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

Respiratory Distress Syndrome in Premature Infant Clinical Trial

— PROLISA  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04016246
• Other study ID #: 38RC18.123
• Status: Recruiting
• Phase: Phase 3
• Start date: October 7, 2019
• Est. completion date: October 7, 2024

Study information

• Verified date: April 2021
• Source: University Hospital, Grenoble
• Contact: Marie CHEVALLIER, MD
• Phone: +33476769248
• Email: MChevallier3[@]chu-grenoble.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 542
• Est. completion date: October 7, 2024
• Est. primary completion date: October 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Respiratory Distress Syndrome in Premature Infant
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

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

Locations

Country	Name	City	State
France	Chu Amiens	Amiens
France	Chu Angers	Angers
France	Chu Brest	Brest
France	Chu Chambery	Chambéry
France	Chi Creteil	Créteil
France	CHU Grenoble Alpes	Grenoble	Isère
France	Chu Limoges	Limoges
France	Ap-H Marseille	Marseille
France	Chu Nantes	Nantes
France	Chu Nimes	Nîmes
France	Chi Poissy St Germain	Poissy
France	Ch Rennes	Rennes
France	centre hospitalier deTroyes	Troyes	Aube

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Grenoble

Country where clinical trial is conducted

France, 

References & Publications (12)

Berde CB, Walco GA, Krane EJ, Anand KJ, Aranda JV, Craig KD, Dampier CD, Finkel JC, Grabois M, Johnston C, Lantos J, Lebel A, Maxwell LG, McGrath P, Oberlander TF, Schanberg LE, Stevens B, Taddio A, von Baeyer CL, Yaster M, Zempsky WT. Pediatric analgesic — View Citation

Bourgoin L, Caeymaex L, Decobert F, Jung C, Danan C, Durrmeyer X. Administering atropine and ketamine before less invasive surfactant administration resulted in low pain scores in a prospective study of premature neonates. Acta Paediatr. 2018 Jul;107(7):1 — View Citation

Dargaville PA, Kamlin CO, De Paoli AG, Carlin JB, Orsini F, Soll RF, Davis PG. The OPTIMIST-A trial: evaluation of minimally-invasive surfactant therapy in preterm infants 25-28 weeks gestation. BMC Pediatr. 2014 Aug 27;14:213. doi: 10.1186/1471-2431-14-2 — View Citation

Dekker J, Lopriore E, Rijken M, Rijntjes-Jacobs E, Smits-Wintjens V, Te Pas A. Sedation during Minimal Invasive Surfactant Therapy in Preterm Infants. Neonatology. 2016;109(4):308-13. doi: 10.1159/000443823. Epub 2016 Feb 24. — View Citation

Dekker J, Lopriore E, van Zanten HA, Tan RNGB, Hooper SB, Te Pas AB. Sedation during minimal invasive surfactant therapy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019 Jul;104(4):F378-F383. doi: 10.1136/archdischild-2018-315015. Ep — View Citation

Descamps CS, Chevallier M, Ego A, Pin I, Epiard C, Debillon T. Propofol for sedation during less invasive surfactant administration in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2017 Sep;102(5):F465. doi: 10.1136/archdischild-2017-312791. Epub 201 — View Citation

Durrmeyer X, Daoud P, Decobert F, Boileau P, Renolleau S, Zana-Taieb E, Saizou C, Lapillonne A, Granier M, Durand P, Lenclen R, Coursol A, Nicloux M, de Saint Blanquat L, Shankland R, Boëlle PY, Carbajal R. Premedication for neonatal endotracheal intubati — View Citation

Ghanta S, Abdel-Latif ME, Lui K, Ravindranathan H, Awad J, Oei J. Propofol compared with the morphine, atropine, and suxamethonium regimen as induction agents for neonatal endotracheal intubation: a randomized, controlled trial. Pediatrics. 2007 Jun;119(6 — View Citation

Göpel W, Kribs A, Ziegler A, Laux R, Hoehn T, Wieg C, Siegel J, Avenarius S, von der Wense A, Vochem M, Groneck P, Weller U, Möller J, Härtel C, Haller S, Roth B, Herting E; German Neonatal Network. Avoidance of mechanical ventilation by surfactant treatm — View Citation

Kanmaz HG, Erdeve O, Canpolat FE, Mutlu B, Dilmen U. Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial. Pediatrics. 2013 Feb;131(2):e502-9. doi: 10.1542/peds.2012-0603. Epub 2013 Jan 28. — View Citation

Klotz D, Porcaro U, Fleck T, Fuchs H. European perspective on less invasive surfactant administration-a survey. Eur J Pediatr. 2017 Feb;176(2):147-154. doi: 10.1007/s00431-016-2812-9. Epub 2016 Dec 9. — View Citation

Owen LS, Manley BJ. Nasal intermittent positive pressure ventilation in preterm infants: Equipment, evidence, and synchronization. Semin Fetal Neonatal Med. 2016 Jun;21(3):146-53. doi: 10.1016/j.siny.2016.01.003. Epub 2016 Feb 26. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	need for mechanical ventilation after the procedure	Rate of mechanical ventilation from the start of the LISA procedure up to 72 hours of life.	72hours
Secondary	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)	72hours
Secondary	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.	1hour
Secondary	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.	before LISA Procedure
Secondary	Number of laryngoscopies	Number of laryngoscopies needed to perform LISA	during LISA Procedure (T0)
Secondary	Tolerance and efficacy (Per procedure events): Apnea	Apnea requiring bag mask ventilation	during LISA Procedure (T0)
Secondary	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	from drug injection to 1hour after
Secondary	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.	during LISA Procedure
Secondary	BPD (bronchopulmonary dysplasia) at 36 weeks of Gestational Age	Broncho Pulmonary Dysplasia at 36 weeks of Gestational Age	equivalent to 36 weeks of Gestational Age
Secondary	In-hospital morbidity and mortality: pneumothorax	Pneumothorax within 72hours	72hours post LISA Procedure
Secondary	In-hospital morbidity and mortality: Necrotizing Enterocolitis	necrotizing enterocolitis during hospitalization	the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age)
Secondary	In-hospital morbidity and mortality : sepsis	proven sepsis during hospitalization	the day of discharge from hospital (the day depends to each participant : between 36-45 weeks of Gestational Age)
Secondary	In-hospital morbidity and mortality: retinopathy	retinopathy of prematurity during hospitalization	the day of discharge from hospital (the day depends to each participant : between 36-45weeks of gestational ageGA)
Secondary	In-hospital morbidity and mortality	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)
Secondary	In-hospital morbidity and mortality: patent ductus arteriosus	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)
Secondary	In-hospital morbidity and mortality: death 36weeks of Gestational Age	Death at 36 weeks of Gestational Age	equivalent to 36 weeks of Gestational Age
Secondary	In-hospital morbidity and mortality: death during hospitalization	in-hospital mortality	the day of discharge from hospital (the day depends to each participant : between 36-45weeks of Gestational Age)
Secondary	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.	2 years (corrected age)
Secondary	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.	2 years (corrected age)
Secondary	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.	2 years (corrected age)
Secondary	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.	2 years (corrected age)