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
This is an event-driven, randomized, double blind, placebo controlled, parallel group, international multicentre study to assess the prevention of cardiovascular events with ticagrelor given at 2 doses (90 mg bd and 60 mg bd) compared to placebo on a background of ASA in patients with history of MI (1-3 years ago) and additional risk factors for atherothrombosis.
The patients will be followed a minimum of 12 months and up to approximately 38 months. If, however, the number of primary events is not achieved when the last patient has been followed for 12 months, the treatment period may be extended. The expected median duration is 26 months. A study closure plan will be developed to take into account the patient recruitment pattern and number of outcome events experienced (target: 1360). All patients will have a Follow-up Visit approximately 2 weeks after their last dose of study medication.
The study may be terminated early if either a clear beneficial or harmful effect of the study treatment is detected during the Independent Data Monitoring Committee (IDMC) review.
Target patient population; Male and female patients 50 years of age and over with history of MI 1-3 years ago and at least 1 of the following risk factors: age >=65 years, diabetes, a second prior MI, evidence of multivessel coronary artery disease (CAD), or chronic non-end stage renal dysfunction.
ADP receptor blockers (eg, clopidogrel, prasugrel, ticlopidine), dipyridamole, and
cilostazol: Planned concomitant treatment with any of these drugs is not allowed in the study. For situations where a patient already enrolled in the study develops an indication for use of an ADP receptor blocker according to medical guidelines (eg, acute coronary syndrome or percutaneous coronary intervention). If open-label treatment with one of these drugs is considered essential during the study, study medication must be discontinued but may be resumed when open-label treatment is stopped.
This study will be conducted in approximately 1000 investigational centres in approximately 30 countries worldwide. It is expected that approximately 21000 patients will be randomized to study treatment.
Patients will return every 4 months for the first year and then every 6 months after the first year of participation for assessment of events related to the objectives of the study, tolerability and safety. Assessment of treatment compliance and provision of study drug will be done at these visits.
1. Men and women >50 years of age.
2. Documented history of presumed spontaneous MI (excluding known peri-procedural or
definite secondary MI [eg, due to profound hypotension, hypertensive emergency,
tachycardia, or profound anemia]) with their most recent MI occurring 1 to 3 years prior to
randomization and have at least 1 of the following risk factors:
[?] Age >=65 years
[?] Diabetes mellitus requiring medication
[?] Documented history of a second prior presumed spontaneous MI (>1 year ago)
[?] Documented history of angiographic evidence of multivessel coronary artery disease (CAD) (stenoses
>=50% in two major coronary artery territories [ie, left anterior descending,
ramus intermedius, left circumflex, right coronary artery] involving the main
vessel, a major branch, or a bypass graft)1.
[?] Chronic, non-end stage renal dysfunction (creatinine clearance calculated by
Cockcroft Gault equation <60 mL/min)2.
3. Patient currently prescribed and tolerating ASA, and able to be prescribed the protocol
mandated dose of 75 - 150 mg once daily for the duration of the study.
4. Females of child-bearing potential (ie, who are not chemically or surgically sterilized or
who are not post-menopause) must have a negative urine pregnancy test at enrollment (to
be confirmed by blood pregnancy test at the central lab.) Females of child-bearing potential
must be willing to use a medically accepted method of contraception that is considered
reliable in the judgment of the investigator.
5. Written informed consent prior to any study specific procedures.