Myocardial Infarction, Cardiovascular Death, Atherothrombosis, Stroke
Conditions
Keywords
Heart attack, Heart Disease, Acute coronary syndrome, ACS, Cardiovascular Disease
Brief summary
This study is being carried out to see if a new drug called ticagrelor given twice daily in addition to the ASA therapy decreases the frequency of cardiovascular events (e.g., death from heart disease, heart attack, or stroke).
Interventions
DRUGTicagrelor 90 mg
Oral dose twice a day
DRUGTicagrelor 60 mg
Oral dose twice a day
Oral dose twice a day
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Person who had a heart attack within 1 - 3 years ago and at least one additional risk factor: Age ≥ 65 years old, Diabetes requiring medication, Documented history of 2nd prior MI (\>1 year ago). Angiographic evidence of multivessel CAD, and / or Chronic, non-end stage renal dysfunction. * Females of child-bearing potential must have a negative pregnancy test at enrollment * Persons who are currently taking aspirin between 75 and 150 mg once daily
Exclusion criteria
* Persons who are being treated with agents inhibiting blood clotting if the agent cannot be stopped at study start * Persons who have planned coronary, cerebrovascular, or peripheral arterial Revascularization (invasive surgery) at study start * Persons with known bleeding disorders * Persons who need chronic oral anticoagulant therapy or chronic low-molecular-weight heparin * Persons with a history of ischemic stroke * Persons with a history of intracranial bleeding at any time, a tumor or blood vessel abnormality in the brain and/or spinal cord at any time, a history of surgery involving the brain or spinal cord within the last 5 years, or a history of bleeding from the gastrointestinal tract (eg, esophagus, stomach, colon, rectum) within the last 6 months or a major surgery within the last 30 days. * Persons considered to be at risk of bradycardic events unless already treated with a permanent pacemaker * Persons who have had open heart surgery within the past 5 years, unless the person had a heart attack after the surgery * Persons with known severe liver disease * Persons with kidney failure requiring dialysis * Persons with life expectancy \< 1 year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death), Myocardial Infarction (MI) or Stroke Within 3 Years From Randomization | Randomization up to 47 months | Participants with CV death, MI or Stroke. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent, non-CV death or at the last time point of complete clinical event assessment. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who experienced CV Death, MI or stroke within 3 years from randomization |
| Kaplan-Meier Estimate of the Percentage of Patients Who Experienced a TIMI Major Bleeding Within 3 Years From First Dose of Study Drug Units: Percentage of Patients | First dosing up to 48 months | A Thrombolysis in Myocardial Infarction (TIMI) study group major bleeding is defined as any fatal bleeding (leading directly to death within 7 days), any intrcranial bleeding or any clinically overt signs of haemorrhage associated with a drop in Haemoglobin of \>= 5g/dL. Events were adjudicated by a clinical events committee. Censoring ocurrs at 7 days following last dose of study drug. The Kaplan-Meier estimate reports the percentage of patients who experienced a TIMI Major bleeding within 3 years from first dose of study drug |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death) Within 3 Years From Randomization | Randomization up to 47 months | Participants with CV death. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent, non-CV death or at the last time point of complete clinical event assessment. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who experienced CV Death within 3 years from randomization |
| Kaplan-Meier Estimate of the Percentage of Patients Who Died From Any Cause Within 3 Years From Randomization | Randomization up to 47 months | Participants with death from any cause. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent or the last time point the particapant was known to be alive. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who died from any cause within 3 years from randomization |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czechia, France, Germany, Hungary, Italy, Japan, Netherlands, Norway, Peru, Philippines, Poland, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
The Participant Flow shows patients randomized. This number is different from patients enrolled in the protocol section which includes patients who were enrolled, but not randomized.
Participants by arm
| Arm | Count |
|---|---|
| Ticagrelor 90 mg Ticagrelor 90 mg twice daily (BD) | 7,050 |
| Ticagrelor 60 mg Ticagrelor 60 mg twice daily (BD) | 7,045 |
| Placebo Matching placebo | 7,067 |
| Total | 21,162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 6 | 1 |
| Overall Study | Withdrawal by Subject | 52 | 50 | 52 |
Baseline characteristics
| Characteristic | Ticagrelor 90 mg | Ticagrelor 60 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 8.4 | 65.2 years STANDARD_DEVIATION 8.4 | 65.4 years STANDARD_DEVIATION 8.3 | 65.3 years STANDARD_DEVIATION 8.3 |
| Sex: Female, Male Female | 1682 Participants | 1661 Participants | 1717 Participants | 5060 Participants |
| Sex: Female, Male Male | 5368 Participants | 5384 Participants | 5350 Participants | 16102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 945 / 6,996 | 1,992 / 6,958 | 2,245 / 6,988 |
| serious Total, serious adverse events | 1,757 / 6,996 | 1,853 / 6,958 | 1,918 / 6,988 |
Outcome results
Primary
Kaplan-Meier Estimate of the Percentage of Patients Who Experienced a TIMI Major Bleeding Within 3 Years From First Dose of Study Drug Units: Percentage of Patients
A Thrombolysis in Myocardial Infarction (TIMI) study group major bleeding is defined as any fatal bleeding (leading directly to death within 7 days), any intrcranial bleeding or any clinically overt signs of haemorrhage associated with a drop in Haemoglobin of \>= 5g/dL. Events were adjudicated by a clinical events committee. Censoring ocurrs at 7 days following last dose of study drug. The Kaplan-Meier estimate reports the percentage of patients who experienced a TIMI Major bleeding within 3 years from first dose of study drug
Time frame: First dosing up to 48 months
Population: The safety analysis set defined as all patients who took at least one dose of study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced a TIMI Major Bleeding Within 3 Years From First Dose of Study Drug Units: Percentage of Patients | 2.6 Percentage of Patients |
| Ticagrelor 60 mg | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced a TIMI Major Bleeding Within 3 Years From First Dose of Study Drug Units: Percentage of Patients | 2.3 Percentage of Patients |
| Placebo | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced a TIMI Major Bleeding Within 3 Years From First Dose of Study Drug Units: Percentage of Patients | 1.1 Percentage of Patients |
p-value: <0.000195% CI: [1.96, 3.7]Regression, Cox
p-value: <0.000195% CI: [1.68, 3.21]Regression, Cox
Primary
Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death), Myocardial Infarction (MI) or Stroke Within 3 Years From Randomization
Participants with CV death, MI or Stroke. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent, non-CV death or at the last time point of complete clinical event assessment. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who experienced CV Death, MI or stroke within 3 years from randomization
Time frame: Randomization up to 47 months
Population: Intention to treat (ITT) population defined as all participants who were randomized to study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death), Myocardial Infarction (MI) or Stroke Within 3 Years From Randomization | 7.8 Percentage of Patients |
| Ticagrelor 60 mg | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death), Myocardial Infarction (MI) or Stroke Within 3 Years From Randomization | 7.8 Percentage of Patients |
| Placebo | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death), Myocardial Infarction (MI) or Stroke Within 3 Years From Randomization | 9.0 Percentage of Patients |
p-value: 0.00895% CI: [0.75, 0.96]Regression, Cox
p-value: 0.004395% CI: [0.74, 0.95]Regression, Cox
Secondary
Kaplan-Meier Estimate of the Percentage of Patients Who Died From Any Cause Within 3 Years From Randomization
Participants with death from any cause. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent or the last time point the particapant was known to be alive. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who died from any cause within 3 years from randomization
Time frame: Randomization up to 47 months
Population: Intention to treat (ITT) population defined as all participants who were randomized to study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg | Kaplan-Meier Estimate of the Percentage of Patients Who Died From Any Cause Within 3 Years From Randomization | 5.1 Percentage of Patients |
| Ticagrelor 60 mg | Kaplan-Meier Estimate of the Percentage of Patients Who Died From Any Cause Within 3 Years From Randomization | 4.7 Percentage of Patients |
| Placebo | Kaplan-Meier Estimate of the Percentage of Patients Who Died From Any Cause Within 3 Years From Randomization | 5.2 Percentage of Patients |
p-value: 0.985195% CI: [0.86, 1.16]Regression, Cox
p-value: 0.13595% CI: [0.76, 1.04]Regression, Cox
Secondary
Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death) Within 3 Years From Randomization
Participants with CV death. If no event, censoring occurs at the earliest of the efficacy cut-off date 14 Sep 2014, withdrawal of consent, non-CV death or at the last time point of complete clinical event assessment. Events were adjudicated by a blinded endpoint committee. The Kaplan-Meier estimate reports the percentage of patients who experienced CV Death within 3 years from randomization
Time frame: Randomization up to 47 months
Population: Intention to treat (ITT) population defined as all participants who were randomized to study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ticagrelor 90 mg | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death) Within 3 Years From Randomization | 2.9 Percentage of Patients |
| Ticagrelor 60 mg | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death) Within 3 Years From Randomization | 2.9 Percentage of Patients |
| Placebo | Kaplan-Meier Estimate of the Percentage of Patients Who Experienced Cardiovascular Death (CV Death) Within 3 Years From Randomization | 3.4 Percentage of Patients |
p-value: 0.154795% CI: [0.71, 1.06]Regression, Cox
p-value: 0.067695% CI: [0.68, 1.01]Regression, Cox