Clinical trial NCT04016246: Respiratory Effect of the LISA Method with Sedation by Propofol Versus Absence of Sedation.
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Respiratory Distress Syndrome in Premature Infant
Keywords: LISA
propofol
medialipide
ketamin
sedation
premature infant
surfactant
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2019-07-11
Enrollment: 233
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: need for mechanical ventilation after the procedure
timeFrame: 72hours
Secondary outcomes:
measure: Rate of MV (mechanical ventilation ) in each class of GA (<28, 28-31wGA)
timeFrame: 72hours
measure: FANS during LISA and 1h after LISA
timeFrame: 1hour
measure: number of ketamine administrations for rescue
timeFrame: before LISA Procedure
measure: Number of laryngoscopies
timeFrame: during LISA Procedure (T0)
measure: Tolerance and efficacy (Per procedure events): Apnea
timeFrame: during LISA Procedure (T0)
measure: Tolerance and efficacy (Per procedure events): emergency intubation
timeFrame: from drug injection to 1hour after
measure: Tolerance and efficacy (Per procedure events): Viby Mogensen score
timeFrame: during LISA Procedure
measure: BPD (bronchopulmonary dysplasia) at 36 weeks of Gestational Age
timeFrame: equivalent to 36 weeks of Gestational Age
measure: In-hospital morbidity and mortality: pneumothorax
timeFrame: 72hours post LISA Procedure
measure: In-hospital morbidity and mortality: Necrotizing Enterocolitis
timeFrame: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age)
measure: In-hospital morbidity and mortality : sepsis
timeFrame: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age)
measure: In-hospital morbidity and mortality: retinopathy
timeFrame: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of gestational ageGA)
measure: In-hospital morbidity and mortality
timeFrame: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of Gestational Age)
measure: In-hospital morbidity and mortality: patent ductus arteriosus
timeFrame: the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age)
measure: In-hospital morbidity and mortality: death 36weeks of Gestational Age
timeFrame: equivalent to 36 weeks of Gestational Age
measure: In-hospital morbidity and mortality: death during hospitalization
timeFrame: the day of discharge from hospital (the day depends to each participant : between 36-45weeks of Gestational Age)
measure: At two years of corrected age: ASQ (Ages and Stages Questionnaire)
timeFrame: 2 years (corrected age)
measure: At two years of corrected age: motor function
timeFrame: 2 years (corrected age)
measure: At two years of corrected age: vision
timeFrame: 2 years (corrected age)
measure: At two years of corrected age: audition
timeFrame: 2 years (corrected age)
Other outcomes:
Locations:
city: Troyes
country: France
facility: centre hospitalier deTroyes
state: Aube
city: Grenoble
country: France
facility: CHU Grenoble Alpes
state: Isère
city: Amiens
country: France
facility: Chu Amiens
city: Angers
country: France
facility: Chu Angers
city: Brest
country: France
facility: Chu Brest
city: Chambéry
country: France
facility: Chu Chambery
city: Créteil
country: France
facility: Chi Creteil
city: Limoges
country: France
facility: Chu Limoges
city: Marseille
country: France
facility: Ap-H Marseille
city: Nantes
country: France
facility: Chu Nantes
city: Nîmes
country: France
facility: Chu Nimes
city: Poissy
country: France
facility: Chi Poissy St Germain
city: Rennes
country: France
facility: Ch Rennes
Study officials:
affiliation: CHU de Grenoble Alpes
name: Thierry DEBILLON, MD PHD
role: PRINCIPAL_INVESTIGATOR
References:
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