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    Clinical Trial Results:
    Therapeutic Equivalence Study of Propofol Using Target-Controlled Infusion of Propofol 2% (20 mg/mL) MCT Fresenius Compared with Diprivan 20 mg/mL (AstraZeneca) in Patients Undergoing Elective Surgery

    Summary
    EudraCT number
    2012-005701-43
    Trial protocol
    FR  
    Global end of trial date
    13 Feb 2014

    Results information
    Results version number
    v1(current)
    This version publication date
    08 Apr 2016
    First version publication date
    01 Aug 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    PROP-001-CP3
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01856998
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Fresenius Kabi Deutschland GmbH
    Sponsor organisation address
    Else-Kröner-Str. 1, Bad Homburg, Germany, 61352
    Public contact
    Division Medical & Clinical Affairs Generics & Standard Solutions, Volume Therapy, Fresenius Kabi Deutschland GmbH, scientific-contact@fresenius-kabi.com
    Scientific contact
    Division Medical & Clinical Affairs Generics & Standard Solutions, Volume Therapy, Fresenius Kabi Deutschland GmbH, scientific-contact@fresenius-kabi.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
    26 Mar 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    31 Jan 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Feb 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the therapeutic equivalence, based on pharmacodynamic parameters, of Propofol 2% (20 mg/mL) MCT Fresenius and Diprivan 20 mg/mL (AstraZeneca) administered by target-controlled infusion (TCI)
    Protection of trial subjects
    It was the responsibility of the Investigator to obtain a signed informed consent form from all patients prior to inclusion in the study. After administration of propofol, the patient was observed for an appropriate period of time. Circulatory and respiratory functions were constantly monitored (e.g. electrocardiogram [ECG], pulse oximetry) and facilities for maintenance of patient airways, artificial ventilation, and other resuscitation facilities were immediately available at all times. For sedation during surgical and diagnostic procedures, propofol was not administered by the same person conducting the surgical or diagnostic procedure. Infusion of colloids was to replace estimated blood loss in a 1:1 ratio with continuous infusion of iso-oncotic colloid. The type of colloid product used was selected as per standard of care. Suspected hypovolaemia could have been treated with boluses of colloid solution in increments of 100 to 250 mL. If hypovolaemia was not a threat to the welfare of the patient, colloid administration was to be kept to ≤500 mL. Prior to emergence from anaesthesia the patient could have been administered medication for post operative nausea and vomiting as per local standard of care. The patient was monitored and received post-anaesthesia care as per local standard of care. Patients were determined eligible for discharge from the peri-procedural setting as per local standard of care, but were not allowed to go home unaccompanied. If discharged home, the patient was instructed not to consume alcohol, to drive, to operate machinery, or to work in potentially hazardous situations for a suitable period following recovery from anaesthesia as per local standard of care.
    Background therapy
    -
    Evidence for comparator
    Propofol was first developed and patented by ICI (now AstraZeneca), marketed under the proprietary name Diprivan
    Actual start date of recruitment
    28 May 2013
    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
    France: 71
    Worldwide total number of subjects
    71
    EEA total number of subjects
    71
    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)
    70
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The trial was monocentric and conducted in France. 1st patient was enrolled on 28 May 2013 and last patient completed the study on 13 Feb 2014. A total of 71 patients were enrolled of whom 70 were randomised: 35 to Propofol MCT Fresenius and 35 to Diprivan. All randomised patients received treatment as per the protocol and all completed the study.

    Pre-assignment
    Screening details
    Included were male and female patients, ≥18 to <65 years of age, with ASA physical status 1 or 2 and undergoing elective, minor orthopaedic, vascular, urological, and gynaecological surgery. One patient was enrolled but not randomised to treatment; patient was deemed a screening failure due to violation of an exclusion criterion.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer
    Blinding implementation details
    All study procedures in the surgery room were performed by a blinded anaesthetist and a blinded nurse. Randomisation and blinding procedures (preparation of syringes) were performed by another unblinded nurse, in another room. The empty used study drug vials were packed and carried back to the pharmacy for storage before the unblinded monitoring visit, performed by an unblinded monitor.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Propofol 2% (20 mg/mL) MCT Fresenius
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Propofol 2% (20 mg/mL) MCT Fresenius
    Investigational medicinal product code
    Other name
    Propofol 20 mg/ml
    Pharmaceutical forms
    Emulsion for injection/infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosage: Initial effect-site target concentration: 5 μg/mL, if necessary increased by 1 μg/mL every 60 seconds until Loss of Eyelash Reflex (LOER). Frequency: Continuously (was adjusted to keep Bispectral Index (BIS) between 40 and 60, however maintenance target concentration could have been increased if a patient needs a BIS <40 with regard to individual condition and the respective surgery). Duration: Until end of surgery

    Arm title
    Diprivan 20 mg/mL (AstraZeneca)
    Arm description
    -
    Arm type
    Active comparator

    Investigational medicinal product name
    Diprivan 20 mg/mL (AstraZeneca)
    Investigational medicinal product code
    Other name
    Propofol 20 mg/ml
    Pharmaceutical forms
    Emulsion for injection/infusion in pre-filled syringe
    Routes of administration
    Intravenous use
    Dosage and administration details
    Dosage: Initial effect-site target concentration: 5 µg/mL; if necessary increased by 1 μg/mL every 60 seconds until Loss of Eyelash Reflex (LOER). Frequency: Continuously (was adjusted to keep Bispectral Index (BIS) between 40 and 60, however maintenance target concentration could have been increased if a patient needed a BIS <40 with regard to individual condition and the respective surgery). Duration: Until end of surgery

    Number of subjects in period 1 [1]
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Started
    35
    35
    Completed
    35
    35
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: In this study 'enrolled patients' defines all patients who had provided informed consent for this study (N=71). One of the 71 enrolled patients was not randomised to treatment and thus has not entered the baseline period. Therefore only 70 patients entered the baseline period.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Propofol 2% (20 mg/mL) MCT Fresenius
    Reporting group description
    -

    Reporting group title
    Diprivan 20 mg/mL (AstraZeneca)
    Reporting group description
    -

    Reporting group values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca) Total
    Number of subjects
    35 35 70
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    35 34 69
        From 65-84 years
    0 1 1
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    44.6 ± 10.54 48 ± 9.39 -
    Gender categorical
    Units: Subjects
        Female
    12 17 29
        Male
    23 18 41

    End points

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    End points reporting groups
    Reporting group title
    Propofol 2% (20 mg/mL) MCT Fresenius
    Reporting group description
    -

    Reporting group title
    Diprivan 20 mg/mL (AstraZeneca)
    Reporting group description
    -

    Primary: Time to Loss of Eyelash Reflex (LOER)

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    End point title
    Time to Loss of Eyelash Reflex (LOER)
    End point description
    The study drug infusion was administered beginning at an initial effect-site target propofol concentration of 5 μg/mL. LOER was to be assessed by gently touching the patient’s eyelashes. If LOER had not occurred within 150 seconds of starting study drug infusion, target propofol effect-site concentration was to be increased by 1 μg/mL every 60 seconds until LOER was observed.
    End point type
    Primary
    End point timeframe
    LOER was to be assessed every 10 seconds from the initiation of TCI anaesthesia (device mediated study drug infusion) until LOER occurred up to 150 seconds. The overall timeframe until LOER is observed varies from patient to patient.
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    34 [1]
    35 [2]
    Units: Minutes
        arithmetic mean (standard deviation)
    2.602 ± 1.49412
    2.5096 ± 1.40146
    Notes
    [1] - Intention-to-treat (ITT) analysis set
    [2] - Intention-to-treat (ITT) analysis set
    Statistical analysis title
    Therapeutic Equivalence
    Statistical analysis description
    No formal statistical inference was required by the ANSM (French Health Authority). But a descriptive comparison of the primary endpoint (time to LOER) between the test and reference treatment was performed using analysis of variance (ANOVA) with a single fixed effect for treatment. This analysis was specified as descriptive since the study was not powered for the comparison. Treatment difference (test – reference) with 90% confidence intervals (CI) are presented for the ITT population.
    Comparison groups
    Propofol 2% (20 mg/mL) MCT Fresenius v Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    equivalence
    Method
    Parameter type
    Mean difference (final values)
    Point estimate
    0.092
    Confidence interval
         level
    90%
         sides
    2-sided
         lower limit
    -0.489
         upper limit
    0.674

    Secondary: Time to Bispectral Index 50

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    End point title
    Time to Bispectral Index 50
    End point description
    Throughout the surgical procedure, the propofol target effect-site concentration was to be adjusted to maintain the Bispectral Index (BIS) at 40 to 60. A lower BIS was permissible if the Investigator providing anaesthesia considered it as clinically required for maintenance of adequate anaesthesia.
    End point type
    Secondary
    End point timeframe
    A stopwatch was used to assess the time to BIS 50. The start of the stopwatch coincided directly with initiation of infusion of the study drug. The time to BIS 50 was taken at the first occasion BIS 50 was recorded on the BIS monitor.
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    34
    35
    Units: Minutes
        arithmetic mean (standard deviation)
    3.6089 ± 1.95474
    4.5033 ± 2.72717
    No statistical analyses for this end point

    Secondary: Predicted Effect-site Propofol Concentrations at Time of LOER

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    End point title
    Predicted Effect-site Propofol Concentrations at Time of LOER
    End point description
    Patient-level predicted effect-site propofol concentrations were extracted from the infusion pump data.
    End point type
    Secondary
    End point timeframe
    Measured after initiation of infusion of the study drug at the timepoint where the LOER occured.
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    33
    34
    Units: µg/ml
        arithmetic mean (standard deviation)
    5.088 ± 0.4568
    5.143 ± 0.6714
    No statistical analyses for this end point

    Secondary: Predicted Effect-site Propofol Concentrations at Time of BIS 50

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    End point title
    Predicted Effect-site Propofol Concentrations at Time of BIS 50
    End point description
    Patient-level predicted effect-site propofol concentrations were extracted from the infusion pump data.
    End point type
    Secondary
    End point timeframe
    Measured at the timepoint where the BIS 50 value was recorded on the BIS monitor for the 1st occasion after initiation of infusion of the study drug.
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    33
    33
    Units: µg/ml
        arithmetic mean (standard deviation)
    5.122 ± 0.4547
    5.454 ± 0.857
    No statistical analyses for this end point

    Secondary: Plasma Propofol Concentration 2 (+/- 1) minutes after infusion start

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    End point title
    Plasma Propofol Concentration 2 (+/- 1) minutes after infusion start
    End point description
    Secondary Pharmacokinetic (PK) outcome variables
    End point type
    Secondary
    End point timeframe
    2 (+/- 1) minutes after infusion start
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    30 [3]
    26 [4]
    Units: µg/ml
        median (inter-quartile range (Q1-Q3))
    3.4 (2.3 to 4.7)
    3.4 (2.6 to 4.3)
    Notes
    [3] - PK analysis set
    [4] - PK analysis set
    No statistical analyses for this end point

    Secondary: Plasma Propofol Concentration 10 (+/- 2) minutes after infusion start

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    End point title
    Plasma Propofol Concentration 10 (+/- 2) minutes after infusion start
    End point description
    Secondary PK outcome variables
    End point type
    Secondary
    End point timeframe
    10 (+/- 2) minutes after infusion start
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    20
    17
    Units: µg/ml
        median (inter-quartile range (Q1-Q3))
    4.05 (2.75 to 5)
    5.5 (4.2 to 6.1)
    No statistical analyses for this end point

    Secondary: Plasma Propofol Concentration 10 minutes after achieving target concentration

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    End point title
    Plasma Propofol Concentration 10 minutes after achieving target concentration
    End point description
    Secondary PK outcome variables
    End point type
    Secondary
    End point timeframe
    10 minutes after achieving target concentration
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    22
    22
    Units: µg/ml
        median (inter-quartile range (Q1-Q3))
    4.45 (3.5 to 5.6)
    4.3 (3.5 to 6.4)
    No statistical analyses for this end point

    Secondary: Plasma Propofol Concentration 30 minutes after achieving target concentration

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    End point title
    Plasma Propofol Concentration 30 minutes after achieving target concentration
    End point description
    Secondary PK outcome variables
    End point type
    Secondary
    End point timeframe
    30 minutes after achieving target concentration
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    14
    14
    Units: µg/ml
        median (inter-quartile range (Q1-Q3))
    4.45 (3.3 to 5.8)
    4.35 (3.4 to 5.3)
    No statistical analyses for this end point

    Secondary: Maximum percent change in mean arterial pressure (MAP) from Baseline to Time of LOER

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    End point title
    Maximum percent change in mean arterial pressure (MAP) from Baseline to Time of LOER
    End point description
    MAP = DBP + (SBP - DBP)/3 rounded to the nearest integer, where SBP = systolic blood pressure and DBP = diastolic blood pressure. Baseline is defined as the last non-missing measurement taken prior to the initiation of study drug infusion. The first MAP measurement after LOER was considered as the value at LOER.
    End point type
    Secondary
    End point timeframe
    From baseline to time of LOER
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    33 [5]
    35 [6]
    Units: Percent
        arithmetic mean (standard deviation)
    -9.39 ± 14.622
    -7.09 ± 17.167
    Notes
    [5] - Safety analysis set
    [6] - Safety analysis set
    No statistical analyses for this end point

    Secondary: Maximum percent change in heart rate from Baseline to Time of LOER

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    End point title
    Maximum percent change in heart rate from Baseline to Time of LOER
    End point description
    Baseline is defined as the last non-missing measurement taken prior to the initiation of study drug infusion. Heart rate (beats/minute) was based on the measurement of pulse rate. The first pulse rate measurement after LOER was considered as the value of heart rate at time of LOER.
    End point type
    Secondary
    End point timeframe
    From baseline to time of LOER
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    33
    35
    Units: Percent
        arithmetic mean (standard deviation)
    -4.99 ± 13.434
    -3.62 ± 15.95
    No statistical analyses for this end point

    Secondary: Pain Score for Facial Expression 1 min after start of infusion

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    End point title
    Pain Score for Facial Expression 1 min after start of infusion
    End point description
    Pain score of facial expression: Score 0 - if the subject has a relaxed face, makes eye contact, shows interest in surroundings; Score 1 - if the subject has a worried facial expression, with eyebrows lowered, eyes partially closed, cheeks raised, mouth pursed; Score 2 - if the subject has deep furrows in the forehead, closed eyes, an open mouth, deep lines around nose and lips.
    End point type
    Secondary
    End point timeframe
    1 min after start of infusion
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    35
    35
    Units: Number of subjects with available result
        Score 0
    22
    16
        Score 1
    9
    7
        Score 2
    3
    12
    No statistical analyses for this end point

    Secondary: Pain Score for Facial Expression 6 min after start of infusion

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    End point title
    Pain Score for Facial Expression 6 min after start of infusion
    End point description
    Pain score of facial expression: Score 0 - if the subject has a relaxed face, makes eye contact, shows interest in surroundings; Score 1 - if the subject has a worried facial expression, with eyebrows lowered, eyes partially closed, cheeks raised, mouth pursed; Score 2 - if the subject has deep furrows in the forehead, closed eyes, an open mouth, deep lines around nose and lips.
    End point type
    Secondary
    End point timeframe
    6 min after start of infusion
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    35
    35
    Units: Number of subjects with available result
        Score 0
    1
    1
        Score 1
    0
    0
        Score 2
    0
    0
    No statistical analyses for this end point

    Secondary: Pain Score for Motor Response to Light Pressure 1 min after start of infusion

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    End point title
    Pain Score for Motor Response to Light Pressure 1 min after start of infusion
    End point description
    Pain score of motor response to light pressure at site of or proximal to venous cannula where the study drug was infused: Score 0 - if there is no response; Score 1 - if the subject withdraws or guards the infusion site; Score 2 - if spontaneous motor response (withdraws or guards the injection without light pressure).
    End point type
    Secondary
    End point timeframe
    1 min after start of infusion
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    35
    35
    Units: Number of subjects with available result
        Score 0
    23
    13
        Score 1
    4
    11
        Score 2
    7
    11
    No statistical analyses for this end point

    Secondary: Pain Score for Motor Response to Light Pressure 6 min after start of infusion

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    End point title
    Pain Score for Motor Response to Light Pressure 6 min after start of infusion
    End point description
    Pain score of motor response to light pressure at site of or proximal to venous cannula where the study drug was infused: Score 0 - if there is no response; Score 1 - if the subject withdraws or guards the infusion site; Score 2 - if spontaneous motor response (withdraws or guards the injection without light pressure).
    End point type
    Secondary
    End point timeframe
    6 min after start of infusion
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    35
    35
    Units: Number of subjects with available result
        Score 0
    0
    1
        Score 1
    1
    0
        Score 2
    0
    0
    No statistical analyses for this end point

    Secondary: Pain Score for Verbal Response 1 min after start of infusion

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    End point title
    Pain Score for Verbal Response 1 min after start of infusion
    End point description
    Pain score of verbal response to light pressure at site of or proximal to venous cannula where the study drug was infused : Score 0 - if there is no verbal response; Score 1 - if the subject makes any sound or verbalisation; Score 2 - if spontaneous verbal expression of pain (without light pressure).
    End point type
    Secondary
    End point timeframe
    1 min after start of infusion
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    35
    35
    Units: Number of subjects with available result
        Score 0
    16
    13
        Score 1
    7
    6
        Score 2
    11
    16
    No statistical analyses for this end point

    Secondary: Pain Score for Verbal Response 6 min after start of infusion

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    End point title
    Pain Score for Verbal Response 6 min after start of infusion
    End point description
    Pain score of verbal response to light pressure at site of or proximal to venous cannula where the study drug was infused: Score 0 - if there is no verbal response; Score 1 - if the subject makes any sound or verbalisation; Score 2 - if spontaneous verbal expression of pain (without light pressure).
    End point type
    Secondary
    End point timeframe
    6 min after start of infusion
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    35
    35
    Units: Number of subjects with available result
        Score 0
    1
    1
        Score 1
    0
    0
        Score 2
    0
    0
    No statistical analyses for this end point

    Secondary: Time to Spontaneous Eye Opening

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    End point title
    Time to Spontaneous Eye Opening
    End point description
    Time to eye opening (minutes) was derived based on the time of eye opening relative to termination time of study drug infusion. Time to spontaneous eye opening (minutes) = (date/time of spontaneous eye opening – date/time of termination of study drug infusion).
    End point type
    Secondary
    End point timeframe
    From termination of study drug infusion until spontaneous eye opening
    End point values
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Number of subjects analysed
    35
    35
    Units: Minutes
        arithmetic mean (standard deviation)
    24.7 ± 11.87
    19.7 ± 12.84
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The period of observation lasted from the day the patient signed the Informed Consent until the last follow-up visit. The Investigator had to report any SAE without undue delay within 24 hours following first awareness of the event.
    Adverse event reporting additional description
    In this study, all AEs/SAEs were documented, but only treatment-emergent adverse events (TEAEs), i.e. AEs that started or worsened in severity at or after the initiation of study drug infusion till the end of the study, including the Follow-up Visit, were reported and summarized in tables.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Propofol 2% (20 mg/mL) MCT Fresenius
    Reporting group description
    -

    Reporting group title
    Diprivan 20 mg/mL (AstraZeneca)
    Reporting group description
    -

    Serious adverse events
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 35 (2.86%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Post procedural haemorrhage
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Propofol 2% (20 mg/mL) MCT Fresenius Diprivan 20 mg/mL (AstraZeneca)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    31 / 35 (88.57%)
    31 / 35 (88.57%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    9 / 35 (25.71%)
    4 / 35 (11.43%)
         occurrences all number
    9
    4
    Haematoma
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Immune system disorders
    Iodine allergy
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Hyperthermia
         subjects affected / exposed
    3 / 35 (8.57%)
    4 / 35 (11.43%)
         occurrences all number
    3
    4
    Fatigue
         subjects affected / exposed
    4 / 35 (11.43%)
    1 / 35 (2.86%)
         occurrences all number
    4
    1
    Infusion site pain
         subjects affected / exposed
    2 / 35 (5.71%)
    2 / 35 (5.71%)
         occurrences all number
    2
    2
    Injection site pain
         subjects affected / exposed
    1 / 35 (2.86%)
    3 / 35 (8.57%)
         occurrences all number
    1
    3
    Malaise
         subjects affected / exposed
    1 / 35 (2.86%)
    3 / 35 (8.57%)
         occurrences all number
    1
    3
    Pyrexia
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    2
    Asthenia
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Chills
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Hypothermia
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Injection site haematoma
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 35 (2.86%)
    2 / 35 (5.71%)
         occurrences all number
    1
    2
    Agitation
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    Depression
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Penile pain
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Procedural pain
         subjects affected / exposed
    10 / 35 (28.57%)
    13 / 35 (37.14%)
         occurrences all number
    10
    13
    Post procedural swelling
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Wound complication
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    2
    Blood pressure increased
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Blood urine
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Blood urine present
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Oxygen saturation decreased
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Respiratory rate decreased
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Transaminases increased
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    Syncope
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 35 (5.71%)
    3 / 35 (8.57%)
         occurrences all number
    2
    3
    Gastrointestinal disorders
    Dysphagia
         subjects affected / exposed
    8 / 35 (22.86%)
    8 / 35 (22.86%)
         occurrences all number
    8
    8
    Nausea
         subjects affected / exposed
    7 / 35 (20.00%)
    6 / 35 (17.14%)
         occurrences all number
    7
    6
    Vomiting
         subjects affected / exposed
    5 / 35 (14.29%)
    5 / 35 (14.29%)
         occurrences all number
    5
    5
    Constipation
         subjects affected / exposed
    2 / 35 (5.71%)
    3 / 35 (8.57%)
         occurrences all number
    2
    3
    Abdominal Pain
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    Diarrhoea
         subjects affected / exposed
    2 / 35 (5.71%)
    0 / 35 (0.00%)
         occurrences all number
    2
    0
    Abdominal distension
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Abdominal hernia
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Dyspepsia
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    Dysuria
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Haematuria
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 35 (2.86%)
    1 / 35 (2.86%)
         occurrences all number
    1
    1
    Cold sweat
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Erythema
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Urticaria
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 35 (5.71%)
    3 / 35 (8.57%)
         occurrences all number
    2
    3
    Neck pain
         subjects affected / exposed
    1 / 35 (2.86%)
    4 / 35 (11.43%)
         occurrences all number
    1
    4
    Pain in extremity
         subjects affected / exposed
    1 / 35 (2.86%)
    3 / 35 (8.57%)
         occurrences all number
    1
    3
    Musculoskeletal pain
         subjects affected / exposed
    2 / 35 (5.71%)
    1 / 35 (2.86%)
         occurrences all number
    2
    1
    Arthralgia
         subjects affected / exposed
    0 / 35 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    2
    Myalgia
         subjects affected / exposed
    1 / 35 (2.86%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 35 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1

    More information

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    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.
    Only a descriptive comparison of the primary endpoint (time to LOER) between test and reference treatment was performed. Therefore, no statistical inference was taken.
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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