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   43857   clinical trials with a EudraCT protocol, of which   7284   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:
    Antiplatelet effects of once versus twice daily dosing of aspirin after coronary artery bypass grafting

    Summary
    EudraCT number
    		 2011-002233-19
    Trial protocol
    		 SE  
    Global end of trial date
    01 Jul 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 May 2021
    First version publication date
    07 May 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ASA-CABG-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02482857
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Karolinska Institutet
    Sponsor organisation address
    17177, Stockholm, Sweden,
    Public contact
    Clinical Pharmacology Unit, Karolinska Institutet, 46 851775293, paul.hjemdahl@ki.se
    Scientific contact
    Clinical Pharmacology Unit, Karolinska Institutet, 46 851775293, paul.hjemdahl@ki.se
    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
    01 Jul 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    01 Jul 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Jul 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study is to investigate the impact on platelet function of increasing either the aspirin dose (from 75 mg to 160 mg) or dosing frequency (to 75 mg BID) over 3 months in patients undergoing elective CABG surgery.
    Protection of trial subjects
    he studywas approved by the Regional Ethical ReviewBoard in Stockholm(2011/1074-31/1). Patients are free to withdraw their consent for study treatment and/or consent to participate in the study at any time.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Dec 2011
    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
    Sweden: 42
    Worldwide total number of subjects
    42
    EEA total number of subjects
    42
    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)
    16
    From 65 to 84 years
    26
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients were recruited from Karolinska University Hospital, Sweden, between December 2011 and July 2015.

    Pre-assignment
    Screening details
    		 Patients with stable angina pectoris scheduled to undergo elective CABG were screened. Exlusion criteria were intake of any other platelet inhibitor than ASA during the last seven days prior to surgery, known bleeding disorder or kidney failure, preoperative platelet count outside of the range 100,000–450,000/μL or a haemoglobin level below 80g/L.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ASA 75 mg OD
    Arm description
    		 Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to ASA 75 mg OD up to three months after the operation.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Aspirin
    Investigational medicinal product code
    11423 (for 75 mg)
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to ASA 75 mg OD up to three months after the operation.

    Arm title
    		 ASA 75 mg BID
    Arm description
    		 Patients were treated with ASA 75 mg OD before the CABG surgery, and randomized to 75 mg twice daily (BID) up to three months after the operation.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Aspirin
    Investigational medicinal product code
    11423 (for 75 mg)
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to 75 mg twice daily (BID) up to three months after the operation.

    Arm title
    		 ASA 160 mg OD
    Arm description
    		 Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to 160 mg OD up to three months after the operation.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Aspirin
    Investigational medicinal product code
    11063 (for 160 mg)
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to ASA 160 mg OD up to three months after the operation.

    Number of subjects in period 1
    		ASA 75 mg OD ASA 75 mg BID ASA 160 mg OD
    Started
    11
    14
    17
    Completed
    11
    14
    17

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    ASA 75 mg OD
    Reporting group description
    		 Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to ASA 75 mg OD up to three months after the operation.

    Reporting group title
    ASA 75 mg BID
    Reporting group description
    		 Patients were treated with ASA 75 mg OD before the CABG surgery, and randomized to 75 mg twice daily (BID) up to three months after the operation.

    Reporting group title
    ASA 160 mg OD
    Reporting group description
    		 Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to 160 mg OD up to three months after the operation.

    Reporting group values
    		 ASA 75 mg OD ASA 75 mg BID ASA 160 mg OD Total
    Number of subjects
    		 11 14 17 42
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 69 ± 10 66 ± 7 67 ± 11 -
    Gender categorical
    Units: Subjects
        Female
    		 1 0 0 1
        Male
    		 10 14 17 41
    BMI
    Units: kg/m2
        arithmetic mean (standard deviation)
    		 27 ± 3 29 ± 3 27 ± 2 -
    Blood pressure Systolic
    Units: mm Hg
        arithmetic mean (standard deviation)
    		 131 ± 15 133 ± 20 143 ± 17 -
    Blood pressure Diastolic
    Units: mm Hg
        arithmetic mean (standard deviation)
    		 75 ± 9 77 ± 7 84 ± 6 -
    eGFR
    Estimated Glomerular filtration rate using the Cockroft and Gault equation
    Units: mL/min
        arithmetic mean (standard deviation)
    		 95 ± 36 98 ± 24 85 ± 26 -
    EuroSCORE II
    European System for Cardiac Operative Risk Evaluation Score II.
    Units: Percent
        median (full range (min-max))
    		 2.5 (0.9 to 8.6) 1.7 (0.9 to 4.6) 2.4 (0.9 to 10) -
    History of smoking
    Units: Number (%)
        arithmetic mean (standard deviation)
    		 6 ± 55 7 ± 50 13 ± 76 -
    Hypertension
    Units: Numbers (%)
        arithmetic mean (standard deviation)
    		 8 ± 73 14 ± 100 9 ± 53 -
    Hyperlipidemia
    Units: Number (%)
        arithmetic mean (standard deviation)
    		 11 ± 100 12 ± 86 15 ± 88 -
    Diabetes mellitus
    Units: Number (%)
        arithmetic mean (standard deviation)
    		 4 ± 36 3 ± 21 4 ± 24 -
    Medication Beta blocker
    Units: Number (%)
        arithmetic mean (standard deviation)
    		 7 ± 64 14 ± 100 14 ± 83 -
    Medication ACE inhibitor
    angiotensin converting enzyme
    Units: Number (%)
        arithmetic mean (standard deviation)
    		 5 ± 45 7 ± 50 8 ± 47 -
    Medication Statin
    Units: Number (%)
        arithmetic mean (standard deviation)
    		 10 ± 91 13 ± 93 15 ± 88 -
    Haemoglobin
    Units: g/L
        arithmetic mean (full range (min-max))
    		 139 (115 to 159) 141 (133 to 151) 135 (108 to 150) -
    White blood cell counts
    Units: Counts
        arithmetic mean (full range (min-max))
    		 7 (3.7 to 10.1) 6 (4.5 to 8.5) 7 (5.1 to 9.7) -
    Platelet counts
    Units: Counts
        arithmetic mean (full range (min-max))
    		 226 (138 to 361) 224 (164 to 396) 240 (145 to 326) -
    Mean platelet volume
    Units: Volume
        arithmetic mean (full range (min-max))
    		 8 (6.6 to 9.1) 8 (7.1 to 8.7) 8 (6.2 to 8.3) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ASA 75 mg OD
    Reporting group description
    		 Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to ASA 75 mg OD up to three months after the operation.

    Reporting group title
    ASA 75 mg BID
    Reporting group description
    		 Patients were treated with ASA 75 mg OD before the CABG surgery, and randomized to 75 mg twice daily (BID) up to three months after the operation.

    Reporting group title
    ASA 160 mg OD
    Reporting group description
    		 Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to 160 mg OD up to three months after the operation.

    Primary: Haemoglobin at postop

    		 Close Top of page
    End point title
    		 Haemoglobin at postop
    End point description
    End point type
    Primary
    End point timeframe
    Haemoglobin at discharge (postop) and 1 and 3 months after the operation in patients receiving three dosages of ASA (75 mg OD, 75 mg BID and 160 OD) after discharge.
    End point values
    		 ASA 75 mg OD ASA 75 mg BID ASA 160 mg OD
    Number of subjects analysed
    11
    14
    17
    Units: g/L
    arithmetic mean (full range (min-max))
        Postop
    103 (85 to 114)
    101 (84 to 115)
    99 (82 to 115)
        1 month
    120 (92 to 136)
    125 (113 to 136)
    117 (98 to 132)
        3 months
    136 (110 to 156)
    138 (118 to 147)
    131 (106 to 148)
    Statistical analysis title
    		 Difference Haemoglobin
    Statistical analysis description
    Differences in haemoglobin for within-group differences, compared to preoperative baseline, at discharge (postop) 1- and 3-months postop.
    Comparison groups
    ASA 75 mg OD v ASA 75 mg BID v ASA 160 mg OD
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 ANOVA
    Confidence interval

    Primary: White blood cell counts at postop

    		 Close Top of page
    End point title
    		 White blood cell counts at postop
    End point description
    End point type
    Primary
    End point timeframe
    White blood cell counts at discharge (postop) and 1 and 3 months after the operation in patients receiving three dosages of ASA (75 mg OD, 75 mg BID and 160 OD) after discharge.
    End point values
    		 ASA 75 mg OD ASA 75 mg BID ASA 160 mg OD
    Number of subjects analysed
    11
    14
    17
    Units: 10(6)/L
    arithmetic mean (full range (min-max))
        Postop
    10 (5.5 to 15.4)
    9 (6.4 to 11.0)
    10 (4.3 to 13.6)
        1 month
    8 (5.5 to 9.9)
    7 (4.9 to 9.8)
    8 (5.7 to 9.5)
        3 months
    7 (4.0 to 9.9)
    6 (4.5 to 9.5)
    7 (5.4 to 8.3)
    Statistical analysis title
    		 Difference White blood cell counts
    Statistical analysis description
    Differences in white blood cell counts for within-group differences, compared to preoperative baseline, at discharge (postop) 1- and 3-months postop.
    Comparison groups
    ASA 75 mg OD v ASA 75 mg BID v ASA 160 mg OD
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 ANOVA
    Confidence interval

    Primary: Platelet counts at postop

    		 Close Top of page
    End point title
    		 Platelet counts at postop
    End point description
    End point type
    Primary
    End point timeframe
    Platelet counts at discharge (postop) and 1 and 3 months after the operation in patients receiving three dosages of ASA (75 mg OD, 75 mg BID and 160 OD) after discharge.
    End point values
    		 ASA 75 mg OD ASA 75 mg BID ASA 160 mg OD
    Number of subjects analysed
    11
    14
    17
    Units: 10(9)/L
    arithmetic mean (full range (min-max))
        Postop
    237 (165 to 321)
    210 (147 to 279)
    217 (130 to 348)
        1 month
    314 (233 to 394)
    246 (180 to 338)
    310 (197 to 461)
        3 months
    256 (157 to 362)
    212 (156 to 264)
    238 (164 to 301)
    Statistical analysis title
    		 Difference Platelet counts
    Statistical analysis description
    Differences in platelet counts for within-group differences, compared to preoperative baseline, at discharge (postop) 1- and 3-months postop.
    Comparison groups
    ASA 75 mg OD v ASA 75 mg BID v ASA 160 mg OD
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 ANOVA
    Confidence interval

    Primary: Mean platelet volume at postop

    		 Close Top of page
    End point title
    		 Mean platelet volume at postop
    End point description
    End point type
    Primary
    End point timeframe
    Mean platelet volume at discharge (postop) and 1 and 3 months after the operation in patients receiving three dosages of ASA (75 mg OD, 75 mg BID and 160 OD) after discharge.
    End point values
    		 ASA 75 mg OD ASA 75 mg BID ASA 160 mg OD
    Number of subjects analysed
    11
    14
    17
    Units: fL
    arithmetic mean (full range (min-max))
        Postop
    8 (6.6 to 9.0)
    8 (6.8 to 8.6)
    8 (6.5 to 9.0)
        1 month
    8 (6.7 to 9.2)
    8 (6.6 to 8.5)
    8 (6.2 to 8.8)
        3 month
    8 (6.7 to 9.7)
    8 (6.8 to 8.8)
    8 (6.5 to 9.0)
    Statistical analysis title
    		 Difference Mean platelet volume
    Statistical analysis description
    Differences in mean platelet volumen for within-group differences, compared to preoperative baseline, at discharge (postop) 1- and 3-months postop.
    Comparison groups
    ASA 75 mg OD v ASA 75 mg BID v ASA 160 mg OD
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 > 0.05
    Method
    		 ANOVA
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Up to study completion at 3 months postop.
    Adverse event reporting additional description
    Systematic collection of adverse events at the hospital, no special dictionary was used.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 See AE-description
    Dictionary version
    n/a
    Reporting groups
    Reporting group title
    ASA 75 mg OD
    Reporting group description
    		 Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to ASA 75 mg OD up to three months after the operation.

    Reporting group title
    ASA 75 mg BID
    Reporting group description
    		 Patients were treated with ASA 75 mg OD before the CABG surgery, and randomized to 75 mg twice daily (BID) up to three months after the operation.

    Reporting group title
    ASA 160 mg OD
    Reporting group description
    		 Patients were treated with ASA 75 mg once daily (OD) before the CABG surgery, and randomized to 160 mg OD up to three months after the operation.

    Serious adverse events
    		 ASA 75 mg OD ASA 75 mg BID ASA 160 mg OD
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 11 (0.00%)
    0 / 14 (0.00%)
    0 / 17 (0.00%)
         number of deaths (all causes)
    0
    0
    1
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 ASA 75 mg OD ASA 75 mg BID ASA 160 mg OD
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    2 / 11 (18.18%)
    4 / 14 (28.57%)
    4 / 17 (23.53%)
    Blood and lymphatic system disorders
    slight nose bleed, mouth bleeding associated with tooth brushing or bruises
    Additional description: One patient with insulin-treated diabetes mellitus and advanced three-vessel disease treated with ASA 160 mg once daily died suddenly two months after the operation, but the death was not associated with the treatment/study.
         subjects affected / exposed
    2 / 11 (18.18%)
    4 / 14 (28.57%)
    4 / 17 (23.53%)
         occurrences all number
    2
    4
    4

    More information

    		 Close Top of page

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

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Therewas un unfortunate high dropout of initially included patients, we encountered considerable difficulties in obtaining accurate blood samples on all four occasions during the 3m follow-up in several patients.

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/27907814
    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-Wed Apr 24 21:11:36 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA