGA) or 3 (between 28 - 31 wGA) administrations of the drug.
Receives: Drug: Propofol-Lipuro
medialipidePlacebo comparatorName of treatment for placebo: Medialipide® (B. BRAUN) Pharmacological form: 20g/100ml Medialipide 20% will be used as the placebo. This is an emulsion of medium and long triglycerides based on soya oil and having same appearance organoleptic characteristics as Propofol. Dose per administration: Same volume as for the Propofol administration Number of administrations: according the same protocol that for the Propofol administration. Modalities of preparation : The same dilution procedure as Propofol lipuro 1% SPC (Summary of Product Characteristics):1 part of Medialipide 20% with 9 parts of 5% w/v glucose solution or 0.9% w/v sodium chloride solution as shown in parenteral nutrition which is in accordance with medialipide 20% SPC
Receives: Drug: Placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. need for mechanical ventilation after the procedure

    Rate of mechanical ventilation from the start of the LISA procedure up to 72 hours of life Pain before procedure (need of ketamine administration) or within 1 hour following first injection of propofol/placebo (FANS score ≥ 6)

    Measured: 72hours

Secondary outcomes (20)

  1. Rate of MV (mechanical ventilation ) in each class of GA (<28, 28-31wGA)

    Rate of MV (mechanical ventilation

    ) from the start of the LISA procedure up to 72 hours of life in each class of GA (<28, 28-31wGA)

    Measured: 72hours

  2. FANS during LISA and 1h after LISA

    Faceless acute neonatal pain scale (FANS) assessed during LISA and 1 hour after the procedure by an independent operator.

    Measured: 1hour

  3. number of ketamine administrations for rescue

    Number of ketamine administrations for rescue in order to obtain a FANS score <6 and to be able to proceed to LISA.

    Measured: before LISA Procedure

  4. Number of laryngoscopies

    Number of laryngoscopies needed to perform LISA

    Measured: during LISA Procedure (T0)

  5. Tolerance and efficacy (Per procedure events): Apnea

    Apnea requiring bag mask ventilation

    Measured: during LISA Procedure (T0)

  6. Tolerance and efficacy (Per procedure events): emergency intubation

    Emergency intubation after the drug injection before the LISA procedure can be performed or within 1h following the drug injection

    Measured: from drug injection to 1hour after

  7. Tolerance and efficacy (Per procedure events): Viby Mogensen score

    Clinician's satisfaction during laryngoscopy with the Viby Mogensen score :

    Item Score 1 Score 2 Score 3 Score 4 Laryngoscopy Easy Fair Difficult Impossible Vocal cords Open Moving Closing Closed Coughing None Slight Moderate Severe Jaw relaxation Complete Slight Stiff Rigid Limb movements None Slight Moderate Severe

    the total score is calculated adding each item scores. min score = 5. max score = 20. An easy intubation would obtain a low score and a difficult intubation would have a high score.

    Measured: during LISA Procedure

  8. BPD (bronchopulmonary dysplasia) at 36 weeks of Gestational Age

    Broncho Pulmonary Dysplasia at 36 weeks of Gestational Age

    Measured: equivalent to 36 weeks of Gestational Age

  9. In-hospital morbidity and mortality: pneumothorax

    Pneumothorax within 72hours

    Measured: 72hours post LISA Procedure

  10. In-hospital morbidity and mortality: Necrotizing Enterocolitis

    necrotizing enterocolitis during hospitalization

    Measured: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age)

  11. In-hospital morbidity and mortality : sepsis

    proven sepsis during hospitalization

    Measured: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age)

  12. In-hospital morbidity and mortality: retinopathy

    retinopathy of prematurity during hospitalization

    Measured: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of gestational ageGA)

  13. In-hospital morbidity and mortality

    periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage during hospitalization

    Measured: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of Gestational Age)

  14. In-hospital morbidity and mortality: patent ductus arteriosus

    treatment of a patent ductus arteriosus during hospitalization

    Measured: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age)

  15. In-hospital morbidity and mortality: death 36weeks of Gestational Age

    Death at 36 weeks of Gestational Age

    Measured: equivalent to 36 weeks of Gestational Age

  16. In-hospital morbidity and mortality: death during hospitalization

    in-hospital mortality

    Measured: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of Gestational Age)

  17. At two years of corrected age: ASQ (Ages and Stages Questionnaire)

    ASQ (Ages and Stages Questionnaire) questionnaire is a general developmental screening tool (5 areas are evaluated: Communication, gross motor, fine motor, problem solving, and personal-social). Total score is the sum of each of the 5 area scores (wich are between 0-60. Total score is between 0 and 300. The higher the score is, the best developed the children is.

    Measured: 2 years (corrected age)

  18. At two years of corrected age: motor function

    Gross Motor Function Classification Scale (GMFCS) looks at movements such as sitting, walking and use of mobility devices. It is helpful because it provides families and clinicians with a clear description of a child's current motor function, and an idea of what equipment or mobility aids a child may need in the future, e.g. crutches, walking frames or wheelchairs.

    Participant will be assignated to one of the 5 levels by the clinicians : a patient who is in level 5 has more motor impairments than a patient in level 1.

    Measured: 2 years (corrected age)

  19. At two years of corrected age: vision

    Visual functions : a clinical examination will conclude if the participant has a visual deficit or not. And in the deficit case, what kind of vision pathology.

    Measured: 2 years (corrected age)

  20. At two years of corrected age: audition

    Hearing functions : a clinical examination will conclude if the participant has a hearing deficit or not. And in the deficit case, what kind of audition pathology.

    Measured: 2 years (corrected age)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2019
  2. Study start7 Oct 2019
  3. Primary completion18 Mar 2024
  4. Study completion30 Apr 2026

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
233 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04016246
Sponsor's protocol ID
38RC18.123
Acronym
PROLISA
Status last verified
May 2026
First submitted
7 Jun 2019
Last updated
9 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Chevallier M, Durrmeyer X, Ego A, Debillon T; PROLISA Study Group. Propofol versus placebo (with rescue with ketamine) before less invasive surfactant administration: study protocol for a multicenter, double-blind, placebo controlled trial (PROLISA). BMC Pediatr. 2020 May 8;20(1):199. doi: 10.1186/s12887-020-02112-x.

    PubMed 32384914

  • Dekker J, Lopriore E, Rijken M, Rijntjes-Jacobs E, Smits-Wintjens V, Te Pas A. Sedation during Minimal Invasive Surfactant Therapy in Preterm Infants. Neonatology. 2016;109(4):308-13. doi: 10.1159/000443823. Epub 2016 Feb 24.

    PubMed 26907795

  • Dargaville PA, Kamlin CO, De Paoli AG, Carlin JB, Orsini F, Soll RF, Davis PG. The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation. BMC Pediatr. 2014 Aug 27;14:213. doi: 10.1186/1471-2431-14-213.

    PubMed 25164872

  • Gopel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C, Siegel J, Avenarius S, von der Wense A, Vochem M, Groneck P, Weller U, Moller J, Hartel C, Haller S, Roth B, Herting E; German Neonatal Network. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet. 2011 Nov 5;378(9803):1627-34. doi: 10.1016/S0140-6736(11)60986-0. Epub 2011 Sep 29.

    PubMed 21963186

  • Dekker J, Lopriore E, van Zanten HA, Tan RNGB, Hooper SB, Te Pas AB. Sedation during minimal invasive surfactant therapy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019 Jul;104(4):F378-F383. doi: 10.1136/archdischild-2018-315015. Epub 2018 Aug 1.

    PubMed 30068669

  • Berde CB, Walco GA, Krane EJ, Anand KJ, Aranda JV, Craig KD, Dampier CD, Finkel JC, Grabois M, Johnston C, Lantos J, Lebel A, Maxwell LG, McGrath P, Oberlander TF, Schanberg LE, Stevens B, Taddio A, von Baeyer CL, Yaster M, Zempsky WT. Pediatric analgesic clinical trial designs, measures, and extrapolation: report of an FDA scientific workshop. Pediatrics. 2012 Feb;129(2):354-64. doi: 10.1542/peds.2010-3591. Epub 2012 Jan 16.

    PubMed 22250028

  • Bourgoin L, Caeymaex L, Decobert F, Jung C, Danan C, Durrmeyer X. Administering atropine and ketamine before less invasive surfactant administration resulted in low pain scores in a prospective study of premature neonates. Acta Paediatr. 2018 Jul;107(7):1184-1190. doi: 10.1111/apa.14317. Epub 2018 Apr 16.

    PubMed 29532502

  • Ghanta S, Abdel-Latif ME, Lui K, Ravindranathan H, Awad J, Oei J. Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: a randomized, controlled trial. Pediatrics. 2007 Jun;119(6):e1248-55. doi: 10.1542/peds.2006-2708. Epub 2007 May 7.

    PubMed 17485450

  • Owen LS, Manley BJ. Nasal intermittent positive pressure ventilation in preterm infants: Equipment, evidence, and synchronization. Semin Fetal Neonatal Med. 2016 Jun;21(3):146-53. doi: 10.1016/j.siny.2016.01.003. Epub 2016 Feb 26.

    PubMed 26922562

  • Durrmeyer X, Daoud P, Decobert F, Boileau P, Renolleau S, Zana-Taieb E, Saizou C, Lapillonne A, Granier M, Durand P, Lenclen R, Coursol A, Nicloux M, de Saint Blanquat L, Shankland R, Boelle PY, Carbajal R. Premedication for neonatal endotracheal intubation: results from the epidemiology of procedural pain in neonates study. Pediatr Crit Care Med. 2013 May;14(4):e169-75. doi: 10.1097/PCC.0b013e3182720616.

    PubMed 23439457

  • Kanmaz HG, Erdeve O, Canpolat FE, Mutlu B, Dilmen U. Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial. Pediatrics. 2013 Feb;131(2):e502-9. doi: 10.1542/peds.2012-0603. Epub 2013 Jan 28.

    PubMed 23359581

  • Descamps CS, Chevallier M, Ego A, Pin I, Epiard C, Debillon T. Propofol for sedation during less invasive surfactant administration in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2017 Sep;102(5):F465. doi: 10.1136/archdischild-2017-312791. Epub 2017 May 8. No abstract available.

    PubMed 28483817

  • Klotz D, Porcaro U, Fleck T, Fuchs H. European perspective on less invasive surfactant administration-a survey. Eur J Pediatr. 2017 Feb;176(2):147-154. doi: 10.1007/s00431-016-2812-9. Epub 2016 Dec 9.

    PubMed 27942865

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Propofol-Lipuro in people with Respiratory Distress Syndrome in Premature Infant, run by University Hospital, Grenoble at 13 sites in France.

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 12 inclusion and 8 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: finished, as of the sponsor's last update on 9 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in France. 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

need for mechanical ventilation after the procedure (time frame: 72hours). 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 NCT04016246, which also lists 13 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 9 Jun 2026.

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