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

Grenoble Alpes University Hospital Center (CHU)

Status and phase: Active, not recruiting; Phase 3

Conditions: Respiratory Distress Syndrome in Premature Infant

Treatments: Drug: Propofol-Lipuro; Drug: Placebos

Study type: Interventional

Funder types: Other

Identifiers

NCT04016246

38RC18.123

Details and patient eligibility

About

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.

Full 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.

Enrollment: 233 patients

Sex: All

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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233 participants in 2 patient groups, including a placebo group

Propofol

Experimental group

Description:

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)

Treatment:

Drug: Propofol-Lipuro

medialipide

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebos