Acute Coronary Syndrome
Conditions
Keywords
ACS, Acute coronary syndrome, Heart attack, Unstable angina, Coronary artery disease
Brief summary
Ticagrelor is a new, reversible binding, anti-platelet medication. Anti-platelet medications work to prevent the formation of blood clots. Ticagrelor is being developed as a treatment for patients with acute coronary syndrome (ACS). ACS is a term that is used to describe both heart attacks in progress or the imminent threat of a heart attack. ACS is usually caused by the formation of a blood clot in an artery that partially or totally blocks the blood supply to a portion of the heart muscle. Ticagrelor will be compared with clopidogrel to determine which drug, when either is used in conjunction with aspirin, is better at reducing deaths from vascular causes, future heart attacks and/or strokes in patients with ACS.
Interventions
DRUGTicagrelor
Ticagrelor (AZD6140) 90 mg twice daily dose (BD)
DRUGClopidogrel
Clopidogrel 75 mg once daily dose (ODD)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female 18 years or older who has been hospitalised for chest pain and potential ACS * Females of child-bearing potential must have a negative pregnancy test at enrollment and be willing to use 2 methods of reliable contraception
Exclusion criteria
* Persons with moderate or severe liver disease * Persons who have already been treated with an invasive (angioplasty) procedure for the current episode of ACS * Persons who are being treated with blood clotting agents that cannot be stopped
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Any Event From the Composite of Death From Vascular Causes, Myocardial Infarction (MI), and Stroke | Randomization up to 12 months | Participants with death from vascular causes, MI, or stroke. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. Intention To Treat (ITT) analysis of whole population. Events were adjudicated by an endpoint committee. |
| Participants With Any Major Bleeding Event | First dosing up to 12 months | Participants with major (fatal/life-threatening or other) bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Any Event From the Composite of Death From Vascular Causes, MI (Including Silent), Stroke, Recurrent Ischemia, Transient Ischemic Attack (TIA) and Other Arterial Thrombotic Events. | Randomization up to 12 months | Participants with death from vascular causes, MI, stroke, recurrent ischemia, or other thrombotic events. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT analysis of whole population. Events were adjudicated. |
| Participants With MI Event | Randomization up to 12 months | Participants with MI event. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT (intention to treat) analysis of whole population. Events were adjudicated by an endpoint committee. |
| Participants With Death From Vascular Causes | Randomization up to 12 months | Participants with death from vascular causes. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT (intention to treat) analysis of whole population. Events were adjudicated by an endpoint committee. |
| Participants With Stroke | Randomization up to 12 months | Participants with stroke. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT (intention to treat) analysis of whole population. Events were adjudicated by an endpoint committee. |
| Participants With Death From Any Cause | Randomization up to 12 months | Participants with death from any cause. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT (intention to treat) analysis of whole population. Events were adjudicated by an endpoint committee. |
| Participants With Non-CABG (Coronary Artery Bypass Graft) Related Major Bleeding | First dosing up to 12 months | Participants with non CABG related major (fatal/life-threatening or other) bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee. |
| Participants With Any Event From the Composite of Death From Vascular Causes, MI, and Stroke for the Subgroup of Patients With Intent for Invasive Management at Randomization | Randomization up to 12 months | Participants with death from vascular causes, MI, or stroke. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT analysis of intent for invasive management population. Events were adjudicated by an endpoint committee. |
| Participants With Non-procedural Major Bleeding | First dosing up to 12 months | Participants with non-procedural major bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee. |
| Participants With Coronary Artery Bypass Graft (CABG) Major Bleeding | First dosing up to 12 months | Participants with a major CABG-related bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. All CABG surgeries were submitted for adjudication by an endpoint committee as potential bleeds. |
| Participants With Coronary Artery Bypass Graft (CABG) Major Fatal/Life-threatening Bleeding | First dosing up to 12 months | Number of participants with a major fatal/life-threatening CABG-related bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. All CABG surgeries were submitted for adjudication by an endpoint committee as potential bleeds. |
| Participants With Ventricular Pauses of Greater Than or Equal to 3 Seconds in Patients Monitored by Holter 24-hour ECG Recorders for 1 Week Following Randomization | 1-week period following randomization | Number of participants who were observed to have at least 1 ventricular pause of at least 3 seconds. Population is all patients who were observed over 2 week-long periods. Pauses were flagged algorithmically and confirmed by Thrombolysis in Myocardial Infarction (TIMI) group cardiologists. |
| Participants With Ventricular Pauses of Greater Than or Equal to 3 Seconds in Patients Monitored by Holter 24 Hour ECG Recorders for 1 Week at 1 Month Following Randomization | 1-week period following randomization | Number of participants who were observed to have at least 1 ventricular pause of at least 3 seconds. Population is all patients who were observed over 2 week-long periods. Pauses were flagged algorithmically and confirmed by TIMI cardiologists. |
| Participants With Major or Minor Bleeding | First dosing up to 12 months | Participants with major (fatal/life-threatening or other) or minor bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee. |
| Participants With Any Event From the Composite of All-cause Mortality, MI, and Stroke | Randomization up to 12 months | Participants with death from any cause, MI, or stroke. If no event, censoring occurs at the earliest of patient withdrawal of consent or date of scheduled withdrawal from therapy. ITT analysis of whole population. Events were adjudicated by an endpoint committee. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Finland, France, Georgia, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Israel, Italy, Malaysia, Mexico, Netherlands, Norway, Philippines, Poland, Portugal, Puerto Rico, Romania, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The first participant was enrolled on 11 October 2006 and the last participant completed the study on 27 February 2009. Study participants were randomized from 855 centers in 43 countries.
Pre-assignment details
Participants will already be hospitalized due to their acute condition, and must be enrolled and randomized within 24 hours of the onset of their most recent cardiac ischemic symptoms. Randomization should take place as soon as possible after presentation.
Participants by arm
| Arm | Count |
|---|---|
| TICAGRELOR Ticagrelor 90 mg twice daily dose (BD) | 9,333 |
| CLOPIDOGREL Clopidogrel 75 mg once daily dose (ODD) | 9,291 |
| Total | 18,624 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 7 | 2 |
| Overall Study | Reason unknown | 2 | 4 |
| Overall Study | Withdrawal by Subject | 296 | 249 |
Baseline characteristics
| Characteristic | TICAGRELOR | CLOPIDOGREL | Total |
|---|---|---|---|
| Age Continuous | 62.1 years STANDARD_DEVIATION 11.21 | 62.3 years STANDARD_DEVIATION 11.21 | 62.2 years STANDARD_DEVIATION 22.42 |
| Sex: Female, Male Female | 2655 Participants | 2633 Participants | 5288 Participants |
| Sex: Female, Male Male | 6678 Participants | 6658 Participants | 13336 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2,278 / — | 1,665 / — |
| serious Total, serious adverse events | 2,108 / — | 2,117 / — |
Outcome results
Primary
Participants With Any Event From the Composite of Death From Vascular Causes, Myocardial Infarction (MI), and Stroke
Participants with death from vascular causes, MI, or stroke. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. Intention To Treat (ITT) analysis of whole population. Events were adjudicated by an endpoint committee.
Time frame: Randomization up to 12 months
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Any Event From the Composite of Death From Vascular Causes, Myocardial Infarction (MI), and Stroke | 864 Participants |
| CLOPIDOGREL | Participants With Any Event From the Composite of Death From Vascular Causes, Myocardial Infarction (MI), and Stroke | 1014 Participants |
Primary
Participants With Any Major Bleeding Event
Participants with major (fatal/life-threatening or other) bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee.
Time frame: First dosing up to 12 months
Population: The population was the safety analysis set, which included all randomized patients who took at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Any Major Bleeding Event | 961 Participants |
| CLOPIDOGREL | Participants With Any Major Bleeding Event | 929 Participants |
Secondary
Participants With Any Event From the Composite of All-cause Mortality, MI, and Stroke
Participants with death from any cause, MI, or stroke. If no event, censoring occurs at the earliest of patient withdrawal of consent or date of scheduled withdrawal from therapy. ITT analysis of whole population. Events were adjudicated by an endpoint committee.
Time frame: Randomization up to 12 months
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Any Event From the Composite of All-cause Mortality, MI, and Stroke | 901 Participants |
| CLOPIDOGREL | Participants With Any Event From the Composite of All-cause Mortality, MI, and Stroke | 1065 Participants |
Secondary
Participants With Any Event From the Composite of Death From Vascular Causes, MI, and Stroke for the Subgroup of Patients With Intent for Invasive Management at Randomization
Participants with death from vascular causes, MI, or stroke. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT analysis of intent for invasive management population. Events were adjudicated by an endpoint committee.
Time frame: Randomization up to 12 months
Population: The subgroup of patients with intent for invasive management at randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Any Event From the Composite of Death From Vascular Causes, MI, and Stroke for the Subgroup of Patients With Intent for Invasive Management at Randomization | 569 Participants |
| CLOPIDOGREL | Participants With Any Event From the Composite of Death From Vascular Causes, MI, and Stroke for the Subgroup of Patients With Intent for Invasive Management at Randomization | 668 Participants |
Secondary
Participants With Any Event From the Composite of Death From Vascular Causes, MI (Including Silent), Stroke, Recurrent Ischemia, Transient Ischemic Attack (TIA) and Other Arterial Thrombotic Events.
Participants with death from vascular causes, MI, stroke, recurrent ischemia, or other thrombotic events. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT analysis of whole population. Events were adjudicated.
Time frame: Randomization up to 12 months
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Any Event From the Composite of Death From Vascular Causes, MI (Including Silent), Stroke, Recurrent Ischemia, Transient Ischemic Attack (TIA) and Other Arterial Thrombotic Events. | 1290 Participants |
| CLOPIDOGREL | Participants With Any Event From the Composite of Death From Vascular Causes, MI (Including Silent), Stroke, Recurrent Ischemia, Transient Ischemic Attack (TIA) and Other Arterial Thrombotic Events. | 1456 Participants |
Secondary
Participants With Coronary Artery Bypass Graft (CABG) Major Bleeding
Participants with a major CABG-related bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. All CABG surgeries were submitted for adjudication by an endpoint committee as potential bleeds.
Time frame: First dosing up to 12 months
Population: Population is all patients who underwent CABG surgery within 7 days of last dose of active study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Coronary Artery Bypass Graft (CABG) Major Bleeding | 619 Participants |
| CLOPIDOGREL | Participants With Coronary Artery Bypass Graft (CABG) Major Bleeding | 654 Participants |
Secondary
Participants With Coronary Artery Bypass Graft (CABG) Major Fatal/Life-threatening Bleeding
Number of participants with a major fatal/life-threatening CABG-related bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. All CABG surgeries were submitted for adjudication by an endpoint committee as potential bleeds.
Time frame: First dosing up to 12 months
Population: Population is all patients who underwent CABG surgery within 7 days of last dose of active study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Coronary Artery Bypass Graft (CABG) Major Fatal/Life-threatening Bleeding | 329 Participants |
| CLOPIDOGREL | Participants With Coronary Artery Bypass Graft (CABG) Major Fatal/Life-threatening Bleeding | 341 Participants |
Secondary
Participants With Death From Any Cause
Participants with death from any cause. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT (intention to treat) analysis of whole population. Events were adjudicated by an endpoint committee.
Time frame: Randomization up to 12 months
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Death From Any Cause | 399 Participants |
| CLOPIDOGREL | Participants With Death From Any Cause | 506 Participants |
Secondary
Participants With Death From Vascular Causes
Participants with death from vascular causes. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT (intention to treat) analysis of whole population. Events were adjudicated by an endpoint committee.
Time frame: Randomization up to 12 months
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Death From Vascular Causes | 353 Participants |
| CLOPIDOGREL | Participants With Death From Vascular Causes | 442 Participants |
Secondary
Participants With Major or Minor Bleeding
Participants with major (fatal/life-threatening or other) or minor bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee.
Time frame: First dosing up to 12 months
Population: The population was the safety analysis set, which included all randomized patients who took at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Major or Minor Bleeding | 1339 Participants |
| CLOPIDOGREL | Participants With Major or Minor Bleeding | 1215 Participants |
Secondary
Participants With MI Event
Participants with MI event. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT (intention to treat) analysis of whole population. Events were adjudicated by an endpoint committee.
Time frame: Randomization up to 12 months
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With MI Event | 504 Participants |
| CLOPIDOGREL | Participants With MI Event | 593 Participants |
Secondary
Participants With Non-CABG (Coronary Artery Bypass Graft) Related Major Bleeding
Participants with non CABG related major (fatal/life-threatening or other) bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee.
Time frame: First dosing up to 12 months
Population: The population was the safety analysis set, which included all randomized patients who took at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Non-CABG (Coronary Artery Bypass Graft) Related Major Bleeding | 362 Participants |
| CLOPIDOGREL | Participants With Non-CABG (Coronary Artery Bypass Graft) Related Major Bleeding | 306 Participants |
Secondary
Participants With Non-procedural Major Bleeding
Participants with non-procedural major bleed by a study protocol scale based on need for treatment, number of transfusions, hemoglobin decrease, and other factors. Events were adjudicated by an endpoint committee.
Time frame: First dosing up to 12 months
Population: The population was the safety analysis set, which included all randomized patients who took at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Non-procedural Major Bleeding | 235 Participants |
| CLOPIDOGREL | Participants With Non-procedural Major Bleeding | 180 Participants |
Secondary
Participants With Stroke
Participants with stroke. If no event, censoring occurs at the earliest of patient withdrawal consent or date of scheduled withdrawal from therapy. ITT (intention to treat) analysis of whole population. Events were adjudicated by an endpoint committee.
Time frame: Randomization up to 12 months
Population: The population was the full analysis set, which included all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Stroke | 125 Participants |
| CLOPIDOGREL | Participants With Stroke | 106 Participants |
Secondary
Participants With Ventricular Pauses of Greater Than or Equal to 3 Seconds in Patients Monitored by Holter 24 Hour ECG Recorders for 1 Week at 1 Month Following Randomization
Number of participants who were observed to have at least 1 ventricular pause of at least 3 seconds. Population is all patients who were observed over 2 week-long periods. Pauses were flagged algorithmically and confirmed by TIMI cardiologists.
Time frame: 1-week period following randomization
Population: Patients who were monitored for one week following randomization (and for one week one month later).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Ventricular Pauses of Greater Than or Equal to 3 Seconds in Patients Monitored by Holter 24 Hour ECG Recorders for 1 Week at 1 Month Following Randomization | 21 Participants |
| CLOPIDOGREL | Participants With Ventricular Pauses of Greater Than or Equal to 3 Seconds in Patients Monitored by Holter 24 Hour ECG Recorders for 1 Week at 1 Month Following Randomization | 16 Participants |
Secondary
Participants With Ventricular Pauses of Greater Than or Equal to 3 Seconds in Patients Monitored by Holter 24-hour ECG Recorders for 1 Week Following Randomization
Number of participants who were observed to have at least 1 ventricular pause of at least 3 seconds. Population is all patients who were observed over 2 week-long periods. Pauses were flagged algorithmically and confirmed by Thrombolysis in Myocardial Infarction (TIMI) group cardiologists.
Time frame: 1-week period following randomization
Population: Participants with Holter data in the week after Randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TICAGRELOR | Participants With Ventricular Pauses of Greater Than or Equal to 3 Seconds in Patients Monitored by Holter 24-hour ECG Recorders for 1 Week Following Randomization | 84 Participants |
| CLOPIDOGREL | Participants With Ventricular Pauses of Greater Than or Equal to 3 Seconds in Patients Monitored by Holter 24-hour ECG Recorders for 1 Week Following Randomization | 51 Participants |