Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43874   clinical trials with a EudraCT protocol, of which   7294   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Methoxyflurane and fentanyl in hypovolemia induced by lower body negative pressure in healthy volunteers; A randomized, placebo-controlled crossover study

    Summary
    EudraCT number
    		 2019-004144-29
    Trial protocol
    		 NO  
    Global end of trial date
    05 Jan 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Jul 2023
    First version publication date
    01 Jul 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    lbnp_methoxy_fent_2019
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04641949
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Oslo University Hospital
    Sponsor organisation address
    Kirkeveien 166, Oslo, Norway, 0450
    Public contact
    Department of Anesthesiology, Oslo University Hospital, 47 22119690, lars.oivind.hoiseth@hotmail.com
    Scientific contact
    Department of Anesthesiology, Oslo University Hospital, 90749409 +4722119690, lars.oivind.hoiseth@hotmail.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 Jan 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    05 Jan 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Jan 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The objective of the trial is to study if and how the hemodynamic effects of experimental hypovolemia are affected by methoxyflurane and fentanyl compared to placebo. The primary outcome is cardiac stroke volume, and the main secondary outcome is time to time to termination of hypovolemic exposure.
    Protection of trial subjects
    The trial was carried out in accordance with the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Feb 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Norway: 15
    Worldwide total number of subjects
    15
    EEA total number of subjects
    15
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    15
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Fifteen helathy volunteers were included in this single-centre study performed at Oslo Univeristy Hospital, Aker. First visit of first subject was December 2020, and last visit of last subject was March 2022.

    Pre-assignment
    Screening details
    		 Fifteen subjects were screened for participation, and all screened subjects entered and completed all visits.

    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Data analyst
    Blinding implementation details
    The trial was blinded with a crossover design. Three treatments were administered; methoxyflurane, fentanyl or 0.9% saline (placebo). Subjects, investigators present during the visits were blinded. And analysis of primary outcome was performed before unblinding.

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Methoxyflurane
    Arm description
    		 Inhalation Methoxyflurane 3 ml.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Methoxyflurane
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    3 ml methoxyflurane 99.9% inhaled withous occluding the dilotor hole.

    Arm title
    		 Fentanyl
    Arm description
    		 Fentanyl 15µg intravenously.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fentanyl
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    Fentanyl 50µg/ml * 0.5 ml = 25µg injection.

    Arm title
    		 Placebo
    Arm description
    		 Saline (0.9%) intravenously and in inhalator.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Saline
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Gastric use, Intravenous bolus use
    Dosage and administration details
    3 ml. saline in inhaler and 0.5 ml saline for intravenous injection.

    Number of subjects in period 1
    		Methoxyflurane Fentanyl Placebo
    Started
    15
    15
    15
    Completed
    15
    15
    15
    Period 2
    Period 2 title
    Visits 1, 2 and 3.
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Data analyst
    Blinding implementation details
    Inhaler was filled with methoxyflurane or saline. Fentanyl og saline was given intravenously.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Methoxyflurane
    Arm description
    		 Inhalation Methoxyflurane 3 ml.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Methoxyflurane
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Inhalation solution
    Routes of administration
    Inhalation use
    Dosage and administration details
    3 ml methoxyflurane 99.9% inhaled withous occluding the dilotor hole.

    Arm title
    		 Fentanyl
    Arm description
    		 Fentanyl 15µg intravenously.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Fentanyl
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous bolus use
    Dosage and administration details
    Fentanyl 50µg/ml * 0.5 ml = 25µg injection.

    Arm title
    		 Placebo
    Arm description
    		 Saline (0.9%) intravenously and in inhalator.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Saline
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Gastric use, Intravenous bolus use
    Dosage and administration details
    3 ml. saline in inhaler and 0.5 ml saline for intravenous injection.

    Number of subjects in period 2
    		Methoxyflurane Fentanyl Placebo
    Started
    15
    15
    15
    Completed
    15
    15
    15

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Baseline
    Reporting group description
    		 -

    Reporting group values
    		 Baseline Total
    Number of subjects
    		 15 15
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 15 15
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
        All subjects
    		 0 0
    Gender categorical
    Units: Subjects
        Female
    		 7 7
        Male
    		 8 8
    Subject analysis sets

    Subject analysis set title
    Methoxyflurane
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Effect of methoxyflurane compared to placebo.

    Subject analysis sets values
    		 Methoxyflurane
    Number of subjects
    15
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    15
        From 65-84 years
    0
        85 years and over
    0
        All subjects
    15
    Age continuous
    Units:
        
    ( )
    Gender categorical
    Units: Subjects
        Female
    7
        Male
    8

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Methoxyflurane
    Reporting group description
    		 Inhalation Methoxyflurane 3 ml.

    Reporting group title
    Fentanyl
    Reporting group description
    		 Fentanyl 15µg intravenously.

    Reporting group title
    Placebo
    Reporting group description
    		 Saline (0.9%) intravenously and in inhalator.
    Reporting group title
    Methoxyflurane
    Reporting group description
    		 Inhalation Methoxyflurane 3 ml.

    Reporting group title
    Fentanyl
    Reporting group description
    		 Fentanyl 15µg intravenously.

    Reporting group title
    Placebo
    Reporting group description
    		 Saline (0.9%) intravenously and in inhalator.

    Subject analysis set title
    Methoxyflurane
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Effect of methoxyflurane compared to placebo.

    Primary: Cardiac output

    		 Close Top of page
    End point title
    		 Cardiac output
    End point description
    Effect of treatment on cardiac output during lower body negative pressure.
    End point type
    Primary
    End point timeframe
    During experimental intervention, approximately 30 min.
    End point values
    		 Methoxyflurane Fentanyl Placebo
    Number of subjects analysed
    15
    15
    15
    Units: litres per minute
        number (not applicable)
    15
    15
    15
    Statistical analysis title
    		 Effect of methoxyflurane
    Statistical analysis description
    Effect of methoxyflurane on the effect of LBNP on cardiac output (interaction effect).
    Comparison groups
    Methoxyflurane v Placebo
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.625 [1]
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.012
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.06
         upper limit
    		 0.036
    Notes
    [1] - P-value for interaction effect of methoxyflurane compared to placebo.
    Statistical analysis title
    		 Effect of fentanyl
    Statistical analysis description
    Effect of fentanyl on the effect of LBNP on cardiac output (interaction effect).
    Comparison groups
    Placebo v Fentanyl
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.134 [2]
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.039
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.012
         upper limit
    		 0.134
    Notes
    [2] - P-value for interaction effect of fentanyl compared to placebo.

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    To end of last visit (one month after last IMP).
    Adverse event reporting additional description
    There were no adverse events reported.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    All subjects
    Reporting group description
    		 All subjects received methoxyflurane 3 ml, fentanyl 25µg and placebo with a crossover design. All subjects received all treatments/ IMPs.

    Serious adverse events
    		 All subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 15 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 All subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 15 (0.00%)
    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: There were no adverse events recorded during this trial.

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 17 04:36:57 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA