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

August 25, 2021 updated by: University Hospital, Grenoble

Respiratory Effect of the LISA (Less Invasive Surfactant Administration) Method With Sedation by Propofol Versus Absence of Sedation: Double-blind Comparative Randomized Clinical Trial.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

542

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / 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 Names:
  • medialipide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
72hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
72hours
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.
1hour
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.
before LISA Procedure
Number of laryngoscopies
Time Frame: during LISA Procedure (T0)
Number of laryngoscopies needed to perform LISA
during LISA Procedure (T0)
Tolerance and efficacy (Per procedure events): Apnea
Time Frame: during LISA Procedure (T0)
Apnea requiring bag mask ventilation
during LISA Procedure (T0)
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
from drug injection to 1hour after
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.
during LISA Procedure
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
equivalent to 36 weeks of Gestational Age
In-hospital morbidity and mortality: pneumothorax
Time Frame: 72hours post LISA Procedure
Pneumothorax within 72hours
72hours post LISA Procedure
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
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
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
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
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
the day of discharge from hospital (the day depends to each participant : between 36-45weeks of gestational ageGA)
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
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
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
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
Time Frame: equivalent to 36 weeks of Gestational Age
Death at 36 weeks of Gestational Age
equivalent to 36 weeks of Gestational Age
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
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)
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.
2 years (corrected age)
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.
2 years (corrected age)
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.
2 years (corrected age)
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.
2 years (corrected age)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Investigators

  • Principal Investigator: Thierry DEBILLON, MD PHD, CHU de Grenoble Alpes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 7, 2019

Primary Completion (ANTICIPATED)

October 7, 2022

Study Completion (ANTICIPATED)

October 7, 2024

Study Registration Dates

First Submitted

June 7, 2019

First Submitted That Met QC Criteria

July 9, 2019

First Posted (ACTUAL)

July 11, 2019

Study Record Updates

Last Update Posted (ACTUAL)

August 26, 2021

Last Update Submitted That Met QC Criteria

August 25, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC18.123

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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