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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38185   clinical trials with a EudraCT protocol, of which   6272   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).
     
    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:
    Evaluating the effectiveness of intravenous ciclosporin on reducing reperfusion injury in patients undergoing primary percutaneous coronary intervention: a double-blind, phase II, randomised controlled trial (CAPRI)

    Summary
    EudraCT number
    2014-002628-29
    Trial protocol
    GB  
    Global end of trial date
    11 Nov 2017

    Results information
    Results version number
    v1(current)
    This version publication date
    12 Jul 2019
    First version publication date
    12 Jul 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    R&D6327
    Additional study identifiers
    ISRCTN number
    ISRCTN27767229
    US NCT number
    NCT02390674
    WHO universal trial number (UTN)
    -
    Other trial identifiers
    REC reference: 13/NE/1070
    Sponsors
    Sponsor organisation name
    The Newcastle upon Tyne Hospitals NHS Foundation Trust
    Sponsor organisation address
    Freeman Hospital, Freeman Road, Newcastle upon Tyne, United Kingdom, NE7 7DN
    Public contact
    Professor Ioakim Spyridopoulos, Newcastle University, +44 01912418675, ioakim.spyridopoulos@ncl.ac.uk
    Scientific contact
    Professor Ioakim Spyridopoulos, Newcastle University, +44 01912418675, ioakim.spyridopoulos@ncl.ac.uk
    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
    15 Aug 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Nov 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Nov 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the effect of ciclosporin treatment prior to primary percutaneous coronary intervention on infarct size at 12 weeks relative to placebo treatment.
    Protection of trial subjects
    No action required.
    Background therapy
    All patients received a loading dose of two antiplatelet drugs and heparin before primary PCI. Use of thrombus aspiration and/or glycoprotein IIb/IIIa inhibition was left to the discretion of the treating physician.
    Evidence for comparator
    This was a placebo controlled trial.
    Actual start date of recruitment
    16 Mar 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 52
    Worldwide total number of subjects
    52
    EEA total number of subjects
    52
    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)
    26
    From 65 to 84 years
    24
    85 years and over
    2

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Participants, all of whom had capacity, were recruited from patients with acute myocardial infarction (STEMI) as an emergency at the Freeman Hospital, (Newcastle upon Tyne Hospitals NHS Foundation Trust,) who agreed to undergo treatment by primary percutaneous coronary intervention. Participants were recruited between 05 March 2015 and 21 Dec 2016.

    Pre-assignment
    Screening details
    Potential participants were identified following emergency admission for acute myocardial infarction and agreement to undergo a primary percutaneous intervention (PPCI) procedure. The pregnancy exclusion criterion was assessed verbally due to the emergency nature of myocardial infarction and the need not to delay the standard PPCI procedure.

    Period 1
    Period 1 title
    Randomisation
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Data analyst, Carer, Subject, Assessor
    Blinding implementation details
    Randomisation was conducted by the Newcastle Clinical Trials Unit web system on a 1:1 ratio (ciclosporin:placebo) using random-permuted blocks with random block length. Assignment to either ciclosporin or placebo arm was blinded to both the patient and cardiologist in the cathlab. Preparation of the IMP infusion (ciclosporin or placebo) and randomisation of the patient was performed by unblinded nurses. The infusion bag was placed into a coloured bag to mask any colouration of the solution.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Ciclosporin
    Arm description
    Ciclosporin intravenous infusion of 2.5mg per kilogram of body weight through a catheter positioned within a peripheral vein. Ciclosporin was dissolved in saline (maximum concentration 2.5mg per millilitre).
    Arm type
    Experimental

    Investigational medicinal product name
    Ciclosporin
    Investigational medicinal product code
    Other name
    Sandimmun (concentrate for solution for infusion 50mg/ml), cyclosporin A, cyclosporine
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    Single bolus dose of ciclosporin (2.5mg per kg body weight dissolved in saline, maximum concentration 2.5mg/mL) over 4 minutes immediately prior to reperfusion.

    Arm title
    Placebo
    Arm description
    Placebo (saline) infusion
    Arm type
    Placebo

    Investigational medicinal product name
    Not applicable
    Investigational medicinal product code
    Other name
    Sodium chloride solution
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single infusion over 4 minutes immediately prior to reperfusion (volume to match experimental IMP solution).

    Number of subjects in period 1
    Ciclosporin Placebo
    Started
    26
    26
    Completed
    26
    26
    Period 2
    Period 2 title
    Randomisation to 2 week assessment
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Subject, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Ciclosporin
    Arm description
    Ciclosporin intravenous infusion of 2.5mg per kilogram of body weight through a catheter positioned within a peripheral vein. Ciclosporin was dissolved in saline (maximum concentration 2.5mg per millilitre).
    Arm type
    Experimental

    Investigational medicinal product name
    Ciclosporin
    Investigational medicinal product code
    Other name
    Sandimmun (concentrate for solution for infusion 50mg/ml), cyclosporin A, cyclosporine
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    Single bolus dose of ciclosporin (2.5mg per kg body weight dissolved in saline, maximum concentration 2.5mg/mL) over 4 minutes immediately prior to reperfusion.

    Arm title
    Placebo
    Arm description
    Placebo (saline) infusion
    Arm type
    Placebo

    Investigational medicinal product name
    Not applicable
    Investigational medicinal product code
    Other name
    Sodium chloride solution
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single infusion over 4 minutes immediately prior to reperfusion (volume to match experimental IMP solution).

    Number of subjects in period 2
    Ciclosporin Placebo
    Started
    26
    26
    Completed
    26
    26
    Period 3
    Period 3 title
    2 week assessment to 12 week assessment
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Ciclosporin
    Arm description
    Ciclosporin intravenous infusion of 2.5mg per kilogram of body weight through a catheter positioned within a peripheral vein. Ciclosporin was dissolved in saline (maximum concentration 2.5mg per millilitre).
    Arm type
    Experimental

    Investigational medicinal product name
    Ciclosporin
    Investigational medicinal product code
    Other name
    Sandimmun (concentrate for solution for infusion 50mg/ml), cyclosporin A, cyclosporine
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravascular use
    Dosage and administration details
    Single bolus dose of ciclosporin (2.5mg per kg body weight dissolved in saline, maximum concentration 2.5mg/mL) over 4 minutes immediately prior to reperfusion.

    Arm title
    Placebo
    Arm description
    Placebo (saline) infusion
    Arm type
    Placebo

    Investigational medicinal product name
    Not applicable
    Investigational medicinal product code
    Other name
    Sodium chloride solution
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single infusion over 4 minutes immediately prior to reperfusion (volume to match experimental IMP solution).

    Number of subjects in period 3
    Ciclosporin Placebo
    Started
    26
    26
    Completed
    26
    26

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Ciclosporin
    Reporting group description
    Ciclosporin intravenous infusion of 2.5mg per kilogram of body weight through a catheter positioned within a peripheral vein. Ciclosporin was dissolved in saline (maximum concentration 2.5mg per millilitre).

    Reporting group title
    Placebo
    Reporting group description
    Placebo (saline) infusion

    Reporting group values
    Ciclosporin Placebo Total
    Number of subjects
    26 26 52
    Age categorical
    Patients who have been admitted as an emergency for acute myocardial infarction and agreed to undergo a primary percutaneous coronary intervention procedure
    Units: Subjects
        Adults (18-64 years)
    16 10 26
        From 65-84 years
    8 16 24
        85 years and over
    2 0 2
    Gender categorical
    Units: Subjects
        Female
    2 6 8
        Male
    24 20 44
    Diabetes
    Number of participants with diabetes
    Units: Subjects
        Yes
    2 2 4
        No
    24 24 48
    Smoking status
    Units: Subjects
        Never
    9 9 18
        Past
    9 12 21
        Current
    8 5 13
    Medical History: IHD
    Units: Subjects
        Yes
    3 0 3
        No
    23 26 49
    Medical History: COPD
    Units: Subjects
        Yes
    0 2 2
        No
    26 24 50
    Medical history: PVD
    Units: Subjects
        Yes
    0 1 1
        No
    26 25 51
    Other relevant medical history
    No previous history of MI, CVA/TIA, PCI was recorded in either group
    Units: Subjects
        Yes
    11 6 17
        No
    15 20 35
    Medication pre-admission - Aspirin
    Units: Subjects
        Yes
    1 4 5
        No
    25 22 47
    Medication pre-admission - Betablocker
    Units: Subjects
        Yes
    2 1 3
        No
    24 25 49
    Medication pre-admission - ACEi or ARB
    Units: Subjects
        Yes
    6 2 8
        No
    20 24 44
    Medication pre-admission - Diuretic
    Units: Subjects
        Yes
    1 3 4
        No
    25 23 48
    Medication pre-admission - Statin
    Units: Subjects
        Yes
    6 6 12
        No
    20 20 40
    Medication pre-admission - Ca Blocker
    Units: Subjects
        Yes
    3 4 7
        No
    23 22 45
    Medication pre-admission - Nitrates
    Units: Subjects
        Yes
    1 0 1
        No
    25 26 51
    Medication pre-admission - Nicorandil
    Units: Subjects
        Yes
    1 0 1
        No
    25 26 51
    ECG - infarct location
    Units: Subjects
        Non-anterior
    18 18 36
        Anterior
    8 8 16
    Pre-interventional medication - Aspirin
    Units: Subjects
        Yes
    26 26 52
        No
    0 0 0
    Pre-interventional medication - Clopidogrel
    Units: Subjects
        Yes
    4 1 5
        No
    22 25 47
    Pre-interventional medication - Prasugrel
    Units: Subjects
        Yes
    19 21 40
        No
    7 5 12
    Pre-interventional medication - Ticagrelor
    Units: Subjects
        Yes
    3 4 7
        No
    23 22 45
    Pre-interventional medication - Abciximab
    Units: Subjects
        Yes
    1 0 1
        No
    25 26 51
    Pre-interventional medication - Tirofiban
    Units: Subjects
        Yes
    19 15 34
        No
    7 11 18
    Pre-interventional medication - Bivalirudin
    Units: Subjects
        Yes
    0 0 0
        No
    26 26 52
    Pre-interventional medication - Heparin
    Units: Subjects
        Yes
    26 26 52
        No
    0 0 0
    Heparin units <=5000
    Units: Subjects
        Yes
    19 17 36
        No
    7 9 16
    Pre-interventional medication - Heparin units >5000
    Units: Subjects
        Yes
    7 9 16
        No
    19 17 36
    PCI-related parameters - Culprit lesion
    Units: Subjects
        Culprit Lesion - LAD
    8 7 15
        Culprit Lesion - LCx
    7 4 11
        Culprit Lesion - RCA
    11 15 26
    PCI-related parameters - TIMI flow before
    Units: Subjects
        TIMI flow before = 0
    25 18 43
        TIMI flow before = 1
    1 8 9
        TIMI flow before = 2
    0 0 0
        TIMI flow before = 3
    0 0 0
    PCI-related parameters - TIMI flow post
    Units: Subjects
        TIMI flow post = 0
    0 0 0
        TIMI flow post = 1
    0 2 2
        TIMI flow post = 2
    0 0 0
        TIMI flow post = 3
    26 24 50
    BMI
    Units: Score
        median (inter-quartile range (Q1-Q3))
    28.7 (24 to 31) 28.2 (24.1 to 31.7) -
    PCI procedure = onset to balloon
    Units: minutes
        arithmetic mean (standard deviation)
    202 ± 98.6 179.8 ± 85.5 -
    PCI procedure - call to balloon
    Units: minutes
        arithmetic mean (standard deviation)
    74.2 ± 26.2 74.1 ± 37 -
    PCI procedure - Door to balloon
    Units: minutes
        arithmetic mean (standard deviation)
    29.3 ± 10.4 30.8 ± 15.5 -
    PCI procedure - onset of symptoms to reperfusion
    Units: minutes
        arithmetic mean (standard deviation)
    204.8 ± 98.8 187.1 ± 80.0 -
    PCI procedure - Target vessel diameter
    Units: mm
        arithmetic mean (standard deviation)
    3.7 ± 0.4 3.5 ± 0.5 -
    PCI procedure - Target vessel stent length
    Units: mm
        arithmetic mean (standard deviation)
    41.9 ± 24.2 40.0 ± 22.8 -
    PCI procedure - Troponin at admission (0 hrs)
    Units: ng/L
        arithmetic mean (standard deviation)
    124.6 ± 210.5 123.7 ± 206.1 -
    Renal function - Glomerular filtration rate
    Units: mL/min
        arithmetic mean (standard deviation)
    87.3 ± 24.9 87.0 ± 25.1 -
    Renal function - Contrast volume per GFR (ml)
    Units: mL
        arithmetic mean (standard deviation)
    154.2 ± 58.6 132.9 ± 51.9 -
    Renal function - Urea at day 0
    Units: mmol/L
        arithmetic mean (standard deviation)
    5.7 ± 1.4 5.9 ± 2.9 -
    Renal function - creatinine at day 0
    Units: umol/L
        arithmetic mean (standard deviation)
    85.2 ± 17.7 83.7 ± 25.6 -
    T Lymphocyte count at baseline (0 minutes) total (CD45)
    Units: Count
        arithmetic mean (standard deviation)
    2068 ± 691 1842 ± 935 -
    T Lymphocyte count at baseline (0 minutes) B-cells (CD-19)
    Units: Count
        arithmetic mean (standard deviation)
    201 ± 107 239 ± 332 -
    T Lymphocyte count at baseline (0 minutes) Natural Killer Cells
    Units: Count
        arithmetic mean (standard deviation)
    500 ± 295 423 ± 275 -
    T Lymphocyte count at baseline (0 minutes) T-cells (CD3)
    Units: Count
        arithmetic mean (standard deviation)
    1350 ± 540 1169 ± 688 -
    T Lymphocyte count at baseline (0 minutes) CD4
    Units: Count
        arithmetic mean (standard deviation)
    785 ± 294 785 ± 532 -
    T Lymphocyte count at baseline (0 mins) CD8
    Units: Count
        arithmetic mean (standard deviation)
    504 ± 392 357 ± 267 -
    Time from symptom onset to randomisation
    Units: Minutes
        median (inter-quartile range (Q1-Q3))
    162 (94 to 272) 164 (120 to 277) -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Ciclosporin
    Reporting group description
    Ciclosporin intravenous infusion of 2.5mg per kilogram of body weight through a catheter positioned within a peripheral vein. Ciclosporin was dissolved in saline (maximum concentration 2.5mg per millilitre).

    Reporting group title
    Placebo
    Reporting group description
    Placebo (saline) infusion
    Reporting group title
    Ciclosporin
    Reporting group description
    Ciclosporin intravenous infusion of 2.5mg per kilogram of body weight through a catheter positioned within a peripheral vein. Ciclosporin was dissolved in saline (maximum concentration 2.5mg per millilitre).

    Reporting group title
    Placebo
    Reporting group description
    Placebo (saline) infusion
    Reporting group title
    Ciclosporin
    Reporting group description
    Ciclosporin intravenous infusion of 2.5mg per kilogram of body weight through a catheter positioned within a peripheral vein. Ciclosporin was dissolved in saline (maximum concentration 2.5mg per millilitre).

    Reporting group title
    Placebo
    Reporting group description
    Placebo (saline) infusion

    Primary: Infarct size at 12 weeks post-PPCI

    Close Top of page
    End point title
    Infarct size at 12 weeks post-PPCI
    End point description
    Infarct size at 12 weeks post-PPCI as measured by cardiac magnetic resonance imaging (MRI). Infarct size will be calculated as the percent of infarcted myocardium per left ventricular (LV) mass. Patients with two analysable MRI scans (technical problems with either the MRI scanner or insufficient image quality, meant some MRI scans were not analysable at either 0 or 12 weeks).
    End point type
    Primary
    End point timeframe
    12 weeks post-PPCI
    End point values
    Ciclosporin Placebo
    Number of subjects analysed
    26
    23
    Units: % of infarcted myocardium per LVM
        arithmetic mean (standard deviation)
    9.1 ± 7.0
    9.1 ± 7.0
    Statistical analysis title
    Percentage infarct size post-PPCI at 12 weeks
    Statistical analysis description
    Multiple linear regression showing difference in mean infarct size post-PPCI at 12 weeks.
    Comparison groups
    Ciclosporin v Placebo
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -0.11
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.45
         upper limit
    2.24

    Secondary: Microvascular obstruction after 2-7 days as measured by a single cardiac MRI scan

    Close Top of page
    End point title
    Microvascular obstruction after 2-7 days as measured by a single cardiac MRI scan
    End point description
    Patients with analysable MRI scan at 2-7 days (technical problems with either the MRI scanner or insufficient image quality, meant some MRI scans were not analysable).
    End point type
    Secondary
    End point timeframe
    2-7 days post-PPCI
    End point values
    Ciclosporin Placebo
    Number of subjects analysed
    26
    25
    Units: Microvascular obstruction (mL)
        arithmetic mean (standard deviation)
    1.7 ± 6.4
    1.9 ± 4.0
    No statistical analyses for this end point

    Secondary: Change in T lymphocyte counts at 5 mins

    Close Top of page
    End point title
    Change in T lymphocyte counts at 5 mins
    End point description
    Change in T lymphocyte counts relative to baseline at 5 minutes post-reperfusion
    End point type
    Secondary
    End point timeframe
    5 minutes post-reperfusion
    End point values
    Ciclosporin Placebo
    Number of subjects analysed
    26
    26
    Units: Counts
    arithmetic mean (standard deviation)
        Lymphocytes (total) (CD45)
    2007 ± 734
    1497 ± 660
        B-cells (CD3)
    205 ± 109
    196 ± 231
        NK-cells
    542 ± 318
    329 ± 198
        T-cells (CD3)
    1248 ± 565
    963 ± 534
        CD4
    719 ± 308
    656 ± 415
        CD8
    471 ± 406
    285 ± 212
    Statistical analysis title
    Mean T lymphocyte counts (CD3) at 5 mins
    Statistical analysis description
    Multiple linear regression showing difference in mean T lymphocyte counts (CD3) at 5 mins
    Comparison groups
    Placebo v Ciclosporin
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    142.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    23.9
         upper limit
    260.9

    Secondary: Change in T lymphocyte counts at 15 mins

    Close Top of page
    End point title
    Change in T lymphocyte counts at 15 mins
    End point description
    Change in T lymphocyte counts relative to baseline at 15 minutes post-reperfusion
    End point type
    Secondary
    End point timeframe
    15 minutes post reperfusion
    End point values
    Ciclosporin Placebo
    Number of subjects analysed
    26
    26
    Units: Counts
    arithmetic mean (standard deviation)
        Lymphocytes (total) CD45
    1923 ± 885
    1363 ± 625
        B-cells (CD3)
    197 ± 109
    195 ± 220
        NK cells
    525 ± 289
    273 ± 154
        T-cells (CD3)
    1190 ± 685
    888 ± 522
        CD4
    689 ± 418
    611 ± 413
        CD8
    449 ± 390
    258 ± 206
    Statistical analysis title
    Mean T lymphocyte counts (CD3) at 15 minutes
    Statistical analysis description
    Multiple linear regression showing difference in T lymphocyte counts (CD3) at 15 mins
    Comparison groups
    Ciclosporin v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    150.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -48.6
         upper limit
    348.8

    Secondary: Change in T lymphocyte counts at 30 minutes

    Close Top of page
    End point title
    Change in T lymphocyte counts at 30 minutes
    End point description
    Change in T lymphocyte counts relative to baseline at 30 minutes post-reperfusion
    End point type
    Secondary
    End point timeframe
    30 minutes post-reperfusion
    End point values
    Ciclosporin Placebo
    Number of subjects analysed
    26
    26
    Units: Counts
    arithmetic mean (standard deviation)
        Lymphocytes (total) (CD45)
    1609 ± 675
    1381 ± 798
        B-cells (CD19)
    209 ± 117
    218 ± 305
        NK cells
    386 ± 232
    266 ± 145
        T-cells (CD3)
    1006 ± 506
    886 ± 632
        CD4
    615 ± 316
    638 ± 518
        CD8
    350 ± 282
    233 ± 166
    Statistical analysis title
    Mean T lymphocyte counts (CD3) at 30 mins
    Statistical analysis description
    Multiple linear regression showing difference in mean T lymphocyte counts (CD3) at 30 mins
    Comparison groups
    Placebo v Ciclosporin
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -23.7
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -192.3
         upper limit
    144.8

    Secondary: Change in T lymphocyte counts at 90 mins

    Close Top of page
    End point title
    Change in T lymphocyte counts at 90 mins
    End point description
    Change in T lymphocyte counts relative to baseline at 90 minutes post-reperfusion
    End point type
    Secondary
    End point timeframe
    90 minutes post-reperfusion
    End point values
    Ciclosporin Placebo
    Number of subjects analysed
    26
    26
    Units: Counts
    arithmetic mean (standard deviation)
        Lymphocytes (total) (CD45)
    1302 ± 596
    1331 ± 742
        B-cells (CD19)
    202 ± 113
    210 ± 266
        NK-cells
    242 ± 171
    244 ± 188
        T-cells (CD3)
    852 ± 472
    867 ± 572
        CD4
    591 ± 326
    657 ± 473
        CD8
    241 ± 183
    199 ± 137
    Statistical analysis title
    mean T lymphocyte counts (CD3) at 90 mins
    Statistical analysis description
    Multiple linear regression showing difference in mean T lymphocyte counts (CD3) at 90 mins
    Comparison groups
    Ciclosporin v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -106.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -331.4
         upper limit
    118.4

    Secondary: Change in T lymphocyte counts at 24 hours

    Close Top of page
    End point title
    Change in T lymphocyte counts at 24 hours
    End point description
    Change in T lymphocyte counts relative to baseline at 24 hours post-reperfusion
    End point type
    Secondary
    End point timeframe
    24 hours post-reperfusion
    End point values
    Ciclosporin Placebo
    Number of subjects analysed
    26
    26
    Units: Counts
    arithmetic mean (standard deviation)
        Lymphocytes (total) (CD45)
    2187 ± 717
    1997 ± 971
        B-cells (CD19)
    277 ± 139
    274 ± 235
        NK cells
    248 ± 144
    255 ± 126
        T-cells (CD3)
    1650 ± 569
    1454 ± 838
        CD4
    1111 ± 431
    1001 ± 667
        CD8
    497 ± 213
    415 ± 245
    Statistical analysis title
    Mean B-cell counts (CD19) at 24 hours
    Statistical analysis description
    Multiple linear regression showing difference in mean B-cell counts (CD19) at 24 hours
    Comparison groups
    Ciclosporin v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    32.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -22.5
         upper limit
    86.7
    Statistical analysis title
    Mean NK-cell counts at 24 hours
    Statistical analysis description
    Multiple linear regression showing difference in mean NK-cell counts at 24 hours
    Comparison groups
    Ciclosporin v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    -29.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -103.5
         upper limit
    43.8
    Statistical analysis title
    Mean T lymphocyte counts (CD3) at 24 hours
    Statistical analysis description
    Multiple linear regression showing difference in mean T lymphocyte counts at 24 hours
    Comparison groups
    Ciclosporin v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    57.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -264.3
         upper limit
    379
    Statistical analysis title
    Mean CD4 count at 24 hours
    Statistical analysis description
    Multiple linear regression showing difference in mean CD4 count at 24 hours
    Comparison groups
    Ciclosporin v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    106.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -59.7
         upper limit
    273.2
    Statistical analysis title
    Mean CD8 count at 24 hours
    Statistical analysis description
    Multiple linear regression showing difference in mean CD8 count at 24 hours
    Comparison groups
    Ciclosporin v Placebo
    Number of subjects included in analysis
    52
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    > 0.05
    Method
    ANCOVA
    Parameter type
    Mean difference (final values)
    Point estimate
    32
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -92.9
         upper limit
    156.9

    Other pre-specified: Troponin at 12h post PPCI (ng/L)

    Close Top of page
    End point title
    Troponin at 12h post PPCI (ng/L)
    End point description
    End point type
    Other pre-specified
    End point timeframe
    12 hours
    End point values
    Ciclosporin Placebo
    Number of subjects analysed
    26
    26
    Units: ng/L
        arithmetic mean (standard deviation)
    4304 ± 3241
    3879 ± 2810
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    SAE information for each patient was recorded for the 12 weeks of the RCT. An SAE occurring more than 2 weeks after the ciclosporin was administered will not be reported as CTIMP-related.
    Adverse event reporting additional description
    Renal impairment (creatinine increase ≥25% or ≥0.5mg/dl relative to baseline) in the first 2 weeks can be an adverse event related to either the IMP used in the trial (ciclosporin) or the contrast dye used in the routine PCI procedure (iodixanol or ioversol).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    1
    Reporting groups
    Reporting group title
    Ciclosporin
    Reporting group description
    Ciclosporin intravenous infusion of 2.5mg per kilogram of body weight through a catheter positioned within a peripheral vein. Ciclosporin was dissolved in saline (maximum concentration 2.5mg per millilitre).

    Reporting group title
    Placebo
    Reporting group description
    Placebo (saline) infusion

    Serious adverse events
    Ciclosporin Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 26 (38.46%)
    17 / 26 (65.38%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    0
    Congenital, familial and genetic disorders
    Chest pain
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (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
    Intracranial bleed
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Renal and urinary disorders
    Contrast induced nephropathy
         subjects affected / exposed
    8 / 26 (30.77%)
    15 / 26 (57.69%)
         occurrences causally related to treatment / all
    8 / 8
    14 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clot retention
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Creatinine rose by more than 25% from baseline
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Raised creatinine - drug induced
    Additional description: within normal limits
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MPO vasculitis and AKI
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         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: 0.1%
    Non-serious adverse events
    Ciclosporin Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 26 (15.38%)
    5 / 26 (19.23%)
    Cardiac disorders
    Chest pain
         subjects affected / exposed
    1 / 26 (3.85%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Chronic subdural haematoma
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Inner ear problem
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Non cardiac chest pain
    Additional description: Felt to be due to gall bladder disease
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Collapse
    Additional description: Attributed to bladder problem
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Increase in creatinine from baseline to d=1
    Additional description: Patient had a contrast dose that was >4xGFR volume of contrast. Creatinine improved at d=2
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Chest pain
    Additional description: Chest pain deemed to be muscular skeletal in nature
         subjects affected / exposed
    1 / 26 (3.85%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Diarrhoea
    Additional description: Diarrhoea and temperature, also strong cough
         subjects affected / exposed
    0 / 26 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Aug 2014
    Confirmation that the saline solution used is a UK marketed product. Clarification regarding the immediate reporting of SAEs, SARs and SUSARs by the investigator to the sponsor during drug treatment. Provision for emergency unblinding of the trial.
    14 Jan 2016
    Changes to design of study: − Change of phase from II/III to phase II to avoid potential issue with term ‘pilot’ and CONSORT reporting. − Change of one of the two stratification variables from ‘gender’ to ‘time from symptom onset to randomisation’ as it was felt the outcome would not be dependent on gender. Changes to the procedures undertaken by the patient: − Removal of 60 minute arterial blood sample as only one sample can be taken from sheath remaining from surgery. − Clarification 90 minute arterial blood sample taken on coronary care unit using sheath. − Possible home visit by clinical fellow on day 3 to obtain U&E monitoring sample if patient discharged from hospital prior to day 3 (safety visit). − Addition of optional research blood sample at 2 week visit. Revision of wording of two of the secondary objectives for clarity Definition of how infarct size will be calculated added to primary outcome Details added regarding acquisition of cardiac MRI images and how cardiac MRI images will be analysed Definitions added of clinical endpoints for clarity Contact details amended if problems experienced with randomisation system Removal of integrity of blind check at 12 month visit Definition added regarding resolution of renal SAEs Responsibility for reporting of SUSARs to REC changed from CI to sponsor in line with sponsor SOP Monitoring ‐ percent of source data to be verified and eligibility criteria to be reviewed amended to reflect sponsor approved monitoring plan Trial registration numbers added Addition of 'phase II' to title of study
    20 Oct 2016
    An update to the CAPRI protocol to reflect the current IMP administration procedure and provide additional details regarding blinding. In addition the wording in section 19.2 referring to the Reference Safety Information (RSI) has been amended for clarification purposes. The updated RSI, section 4.8 of the SmPC for Sandimmun Concentrate for Solution for Infusion 50mg/mL dated 09 May 2016, was been submitted as part of the Substantial Amendment to the MHRA for review.

    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
    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA