Propofol versus placebo (with rescue with ketamine) before less invasive surfactant administration: study protocol for a multicenter, double-blind, placebo controlled trial (PROLISA).


Journal

BMC pediatrics
ISSN: 1471-2431
Titre abrégé: BMC Pediatr
Pays: England
ID NLM: 100967804

Informations de publication

Date de publication:
08 05 2020
Historique:
received: 14 04 2020
accepted: 29 04 2020
entrez: 10 5 2020
pubmed: 10 5 2020
medline: 15 5 2021
Statut: epublish

Résumé

One major limitation for less invasive surfactant administration (LISA) is the difficulty in providing sedation before this procedure and the competitive risk of respiratory depression versus avoidance of intubation for most sedative or analgesic drugs used in this context. The objective of this study is to compare the need for mechanical ventilation within 72 h of life following premedication with propofol, versus placebo (rescue with ketamine), for the LISA procedure in preterm neonates born before 32 weeks gestational age (wGA). ProLISA is a phase III, non-inferiority, multicenter, double blind, randomized, placebo controlled trial designed according to the SPIRIT Statement. Neonates born before 32 wGA in 12 geographically dispersed Neonatal Intensive Care Units in France needing surfactant will be included from September 2019 to September 2022. A sample of 542 patients is needed. The neonate is randomized to the intervention (propofol) or control placebo group. Open label rescue treatment with ketamine is possible in both groups if FANS (Faceless Acute Neonatal pain Scale) is ≥6. To guide drug administration, FANS is scored before attempting laryngoscopy. Once an adequate score has been obtained, LISA is performed according to a standardized protocol. The primary outcome is the need for mechanical ventilation within 72 h of life. Secondary outcomes are tolerance of the procedure, pain evaluation, hemodynamic and neurologic parameters after the intervention, morbidities before discharge and neurodevelopmental assessment at 2 years of age. This paper describes the first multicenter, double-blind, randomized, placebo-controlled trial on this topic and will provide crucial information to support implementation of the LISA procedure. ClinicalTrials.gov: NCT04016246. Registered 06 June 2019, N°EUDRACT: 2018-002876-41.

Sections du résumé

BACKGROUND
One major limitation for less invasive surfactant administration (LISA) is the difficulty in providing sedation before this procedure and the competitive risk of respiratory depression versus avoidance of intubation for most sedative or analgesic drugs used in this context. The objective of this study is to compare the need for mechanical ventilation within 72 h of life following premedication with propofol, versus placebo (rescue with ketamine), for the LISA procedure in preterm neonates born before 32 weeks gestational age (wGA).
METHODS
ProLISA is a phase III, non-inferiority, multicenter, double blind, randomized, placebo controlled trial designed according to the SPIRIT Statement. Neonates born before 32 wGA in 12 geographically dispersed Neonatal Intensive Care Units in France needing surfactant will be included from September 2019 to September 2022. A sample of 542 patients is needed. The neonate is randomized to the intervention (propofol) or control placebo group. Open label rescue treatment with ketamine is possible in both groups if FANS (Faceless Acute Neonatal pain Scale) is ≥6. To guide drug administration, FANS is scored before attempting laryngoscopy. Once an adequate score has been obtained, LISA is performed according to a standardized protocol. The primary outcome is the need for mechanical ventilation within 72 h of life. Secondary outcomes are tolerance of the procedure, pain evaluation, hemodynamic and neurologic parameters after the intervention, morbidities before discharge and neurodevelopmental assessment at 2 years of age.
DISCUSSION
This paper describes the first multicenter, double-blind, randomized, placebo-controlled trial on this topic and will provide crucial information to support implementation of the LISA procedure.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT04016246. Registered 06 June 2019, N°EUDRACT: 2018-002876-41.

Identifiants

pubmed: 32384914
doi: 10.1186/s12887-020-02112-x
pii: 10.1186/s12887-020-02112-x
pmc: PMC7206779
doi:

Substances chimiques

Pulmonary Surfactants 0
Surface-Active Agents 0
Ketamine 690G0D6V8H
Propofol YI7VU623SF

Banques de données

ClinicalTrials.gov
['NCT04016246']

Types de publication

Clinical Trial Protocol Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

199

Subventions

Organisme : Direction Générale de l'offre de Soins
ID : PHRC-N 170176
Pays : International

Investigateurs

Alain Beuchee (A)
Laura Bourgoin (L)
Aurélie Desenfants (A)
Amélie Durandy (A)
Cyril Flamant (C)
Géraldine Gascoin (G)
Ghida Ghostine (G)
Johanna Parra (J)
Laure Ponthier (L)
Jean-Michel Roué (JM)

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Auteurs

Marie Chevallier (M)

UMR 5525 ThEMAS, CNRS, TIMC-IMAG, Grenoble Alps University, Grenoble, France. mchevallier3@chu-grenoble.fr.
Neonatal Intensive Care Unit, Grenoble Alps University Hospital, Grenoble, France. mchevallier3@chu-grenoble.fr.

Xavier Durrmeyer (X)

Neonatal Intensive Care Unit, Centre Hospitalier Intercommunal de Créteil, Créteil, France.
Université Paris Est, IMRB- GRC GEMINI, Créteil, France.
Inserm, U1153, Obstetrical, Perinatal and Pediatric Epidemiology Team, Epidemiology and Biostatistics Sorbonne, Paris Descartes University, Paris, France.

Anne Ego (A)

Neonatal Intensive Care Unit, Grenoble Alps University Hospital, Grenoble, France.

Thierry Debillon (T)

UMR 5525 ThEMAS, CNRS, TIMC-IMAG, Grenoble Alps University, Grenoble, France.
Neonatal Intensive Care Unit, Grenoble Alps University Hospital, Grenoble, France.

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Classifications MeSH