Prevention of Cardiovascular Events (eg, Death From Heart or Vascular Disease, Heart Attack, or Stroke) in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin

Study Overview
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Brief Summary
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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).

Official Title
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A Randomized, Double-Blind, Placebo Controlled, Parallel Group, Multinational Trial, to Assess the Prevention of Thrombotic Events With Ticagrelor Compared to Placebo on a Background of Acetyl Salicylic Acid (ASA) Therapy in Patients With History of Myocardial Infarction

Conditions
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Myocardial Infarction, Cardiovascular Death, Atherothrombosis, Stroke

Intervention / Treatment
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* Drug: Ticagrelor 90 mg
* Drug: Ticagrelor 60 mg
* Drug: Ticagrelor Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Oral Treatment | Drug: Ticagrelor 90 mg<br>* Oral dose twice a day<br>|
| Experimental: 2<br>Oral Treatment | Drug: Ticagrelor 60 mg<br>* Oral dose twice a day<br>|
| Placebo Comparator: 3<br>Oral Treatment | Drug: Ticagrelor Placebo<br>* Oral dose twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Randomization up to 47 months | 
| 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 | First dosing up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Randomization up to 47 months | 
| 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 | Randomization up to 47 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACS, Heart attack, Heart Disease, Acute coronary syndrome, Cardiovascular Disease