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

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ClinicalTrials.gov Identifier: NCT04016246
Recruitment Status : Recruiting
First Posted : July 11, 2019
Last Update Posted : October 9, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble

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.

Condition or disease Intervention/treatment Phase
Respiratory Distress Syndrome in Premature Infant Drug: Propofol-Lipuro Drug: Placebos Phase 3

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). 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 542 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : October 7, 2019
Estimated Primary Completion Date : October 7, 2022
Estimated Study Completion Date : October 7, 2024


Arm Intervention/treatment
Experimental: 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)

Drug: Propofol-Lipuro
sedation of babies < 32wGA with propofol / placebo before a LISA Procedure

Placebo Comparator: 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

Drug: Placebos
injected to babies < 32wGA with propofol / placebo before a LISA Procedure
Other Name: medialipide




Primary Outcome Measures :
  1. need for mechanical ventilation after the procedure [ Time Frame: 72hours ]
    Rate of mechanical ventilation from the start of the LISA procedure up to 72 hours of life.


Secondary Outcome Measures :
  1. Rate of MV (mechanical ventilation ) in each class of GA (<28, 28-31wGA) [ Time Frame: 72hours ]

    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)


  2. FANS during LISA and 1h after LISA [ Time Frame: 1hour ]
    Faceless acute neonatal pain scale (FANS) assessed during LISA and 1 hour after the procedure by an independent operator.

  3. number of ketamine administrations for rescue [ Time Frame: before LISA Procedure ]
    Number of ketamine administrations for rescue in order to obtain a FANS score <6 and to be able to proceed to LISA.

  4. Number of laryngoscopies [ Time Frame: during LISA Procedure (T0) ]
    Number of laryngoscopies needed to perform LISA

  5. Tolerance and efficacy (Per procedure events): Apnea [ Time Frame: during LISA Procedure (T0) ]
    Apnea requiring bag mask ventilation

  6. Tolerance and efficacy (Per procedure events): emergency intubation [ Time Frame: from drug injection to 1hour after ]
    Emergency intubation after the drug injection before the LISA procedure can be performed or within 1h following the drug injection

  7. Tolerance and efficacy (Per procedure events): Viby Mogensen score [ Time Frame: during LISA Procedure ]

    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.


  8. BPD (bronchopulmonary dysplasia) at 36 weeks of Gestational Age [ Time Frame: equivalent to 36 weeks of Gestational Age ]
    Broncho Pulmonary Dysplasia at 36 weeks of Gestational Age

  9. In-hospital morbidity and mortality: pneumothorax [ Time Frame: 72hours post LISA Procedure ]
    Pneumothorax within 72hours

  10. In-hospital morbidity and mortality: Necrotizing Enterocolitis [ Time Frame: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age) ]
    necrotizing enterocolitis during hospitalization

  11. In-hospital morbidity and mortality : sepsis [ Time Frame: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age) ]
    proven sepsis during hospitalization

  12. In-hospital morbidity and mortality: retinopathy [ Time Frame: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of gestational ageGA) ]
    retinopathy of prematurity during hospitalization

  13. In-hospital morbidity and mortality [ Time Frame: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of Gestational Age) ]
    periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage during hospitalization

  14. In-hospital morbidity and mortality: patent ductus arteriosus [ Time Frame: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age) ]
    treatment of a patent ductus arteriosus during hospitalization

  15. In-hospital morbidity and mortality: death 36weeks of Gestational Age [ Time Frame: equivalent to 36 weeks of Gestational Age ]
    Death at 36 weeks of Gestational Age

  16. In-hospital morbidity and mortality: death during hospitalization [ Time Frame: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of Gestational Age) ]
    in-hospital mortality

  17. At two years of corrected age: ASQ (Ages and Stages Questionnaire) [ Time Frame: 2 years (corrected age) ]
    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.

  18. At two years of corrected age: motor function [ Time Frame: 2 years (corrected age) ]

    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.


  19. At two years of corrected age: vision [ Time Frame: 2 years (corrected age) ]
    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.

  20. At two years of corrected age: audition [ Time Frame: 2 years (corrected age) ]
    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.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04016246


Contacts
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Contact: Marie CHEVALLIER, MD +33476769248 MChevallier3@chu-grenoble.fr
Contact: cécile LACHAUD +33476765577 clachaud@chu-grenoble.fr

Locations
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France
CHU Grenoble Alpes Recruiting
Grenoble, Isère, France, 38043
Contact: Thierry DEBILLON    +33476765577    tdebillon@chu-grenoble.fr   
Chu Amiens Not yet recruiting
Amiens, France, 80000
Contact: tourneux       Tourneux.Pierre@chu-amiens.fr   
Chu Angers Not yet recruiting
Angers, France, 49000
Contact: gascoin       GeGascoin@chu-angers.fr   
Chu Brest Not yet recruiting
Brest, France, 29200
Contact: roue       jean-michel.roue@chu-brest.fr   
Chu Chambery Not yet recruiting
Chambéry, France, 73000
Contact: parra       johanna.parra@ch-metropole-savoie.fr   
Chi Creteil Not yet recruiting
Créteil, France, 94000
Contact: durrmeyer       Xavier.Durrmeyer@chicreteil.fr   
Chu Limoges Not yet recruiting
Limoges, France, 87000
Contact: ponthier       laure.ponthier@chu-limoges.fr   
Ap-H Marseille Not yet recruiting
Marseille, France, 13000
Contact: bourgouin       laura.bourgouin@ap-hm.fr   
Chu Nantes Not yet recruiting
Nantes, France, 44000
Contact: flamant       cyril.flamant@chu-nantes.fr   
Chu Nimes Not yet recruiting
Nîmes, France, 30000
Contact: desenfants       aurelie.desenfants@chu-nimes.fr   
Chi Poissy St Germain Not yet recruiting
Poissy, France, 78300
Contact: Durandy       adurandy@chi-poissy-st-germain.fr   
Ch Rennes Not yet recruiting
Rennes, France, 35000
Contact: beuchee       alain.beuchee@chu-rennes.fr   
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
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Principal Investigator: Thierry DEBILLON, MD PHD CHU de Grenoble Alpes

Publications of Results:

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Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT04016246     History of Changes
Other Study ID Numbers: 38RC18.123
First Posted: July 11, 2019    Key Record Dates
Last Update Posted: October 9, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Grenoble:
LISA
propofol
medialipide
ketamin
sedation
premature infant
surfactant
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Respiratory Tract Diseases
Infant, Newborn, Diseases
Lung Diseases
Respiration Disorders
Infant, Premature, Diseases
Propofol
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics