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

NCT04016246 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: 38RC18.123
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 13

Brief 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 . 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.

Conditions

Respiratory Distress Syndrome in Premature Infant

Keywords

LISA; propofol; medialipide; ketamin; sedation; premature infant; surfactant

Outcome Measures

Primary Outcomes (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.

  72hours

Secondary Outcomes (20)

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

  72hours

• FANS during LISA and 1h after LISA

  1hour

• number of ketamine administrations for rescue

  before LISA Procedure

• Number of laryngoscopies

  during LISA Procedure (T0)

• Tolerance and efficacy (Per procedure events): Apnea

  during LISA Procedure (T0)

Study Arms (2)

Propofol

EXPERIMENTAL

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)

Drug: Propofol-Lipuro

medialipide

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Propofol-Lipuro DRUG

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

Propofol

Placebos DRUG

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

Also known as: medialipide

medialipide

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (13)

centre hospitalier deTroyes

Troyes, aube, 10000, France

Location

CHU Grenoble Alpes

Grenoble, Isère, 38043, France

Location

Chu Amiens

Amiens, 80000, France

Location

Chu Angers

Angers, 49000, France

Location

Chu Brest

Brest, 29200, France

Location

Chu Chambery

Chambéry, 73000, France

Location

Chi Creteil

Créteil, 94000, France

Location

Chu Limoges

Limoges, 87000, France

Location

Ap-H Marseille

Marseille, 13000, France

Location

Chu Nantes

Nantes, 44000, France

Location

Chu Nimes

Nîmes, 30000, France

Location

Chi Poissy St Germain

Poissy, 78300, France

Location

Ch Rennes

Rennes, 35000, France

Location

Related Publications (13)

• 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.

  PMID: 26907795 BACKGROUND

• 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.

  PMID: 25164872 BACKGROUND

• 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.

  PMID: 21963186 BACKGROUND

• 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.

  PMID: 30068669 BACKGROUND

• 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.

  PMID: 22250028 BACKGROUND

• 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.

  PMID: 29532502 BACKGROUND

• 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.

  PMID: 17485450 BACKGROUND

• 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.

  PMID: 26922562 BACKGROUND

• 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.

  PMID: 23439457 BACKGROUND

• 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.

  PMID: 23359581 BACKGROUND

• 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.

  PMID: 28483817 BACKGROUND

• 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.

  PMID: 27942865 BACKGROUND

• 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.

  PMID: 32384914 DERIVED

MeSH Terms

Conditions

Premature Birth

Interventions

Propofol

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Thierry DEBILLON, MD PHD

  CHU de Grenoble Alpes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: July 11, 2019
• Study Start: October 7, 2019
• Primary Completion: March 18, 2024
• Study Completion (Estimated): October 1, 2026
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (13)