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A Study of the Onset and Offset of Antiplatelet Effects Comparing Ticagrelor, Clopidogrel, and Placebo With Aspirin
This study has been completed.
Study NCT00528411   Information provided by AstraZeneca

First Received on September 10, 2007.   Last Updated on January 12, 2012   History of Changes
Results First Received: January 27, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacodynamics Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Coronary Artery Disease
Interventions: Drug: Ticagrelor Tablets
Drug: Clopidogrel (over encapsulated) capsule
Drug: Aspirin Tablets

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Ticagrelor Ticagrelor 180 mg loading dose followed by 90 mg Twice Daily (bd), plus clopidogrel placebo loading and Once Daily (od) maintenance doses
Clopidogrel Clopidogrel 600 mg loading dose followed by 75 mg Twice Daily (od), plus ticagrelor placebo loading and Once Daily (bd) maintenance doses
Placebo Ticagrelor 180 mg placebo loading dose followed by 90 mg Twice Daily (bd), plus clopidogrel placebo loading and Once Daily (od) maintenance doses

Participant Flow:   Overall Study
    Ticagrelor     Clopidogrel     Placebo  
STARTED     57     54     12  
COMPLETED     52     51     11  
NOT COMPLETED     5     3     1  
Adverse Event                 4                 0                 1  
Incorrect Enrolment                 1                 1                 0  
Severe non-compliance to protocol                 0                 1                 0  
Prior commitment medication                 0                 1                 0  



  Baseline Characteristics
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Reporting Groups
  Description
Ticagrelor Ticagrelor 180 mg loading dose followed by 90 mg bd, plus Clopidogrel placebo loading and od maintenance doses
Clopidogrel Clopidogrel 600 mg loading dose followed by 75 mg od, plus ticagrelor placebo loading and bd maintenance doses
Placebo Ticagrelor 180 mg placebo loading dose followed by 90 mg bd, plus clopidogrel placebo loading and od maintenance doses

Baseline Measures
    Ticagrelor     Clopidogrel     Placebo     Total  
Number of Participants  
[units: participants]
 		  57     54     12     123  
Age  
[units: Year]
Mean ± Standard Deviation 		  62.2  ± 9.10     65.4  ± 7.98     63.9  ± 8.32     63.8  ± 8.62  
Gender  
[units: Participants]
 		       
Female     14     14     2     30  
Male     43     40     10     93  



  Outcome Measures
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1.  Primary:   Final Extent Inhibition of Platelet Aggregation (IPA) Induced by 20 µM Adenosine Diphosphate (ADP) at 2 Hours After First Dose   [ Time Frame: At 2 hours after first dose of study drug ]
  Show Outcome Measure 1

2.  Primary:   Slope of Extent IPA Offset Curve 4 to 72 Hours After Last Dose of Study Drug   [ Time Frame: 4 to 72 Hours after last dose of study drug ]
  Show Outcome Measure 2

3.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 0.5 Hours After First Dose   [ Time Frame: 0.5 hours after first dose ]
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4.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 1 Hour After First Dose   [ Time Frame: 1 hour after first dose ]
  Show Outcome Measure 4

5.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 4 Hours After First Dose   [ Time Frame: 4 hours after first dose ]
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6.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 8 Hours After First Dose   [ Time Frame: 8 hours after first dose ]
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7.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 24 Hours After First Dose   [ Time Frame: 24 hours after first dose ]
  Show Outcome Measure 7

8.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 0 Hour Before Last Dose   [ Time Frame: 0 hour before last dose ]
  Show Outcome Measure 8

9.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 2 Hours After Last Dose   [ Time Frame: 2 hours after last dose ]
  Show Outcome Measure 9

10.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 4 Hours After Last Dose   [ Time Frame: 4 hours after last dose ]
  Show Outcome Measure 10

11.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 8 Hours After Last Dose   [ Time Frame: 8 hours after last dose ]
  Show Outcome Measure 11

12.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 24 Hours After Last Dose   [ Time Frame: 24 hours after last dose ]
  Show Outcome Measure 12

13.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 48 Hours After Last Dose   [ Time Frame: 48 hours after last dose ]
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14.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 72 Hours After Last Dose   [ Time Frame: 72 hours after last dose ]
  Show Outcome Measure 14

15.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 120 Hours - Day 5 After Last Dose   [ Time Frame: 120 hours - Day 5 after last dose ]
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16.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 168 Hours - Day 7 After Last Dose   [ Time Frame: 168 hours - Day 7 after last dose ]
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17.  Secondary:   Final Extent IPA Induced by 20 µM ADP at 240 Hours - Day 10 After Last Dose   [ Time Frame: 240 hours - Day 10 after last dose ]
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18.  Secondary:   Cardiopulmonary Parameters at Baseline: Forced Expiratory Volume in 1 Second (FEV1)   [ Time Frame: Baseline ]
  Show Outcome Measure 18

19.  Secondary:   Cardiopulmonary Parameters at Post 6-week Treatment: FEV1   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 19

20.  Secondary:   Cardiopulmonary Parameters at Baseline: Forced Vital Capacity (FVC)   [ Time Frame: Baseline ]
  Show Outcome Measure 20

21.  Secondary:   Cardiopulmonary Parameters at Post 6-week Treatment: FVC   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 21

22.  Secondary:   Cardiopulmonary Parameters at Baseline: Ratio of Forced Expiratory Volume in 1 Second Over Forced Vital Capacity (FEV1/FVC Ratio)   [ Time Frame: Baseline ]
  Show Outcome Measure 22

23.  Secondary:   Cardiopulmonary Parameters at Post 6-week Treatment: FEV1/FVC Ratio   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 23

24.  Secondary:   Cardiopulmonary Parameters at Baseline: Mean Forced Expiratory Flow Between 25% and 75% of the FVC (FEF25-75)   [ Time Frame: Baseline ]
  Show Outcome Measure 24

25.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: FEF25-75   [ Time Frame: 6-week post treatment ]
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26.  Secondary:   Cardiopulmonary Parameters at Baseline: Functional Residual Capacity (FRC)   [ Time Frame: Baseline ]
  Show Outcome Measure 26

27.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: FRC   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 27

28.  Secondary:   Cardiopulmonary Parameters at Baseline: Total Lung Capacity (TLC)   [ Time Frame: Baseline ]
  Show Outcome Measure 28

29.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: TLC   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 29

30.  Secondary:   Cardiopulmonary Parameters at Baseline: Residual Volume (RV)   [ Time Frame: Baseline ]
  Show Outcome Measure 30

31.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: RV   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 31

32.  Secondary:   Cardiopulmonary Parameters at Baseline: Minute Ventilation (VE)   [ Time Frame: Baseline ]
  Show Outcome Measure 32

33.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: VE   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 33

34.  Secondary:   Cardiopulmonary Parameters at Baseline: Respiratory Rate (RR)   [ Time Frame: Baseline ]
  Show Outcome Measure 34

35.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: RR   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 35

36.  Secondary:   Cardiopulmonary Parameters at Baseline: Tidal Volume (VT)   [ Time Frame: Baseline ]
  Show Outcome Measure 36

37.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: VT   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 37

38.  Secondary:   Cardiopulmonary Parameters at Baseline: Single Breath Diffusing Capacity for the Lungs Using Carbon Monoxide (DLCOSB)   [ Time Frame: Baseline ]
  Show Outcome Measure 38

39.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: DLCOSB   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 39

40.  Secondary:   Cardiopulmonary Parameters at Baseline: Ejection Fraction (EF)   [ Time Frame: Baseline ]
  Show Outcome Measure 40

41.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: EF   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 41

42.  Secondary:   Cardiopulmonary Parameters at Baseline: N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)   [ Time Frame: Baseline ]
  Show Outcome Measure 42

43.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: NT-proBNP   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 43

44.  Secondary:   Cardiopulmonary Parameters at Baseline: Blood Oxygen Saturation Measured by Pulse Oximetry (SpO2)   [ Time Frame: Baseline ]
  Show Outcome Measure 44

45.  Secondary:   Cardiopulmonary Parameters Post 6-week Treatment: SpO2   [ Time Frame: 6-week post treatment ]
  Show Outcome Measure 45


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:  
Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: aztrial_results_posting@astrazeneca.com


No publications provided by AstraZeneca

Publications automatically indexed to this study:
Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010 Dec 1;3(6):556-66. Epub 2010 Nov 15.
Storey RF, Bliden KP, Patil SB, Karunakaran A, Ecob R, Butler K, Teng R, Wei C, Tantry US, Gurbel PA; ONSET/OFFSET Investigators. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol. 2010 Jul 13;56(3):185-93.
Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. Epub 2009 Nov 18.


Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00528411     History of Changes
Other Study ID Numbers: D5130C00048
Study First Received: September 10, 2007
Results First Received: January 27, 2011
Last Updated: January 12, 2012
Health Authority: United States: Food and Drug Administration;   United Kingdom: Medicines and Healthcare Products Regulatory Agency





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