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

University Hospital, Grenoble233 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

233

Conditions

Respiratory Distress Syndrome in Premature Infant

Interventions

Propofol-LipuroDRUG

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

PlacebosDRUG

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

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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

Locations (13)

centre hospitalier deTroyes

Troyes, Aube, France

CHU Grenoble Alpes

Grenoble, Isère, France

Chu Amiens

Amiens, France

Chu Angers

Outcomes

Primary Outcomes

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)

Time frame: 72hours

Secondary Outcomes

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)

Time frame: 72hours

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.

Time frame: 1hour

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.

Time frame: before LISA Procedure

Number of laryngoscopies

Number of laryngoscopies needed to perform LISA

Time frame: during LISA Procedure (T0)

Tolerance and efficacy (Per procedure events): Apnea

Apnea requiring bag mask ventilation

Time frame: during LISA Procedure (T0)

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

Data from ClinicalTrials.gov

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Chu Brest

Brest, France

Chu Chambery

Chambéry, France

Chi Creteil

Créteil, France

Chu Limoges

Limoges, France

Ap-H Marseille

Marseille, France

Chu Nantes

Nantes, France

...and 3 more locations

Time frame: from drug injection to 1hour after

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.

Time frame: during LISA Procedure

BPD (bronchopulmonary dysplasia) at 36 weeks of Gestational Age

Broncho Pulmonary Dysplasia at 36 weeks of Gestational Age

Time frame: equivalent to 36 weeks of Gestational Age

In-hospital morbidity and mortality: pneumothorax

Pneumothorax within 72hours

Time frame: 72hours post LISA Procedure

In-hospital morbidity and mortality: Necrotizing Enterocolitis

necrotizing enterocolitis during hospitalization

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

In-hospital morbidity and mortality : sepsis

proven sepsis during hospitalization

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

In-hospital morbidity and mortality: retinopathy

retinopathy of prematurity during hospitalization

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

In-hospital morbidity and mortality

periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage during hospitalization

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

In-hospital morbidity and mortality: patent ductus arteriosus

treatment of a patent ductus arteriosus during hospitalization

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

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

Death at 36 weeks of Gestational Age

Time frame: equivalent to 36 weeks of Gestational Age

In-hospital morbidity and mortality: death during hospitalization

in-hospital mortality

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

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.

Time frame: 2 years (corrected age)

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.

Time frame: 2 years (corrected age)

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.

Time frame: 2 years (corrected age)

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.

Time frame: 2 years (corrected age)