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   43845   clinical trials with a EudraCT protocol, of which   7282   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:
    The effect of the popliteal plexus block on postoperative pain after total knee arthroplasty - a randomized, controlled, double-blinded study

    Summary
    EudraCT number
    		 2017-005180-40
    Trial protocol
    		 DK  
    Global end of trial date
    23 Aug 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Nov 2019
    First version publication date
    11 Nov 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    Protocol_PPB_TKA_31122017
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03439787
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Aarhus University Hospital
    Sponsor organisation address
    Palle-Juul Jensens Boulevard, Aarhus N, Denmark, 8200
    Public contact
    Bedøvelse og Operation Nord Thomas Fichtner Bendtsen, Aarhus University Hospital, +45 51542997, tfb@dadlnet.dk
    Scientific contact
    Bedøvelse og Operation Nord Thomas Fichtner Bendtsen, Aarhus University Hospital, +45 51542997, tfb@dadlnet.dk
    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
    10 Sep 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Aug 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Aug 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the analgesic effect of the popliteal plexus block (PPB) as a supplement to a femoral triangle block (FTB) after total knee arthroplasty (TKA)
    Protection of trial subjects
    The trial was conducted in accordance with the Declaration of Helsinki and approved by the Danish Medicines Agency, The Central Denmark Region Committees on Health Research Ethics and the Danish Data Protection Agency. The trial was prospectively registered in the EudraCT database and was monitored by the Good Clinical Practice Unit at Aalborg and Aarhus University Hospitals. Prior to inclusion, written informed consent was obtained from all subjects.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 May 2018
    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
    Denmark: 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)
    4
    From 65 to 84 years
    11
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients recruited at Silkeborg Regional Hospital in Denmark from the outpatient clinic according to the approved recruitment plan in the protocol

    Pre-assignment
    Screening details
    		 49 patients screened from May 15 2018 to August 23 2018 Screening based on in- and exclusion criteria defined in the approved protocol

    Period 1
    Period 1 title
    overall period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Intervention group
    Arm description
    		 Patients with NRS > 3 in the postoperative observation period received a PPB. Popliteal plexus block with 10 ml of Marcaine 5 mg/ml with adrenaline 5 microgram/ml + 0.5 ml dexamethasone 4 mg/ml
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Bupivacaine-epinephrine
    Investigational medicinal product code
    Other name
    Marcain-adrenaline
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Perineural use
    Dosage and administration details
    Each patient randomized to this arm was administered one popliteal plexus block with 10 ml Marcain 5 mg/ml with adrenaline 5 microgram/ml + 0.5 ml dexamethasone 4 mg/ml.

    Arm title
    		 Placebo group
    Arm description
    		 Patients with NRS > 3 in the postoperative observation period received a popliteal plexus block. Popliteal plexus block with 10 ml sodium chloride 0.9 %
    Arm type
    		 Placebo

    Investigational medicinal product name
    Sodium chloride 0.9 %
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Perineural use
    Dosage and administration details
    Each patient randomized to this arm received one popliteal plexus block with 10 ml sodium chloride 0.9 %

    Arm title
    		 No intervention (no PPB)
    Arm description
    		 If the patient does not report NRS > 3 during the 3-hour observation period, the patient will not receive a PPB.
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Intervention group Placebo group No intervention (no PPB)
    Started
    4
    4
    7
    Completed
    4
    4
    7

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Intervention group
    Reporting group description
    		 Patients with NRS > 3 in the postoperative observation period received a PPB. Popliteal plexus block with 10 ml of Marcaine 5 mg/ml with adrenaline 5 microgram/ml + 0.5 ml dexamethasone 4 mg/ml

    Reporting group title
    Placebo group
    Reporting group description
    		 Patients with NRS > 3 in the postoperative observation period received a popliteal plexus block. Popliteal plexus block with 10 ml sodium chloride 0.9 %

    Reporting group title
    No intervention (no PPB)
    Reporting group description
    		 If the patient does not report NRS > 3 during the 3-hour observation period, the patient will not receive a PPB.

    Reporting group values
    		 Intervention group Placebo group No intervention (no PPB) Total
    Number of subjects
    		 4 4 7 15
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 1 0 3 4
        From 65-84 years
    		 3 4 4 11
    Gender categorical
    Units: Subjects
        Female
    		 3 3 3 9
        Male
    		 1 1 4 6

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Intervention group
    Reporting group description
    		 Patients with NRS > 3 in the postoperative observation period received a PPB. Popliteal plexus block with 10 ml of Marcaine 5 mg/ml with adrenaline 5 microgram/ml + 0.5 ml dexamethasone 4 mg/ml

    Reporting group title
    Placebo group
    Reporting group description
    		 Patients with NRS > 3 in the postoperative observation period received a popliteal plexus block. Popliteal plexus block with 10 ml sodium chloride 0.9 %

    Reporting group title
    No intervention (no PPB)
    Reporting group description
    		 If the patient does not report NRS > 3 during the 3-hour observation period, the patient will not receive a PPB.

    Primary: Success of the PPB

    		 Close Top of page
    End point title
    		 Success of the PPB [1] [2]
    End point description
    Success of the PPB is defined as the proportion of patients with significant postoperative pain (NRS > 3) after FTB, who drop in pain score to NRS ≤ 3 after PPB and maintain NRS ≤ 3 without any opioids until 60 minutes after PPB. No data available as this trial was terminated early and no statistical analyses have been performed.
    End point type
    Primary
    End point timeframe
    Up until 60 minutes after PPB
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No statistical analyses have been performed as the trial was terminated early due to problems in the study design. The Danish Medicines Agency and the Central Denmark Region Committees on Health Research Ethics were notified after this early termination. The termination was only due to problems in the study design and not related to any safety concerns regarding the patients.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point can only be assessed in patients receiving a popliteal plexus block - and not for the non intervention group where the patients did not receive a popliteal plexus block.
    End point values
    		 Intervention group Placebo group
    Number of subjects analysed
    0 [3]
    0 [4]
    Units: yes/no
    Notes
    [3] - No statistical analysis performed at the trial was terminated early.
    [4] - No statistical analysis performed at the trial was terminated early.
    No statistical analyses for this end point

    Secondary: Onset time of the PPB

    		 Close Top of page
    End point title
    		 Onset time of the PPB [5]
    End point description
    The onset time is defined as the time from withdrawal of the block needle and until the patient reports NRS ≤ 3. The maximal onset time is defined as 60 minutes. The pain scores after PPB are evaluated every 5 minutes until 15 minutes after PPB and hereafter every 15 minutes until 60 minutes after PPB.
    End point type
    Secondary
    End point timeframe
    The pain scores after PPB are evaluated every 5 minutes until 15 minutes after PPB and hereafter every 15 minutes until 60 minutes after PPB.
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point can only be assessed in patients receiving a popliteal plexus block - and not for the non intervention group where the patients did not receive a popliteal plexus block.
    End point values
    		 Intervention group Placebo group
    Number of subjects analysed
    0 [6]
    0 [7]
    Units: NRS scale 0-10
    Notes
    [6] - No statistical analysis performed at the trial was terminated early.
    [7] - No statistical analysis performed at the trial was terminated early.
    No statistical analyses for this end point

    Secondary: The effect of the PPB on cutaneous sensation on the lateral aspect of the lower leg

    		 Close Top of page
    End point title
    		 The effect of the PPB on cutaneous sensation on the lateral aspect of the lower leg [8]
    End point description
    Sensation is graded on a 3-point scale: 0 = no sensation, 1 = reduced sensation and 2 = normal sensation to pinprick compared to the contralateral side
    End point type
    Secondary
    End point timeframe
    Cutaneous sensation is evaluated with a pinprick test. The pinprick test is performed at baseline and 2 hours after the placement of the PPB, t,PPB = 2 hours
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point can only be assessed in patients receiving a popliteal plexus block - and not for the non intervention group where the patients did not receive a popliteal plexus block.
    End point values
    		 Intervention group Placebo group
    Number of subjects analysed
    0 [9]
    0 [10]
    Units: 0-3
    Notes
    [9] - No statistical analysis performed at the trial was terminated early.
    [10] - No statistical analysis performed at the trial was terminated early.
    No statistical analyses for this end point

    Secondary: The effect of PPB on isometric muscle strength of the dorso- and plantar flexors of the ankle joint

    		 Close Top of page
    End point title
    		 The effect of PPB on isometric muscle strength of the dorso- and plantar flexors of the ankle joint [11]
    End point description
    Dorsal and plantar flexion of the foot is measured with a handheld dynamometer as the maximum isometric contraction (MVIC). The test is performed at baseline and 2 hours after the placement of the PPB. The highest value of three consecutive MVIC measurements, separated by a minimum of 30 seconds, is registered.
    End point type
    Secondary
    End point timeframe
    Measured at baseline and 3 hours after popliteal plexus block
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point can only be assessed in patients receiving a popliteal plexus block - and not for the non intervention group where the patients did not receive a popliteal plexus block.
    End point values
    		 Intervention group Placebo group
    Number of subjects analysed
    0 [12]
    0 [13]
    Units: Newton
        number (not applicable)
    Notes
    [12] - No statistical analysis performed at the trial was terminated early.
    [13] - No statistical analysis performed at the trial was terminated early.
    No statistical analyses for this end point

    Secondary: Cumulated opioid consumption from 0-4 hours

    		 Close Top of page
    End point title
    		 Cumulated opioid consumption from 0-4 hours [14]
    End point description
    Opioid consumption is registered from the electronic patient record (EPJ) and entered into REDCap.
    End point type
    Secondary
    End point timeframe
    0-4 hours
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point can only be assessed in patients receiving a popliteal plexus block - and not for the non intervention group where the patients did not receive a popliteal plexus block.
    End point values
    		 Intervention group Placebo group
    Number of subjects analysed
    0 [15]
    0 [16]
    Units: mg
        number (not applicable)
    Notes
    [15] - No statistical analysis performed at the trial was terminated early.
    [16] - No statistical analysis performed at the trial was terminated early.
    No statistical analyses for this end point

    Secondary: Cumulated opioid consumption from 4-24 hours

    		 Close Top of page
    End point title
    		 Cumulated opioid consumption from 4-24 hours [17]
    End point description
    End point type
    Secondary
    End point timeframe
    4-24 hours
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point can only be assessed in patients receiving a popliteal plexus block - and not for the non intervention group where the patients did not receive a popliteal plexus block.
    End point values
    		 Intervention group Placebo group
    Number of subjects analysed
    0 [18]
    0 [19]
    Units: mg
        number (not applicable)
    Notes
    [18] - No statistical analysis performed at the trial was terminated early.
    [19] - No statistical analysis performed at the trial was terminated early.
    No statistical analyses for this end point

    Secondary: Pain scores

    		 Close Top of page
    End point title
    		 Pain scores [20]
    End point description
    For subjects receiving a PPB, pain scores will be performed at 2, 4 and 24 hours after PPB. The patient is asked about the worst pain since last test time. For subjects not receiving a PPB, final pain scores will be made at the follow-up visit after 24 hours.
    End point type
    Secondary
    End point timeframe
    2, 4 and 24 hours after PPB
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This end point can only be assessed in patients receiving a popliteal plexus block - and not for the non intervention group where the patients did not receive a popliteal plexus block.
    End point values
    		 Intervention group Placebo group
    Number of subjects analysed
    0 [21]
    0 [22]
    Units: NRS 0-10
    Notes
    [21] - No statistical analysis performed at the trial was terminated early.
    [22] - No statistical analysis performed at the trial was terminated early.
    No statistical analyses for this end point

    Secondary: The number of patients experiencing significant pain (NRS > 3) as a proportion of all patients with FTB

    		 Close Top of page
    End point title
    		 The number of patients experiencing significant pain (NRS > 3) as a proportion of all patients with FTB
    End point description
    All patients receive a FTB and are observed postoperatively for the development of significant pain (NRS > 3) during an observation period defined as: A 3-hour observation period starting at the return of normal cutaneous sensation after spinal anaesthesia. Normal cutaneous sensation is defined as a pinprick score of 2 on both the lateral thigh and the lateral aspect of the lower leg.
    End point type
    Secondary
    End point timeframe
    A 3-hour observation period starting at the return of normal cutaneous sensation after spinal anaesthesia.
    End point values
    		 Intervention group Placebo group No intervention (no PPB)
    Number of subjects analysed
    0 [23]
    0 [24]
    0 [25]
    Units: Frequency
    Notes
    [23] - No statistical analysis performed at the trial was terminated early.
    [24] - No statistical analysis performed at the trial was terminated early.
    [25] - No statistical analysis was done because the trial was terminated early
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From time of block placement (popliteal plexus block) to 24 hours after block placement
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10.0
    Reporting groups
    Reporting group title
    Intervention group
    Reporting group description
    		 Popliteal plexus block with 10 ml of Marcaine 5 mg/ml with adrenaline 5 microgram/ml + 0.5 ml dexamethasone 4 mg/ml

    Reporting group title
    Placebo group
    Reporting group description
    		 Popliteal plexus block with 10 ml sodium chloride 0.9 %

    Reporting group title
    No intervention group
    Reporting group description
    		 -

    Serious adverse events
    		 Intervention group Placebo group No intervention group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Intervention group Placebo group No intervention group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 4 (50.00%)
    2 / 4 (50.00%)
    0 / 7 (0.00%)
    General disorders and administration site conditions
    Nausea
         subjects affected / exposed
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    3
    0
    Dizziness
    Additional description: Mild dizziness when the patient stands up, resolves immediately when the patients lies down.
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0
    Leg cramp
    Additional description: Mild leg cramp
         subjects affected / exposed
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 7 (0.00%)
         occurrences all number
    0
    1
    0
    Shivering
    Additional description: Mild shivering in the early postoperative period
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 7 (0.00%)
         occurrences all number
    1
    0
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Mar 2018
    Amendment approved March 26 2018 by the Ethics Committee and March 21 2018 by the Danish Medicines Agency Amendment: Aarhus University Hospital is added as a center. The randomization is made with envelopes instead of electronic randomization i REDCap. All patients are allowed to receive 8 mg dexamethasone IV at the end of the operation to prevent nausea.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    23 Aug 2018
    At the time of trial termination, 15 patients have been included, and 8 of these patients have received the active PPB and 7 the placebo PPB according to the protocol and randomization. We have become aware of two major issues in the study design, which compromise the validity of the data: 1) Competing pain. Several patients have complained of competing pain from the incision site at the front of the knee. The PPB will only anesthetize pain from the posterior aspect of the knee, but according to the protocol the PPB is given at any pain score above 3. 2) Placebo effect. Performance of the PPB when the patient complains of pain introduces a risk of a placebo effect, where the block procedure itself generates a feeling of pain relief. We did take this into account when designing the study, but we did not expect the placebo effect to continue beyond the first 60 minutes after PPB performance. Data from the 8 patients with active PPB suggest that we have underestimated the placebo effect, which invalidates our primary end point as defined in the protocol. At the time of termination all 15 patients have completed the study according to the protocol. There have been no serious adverse events during the trial period, and we have not experienced any problems regarding the safety of the patients. The decision to terminate the trial is solely based on the problems in the study design, which compromise the validity of the data. Therefore, the most ethical decision is to terminate the trial in its current from instead of using resources on a trial that will not provide valid or relevant data. This trial was terminated and will not be restarted.
    -

    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 Apr 19 00:34:54 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA