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

NCT ID: NCT04016246

Last Updated: 2024-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

233 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-07

Study Completion Date

2026-10-31

Brief Summary

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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.

Detailed Description

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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). 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.

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.

Conditions

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Respiratory Distress Syndrome in Premature Infant

Keywords

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LISA propofol medialipide ketamin sedation premature infant surfactant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Propofol

Propofol (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. If the FANS score is ≥6, 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. (See paragraph 5.3)

Group Type EXPERIMENTAL

Propofol-Lipuro

Intervention Type DRUG

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

medialipide

Name 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

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

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

Interventions

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Propofol-Lipuro

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

Intervention Type DRUG

Placebos

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

Intervention Type DRUG

Other Intervention Names

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medialipide

Eligibility Criteria

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Inclusion Criteria

* 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)

* 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

Exclusion Criteria

* 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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Grenoble

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thierry DEBILLON, MD PHD

Role: PRINCIPAL_INVESTIGATOR

CHU de Grenoble Alpes

Locations

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centre hospitalier deTroyes

Troyes, aube, France

Site Status

CHU Grenoble Alpes

Grenoble, Isère, France

Site Status

Chu Amiens

Amiens, , France

Site Status

Chu Angers

Angers, , France

Site Status

Chu Brest

Brest, , France

Site Status

Chu Chambery

Chambéry, , France

Site Status

Chi Creteil

Créteil, , France

Site Status

Chu Limoges

Limoges, , France

Site Status

Ap-H Marseille

Marseille, , France

Site Status

Chu Nantes

Nantes, , France

Site Status

Chu Nimes

Nîmes, , France

Site Status

Chi Poissy St Germain

Poissy, , France

Site Status

Ch Rennes

Rennes, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 26907795 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25164872 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21963186 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30068669 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22250028 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29532502 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17485450 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26922562 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23439457 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23359581 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28483817 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27942865 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32384914 (View on PubMed)

Other Identifiers

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38RC18.123

Identifier Type: -

Identifier Source: org_study_id