Randomized Clinical Trial of Inhaled Sedation with Sevoflurane in Critically Ill Patients at Risk of Developing the Acute Respiratory Distress Syndrome

2024-517670-15-00 Protocol AOI 2019 JABAUDON Therapeutic confirmatory (Phase III) Ended

Start 24 Jul 2023 · End 13 Apr 2026 · Status Ended · 1 EU/EEA countries · 1 sites · Protocol AOI 2019 JABAUDON

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 80
Countries 1
Sites 1

Patients in ICU with risks of Acute Respiratory Distress Syndrome

To assess the efficacy of inhaled sevoflurane, compared to current intravenous sedation practice, for improving PaO2/FiO2 in ICU patients at high risk for ARDS.

Key facts

Sponsor
CHU Gabriel-Montpied
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]
Trial duration
24 Jul 2023 → 13 Apr 2026
Decision date (initial)
2024-10-10
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
CHU de Clermont-Ferrand

External identifiers

EU CT number
2024-517670-15-00
EudraCT number
2020-001813-18
ClinicalTrials.gov
NCT05849779

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To assess the efficacy of inhaled sevoflurane, compared to current intravenous sedation practice, for improving PaO2/FiO2 in ICU patients at high risk for ARDS.

Secondary objectives 13

  1. Progression to ARDS, as defined by the Berlin criteria
  2. Safety (clinical adverse events) of the two sedation strategies
  3. Effects on the rate of pneumonia
  4. Effects on respiratory mechanics
  5. Effects on gas exchange and physiologic measures
  6. Effects on ICU-acquired delirium
  7. Effects on hemodynamic measures and renal function (KDIGO criteria for acute kidney injury)
  8. Effects on organ dysfunction
  9. Effects on the duration of mechanical ventilation
  10. Effects on 28-day mortality
  11. Effects on the number of days off the ventilator at 28 days, taking into account death as a competing event
  12. Biological collection of plasma samples for future mechanistic and endotyping studies of the biological effects of sevoflurane
  13. Presence of subphenotypes among patients at risk of developing ARDS

Conditions and MedDRA coding

Patients in ICU with risks of Acute Respiratory Distress Syndrome

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Sedation
patients will receive the allocated sedation strategy from randomization until sedation can be definitely interrupted or until day 5, whichever occurs first
 Randomised Controlled None Inhaled sedation with sevoflurane: treatment for sedation is sevoflurane
Intravenous sedation: We will not mandate the sedative type, but rather encourage the use of sedatives that are already routinely used in participating ICUs (typically a benzodiazepine propofol, or dexmedetomidine, i.e. drugs approved for sedation)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

  1. Age ≥ 18 years
  2. Admitted to participating ICUs with at least one known risk factor for ARDS and a LIPS equals to, or greater than 4
  3. Patient under invasive mechanical ventilation
  4. With expected duration of sedation superior or equal to 4 hours
  5. Affiliation to the French Sécurité Sociale

Exclusion criteria 16

  1. Patient under a tutelage measure
  2. Medical history of malignant hyperthermia
  3. Long QT syndrome at risk of arrhythmic events
  4. Medical history of liver disease attributed to previous exposure to a halogenated agent (including sevoflurane)
  5. Suspected or proven intracranial hypertension
  6. Enrollment in another interventional trial with direct impact on oxygenation
  7. Patient under judicial protection, guardianship or supervision
  8. Patient under psychiatric care as defined by art. L1121-6 of the Public Health Code
  9. Known pregnancy
  10. Presence of ARDS prior to randomization
  11. Endotracheal ventilation for greater than 24 hours prior to randomization
  12. Home mechanical ventilation (non-invasive ventilation or via tracheotomy) except for CPAP/BIPAP used solely for sleep-disordered breathing
  13. Tidal volume of 6 mL/kg predicted body weight (PBW) below 200 mL (i.e. height inferior to 134cm for a man and 139cm for a woman)
  14. Moribund patient, i.e. not expected to survive 24 hours despite intensive care
  15. Previous hypersensitivity or anaphylactic reaction to sevoflurane or to the intravenous sedation agent routinely used in the participating ICU (such as midazolam, propofol, or dexmedetomidine)
  16. Contra-indications to the intravenous sedative agent routinely used in the participating ICU (such as midazolam, propofol, or dexmedetomidine

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. longitudinal evolution in the PaO2/FiO2 ratio

Secondary endpoints 9

  1. Progression to ARDS will be assessed according to the Berlin criteria, including chest radiographs
  2. Rate of pneumonia
  3. Ventilator-free days
  4. Organ failure-free days
  5. Mortality
  6. Length of ICU-stay
  7. Physiological measures
  8. ICU-acquired delirium
  9. Biomarker measurements

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

SEVOFLURANE BAXTER 1 ml/ml, liquide pour inhalation par vapeur

PRD316592 · Product

Active substance
Sevoflurane
Pharmaceutical form
INHALATION VAPOUR, LIQUID
Route of administration
INHALATION USE
Max daily dose
250 ml millilitre(s)
Max total dose
1250 ml millilitre(s)
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
N01AB08 — SEVOFLURANE
Marketing authorisation
34009 567 478 9 4
MA holder
BAXTER SAS
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Comparator 3

HYPNOVEL 1 mg/ml, solution injectable

PRD7669840 · Product

Active substance
Midazolam
Substance synonyms
USL-261
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
5 mg milligram(s)
Max total dose
25 mg milligram(s)
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
N05CD08 — MIDAZOLAM
Marketing authorisation
34009 557 550 9 8
MA holder
CHEPLAPHARM ARZNEIMITTEL GMBH
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Dexmedetomidine 100 micrograms/ml concentrate for solution for infusion

PRD10126121 · Product

Active substance
Dexmedetomidine
Pharmaceutical form
SOLUTION FOR INFUSION
Route of administration
INTRAVENOUS
Max daily dose
24 µg/Kg microgram(s)/kilogram
Max total dose
120 µg/Kg microgram(s)/kilogram
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
N05CM18 — -
Marketing authorisation
PL 03551/0161
MA holder
B.BRAUN MELSUNGEN AG
MA country
XI
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

DIPRIVAN 20 mg/ml, émulsion injectable en seringue pré-remplie

PRD4875492 · Product

Active substance
Propofol
Substance synonyms
2,6-Bis(PROPAN-2-YL)PHENOL, ICI-35868, DISOPROFOL
Pharmaceutical form
EMULSION FOR INJECTION
Route of administration
INTRAVENOUS USE
Max daily dose
1.5 mg/Kg milligram(s)/kilogram
Max total dose
7.5 mg/Kg milligram(s)/kilogram
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
N01AX10 — PROPOFOL
Marketing authorisation
34009 563 611 6 8
MA holder
ASPEN PHARMA TRADING LIMITED
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Auxiliary 1

NIMBEX 5 mg/ml, solution injectable/pour perfusion

PRD5214865 · Product

Active substance
Cisatracurium Besilate
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
12960 µg/Kg microgram(s)/kilogram
Max total dose
25920 µg/Kg microgram(s)/kilogram
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
M03AC11 — CISATRACURIUM
Marketing authorisation
34009 559 539 2 0
MA holder
ASPEN PHARMA TRADING LIMITED
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHU Gabriel-Montpied

4 Total trials 2 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
CHU Gabriel-Montpied
Address
58 Rue Montalembert
City
Clermont Ferrand
Postcode
63000
Country
France

Scientific contact point

Organisation
CHU Gabriel-Montpied
Contact name
Lise Laclautre

Public contact point

Organisation
CHU Gabriel-Montpied
Contact name
Lise Laclautre

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ended 80 1
Rest of world — 0 —

Investigational sites

France

1 site · Ended
University Hospital Of Clermont-Ferrand
Anesthésie-réanimation, 1 Place Lucie Et Raymond Aubrac, 63100, Clermont-Ferrand

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2023-07-24 2023-07-24 2026-04-13

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol_2024-517670-15-00 7
Protocol (for publication) D1_Protocol_2024-517670-15-00_TC 7
Protocol (for publication) D1_Signature-protocol_2024-517670-15-00 7
Protocol (for publication) D1_tableau-comparatif-protocole_2024-517670-15-00 1
Recruitment arrangements (for publication) Blank document 1
Subject information and informed consent form (for publication) 2020-001813-18_INF-Patient-Poursuite_20221220_IPA Study V4 4
Subject information and informed consent form (for publication) 2020-001813-18_INF-Proche_20221220_IPA Study V4 4
Summary of Product Characteristics (SmPC) (for publication) G1_Comparateur_DEXMEDETOMIDINE 1
Summary of Product Characteristics (SmPC) (for publication) G1_Comparateur_Diprivan 1
Summary of Product Characteristics (SmPC) (for publication) G1_Comparateur_Hypnovel 1
Summary of Product Characteristics (SmPC) (for publication) H1_DM Anaconda 1
Summary of Product Characteristics (SmPC) (for publication) RCP_Sevoflurane 1
Synopsis of the protocol (for publication) 2020-001813-18_Resume_V6_20240426_IPA Study 6

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-17 France Acceptable
2024-10-10
 2024-10-10
2 NON SUBSTANTIAL MODIFICATION NSM-1 2025-11-10 France Acceptable
2024-10-10
 2025-11-10

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