Clinical Trial Results:
Sedation with sevoflurane versus propofol in patients with Acute Respiratory Distress Syndrome caused by COVID-19 infection
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Summary
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EudraCT number |
2020-001379-34 |
Trial protocol |
ES |
Global end of trial date |
31 Mar 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Nov 2022
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First version publication date |
01 Nov 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SEVO-COVID19
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04359862 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Instituto de Investigación Sanitaria INCLIVA
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Sponsor organisation address |
Avd. Menéndez Pelayo 4, acc, Valencia, Spain, 46010
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Public contact |
Subdirectora Científica, Instituto de Investigación Sanitaria INCLIVA, 0034 961973536, gestioncientifica@incliva.es
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Scientific contact |
Subdirectora Científica, Instituto de Investigación Sanitaria INCLIVA, 0034 961973536, gestioncientifica@incliva.es
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Jul 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the effect of 48-hour treatment with inhaled sevoflurane on arterial oxygenation, assessed by PaO2/FiO2 on day two, in patients with ARDS-CoVid19
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Protection of trial subjects |
The protocol, informed consent form, participant information sheet and any applicable documents were submitted and approved by an appropriate Ethics Committee
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Apr 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 17
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Worldwide total number of subjects |
17
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EEA total number of subjects |
17
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
8
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From 65 to 84 years |
9
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients with Respiratory Distress caused by COVID19 Infection, admitted in the Anaesthesiology department and Intensive Care Unit of the participating hospitals. | |||||||||
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Pre-assignment
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Screening details |
- | |||||||||
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Pre-assignment period milestones
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Number of subjects started |
17 | |||||||||
Number of subjects completed |
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Period 1
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Period 1 title |
Randomization Period (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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SEVOFLURANE Group | |||||||||
Arm description |
25 patients sedated with Sevoflurane via inhalation, starting with 6 ml/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50) | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
SEVOFLURANE
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Medicinal gas, liquefied
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Routes of administration |
Inhalation use
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Dosage and administration details |
starting dose 6 ml/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50)
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Arm title
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PROPOFOL Group | |||||||||
Arm description |
25 patients standard sedation with intravenous propofol, starting with 2 mg/kg/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50) | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
PROPOFOL
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Emulsion for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
starting dose 2 mg/kg/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50)
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Baseline characteristics reporting groups
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Reporting group title |
SEVOFLURANE Group
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Reporting group description |
25 patients sedated with Sevoflurane via inhalation, starting with 6 ml/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
PROPOFOL Group
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Reporting group description |
25 patients standard sedation with intravenous propofol, starting with 2 mg/kg/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
SEVOFLURANE Group
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Reporting group description |
25 patients sedated with Sevoflurane via inhalation, starting with 6 ml/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50) | ||
Reporting group title |
PROPOFOL Group
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Reporting group description |
25 patients standard sedation with intravenous propofol, starting with 2 mg/kg/h and changing every 15 minutes until an adequate level of sedation is achieved ( BIS 40-50) | ||
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End point title |
To evaluate the effect on arterial oxygenation of treatment with inhaled sevoflurane for 48 hours, evaluated by PaO2/FiO2 on the second day, in patients with Acute Respiratory Distress Syndrome caused by COVID-19 infection. | ||||||||||||
End point description |
Difference in PaO2/FiO2 at 48-hour between Sevofluorane and Propofol arms.
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End point type |
Primary
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End point timeframe |
Selection, Visit 1 (24h) and Visit 2 (48h)
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Statistical analysis title |
linear mixed regression model | ||||||||||||
Statistical analysis description |
Continuous variables are expressed as means (±1 SD) or medians (interquartile range [IQR]), and discrete variables as percentages. At baseline, the comparisons of means, medians, and frequencies among treatment groups were carried out using the t-test, Wilcoxon test, and chi-square test, respectively.
A linear mixed regression model (LMRM) was used for the analysis of the primary endpoint. We modeled changes from baseline in PaO2/FiO2 as a longitudinal outcome. Because of hierarchical levels of
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Comparison groups |
SEVOFLURANE Group v PROPOFOL Group
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Number of subjects included in analysis |
17
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Confidence interval |
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End point title |
Assess mortality at 30 days | |||||||||
End point description |
All-cause mortality evaluated at 30 days
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End point type |
Secondary
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End point timeframe |
Administrative censoring was applied at 30-day after randomization. Total follw-up was 30 days.
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| No statistical analyses for this end point | ||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
During the patient's participation in the study
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Adverse event reporting additional description |
No adverse events occurred during the course of the study
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Assessment type |
Systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||
Dictionary version |
4
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| Frequency threshold for reporting non-serious adverse events: 5% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No adverse events occurred during the course of the study |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Apr 2020 |
Protocol modification version 2.0 15 april 2020 |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
