Dual Antithrombotic Therapy With Dabigatran and Ticagrelor in Patients With ACS and Non-valvular AF Undergoing PCI

Prior treatment

• Gastrointestinal bleeding within 1 month prior to screening unless, in the opinion of the Investigator, the cause has been permanently eliminated (e.g., by surgery);
• Stroke within 1 month prior to screening;
• Major surgery within 1 month prior to screening;
• Malignancy or radiation therapy within 6 months prior to screening unless, in the opinion of the Investigator, the estimated life expectancy is greater than 36 months;
• Past an organ transplant or patient on the waiting list for organ transplant;
• Need for continued treatment with systemic ketoconazole, itraconazole, posaconazole, cyclosporine, tacrolimus, dronedarone, rifampicin, phenytoin, carbamazepine, St. John's Wort or any cytotoxic/myelosuppressive therapy.
• Need for continued treatment with non-steroidal anti-inflammatory drugs (NSAIDs);
• Pre-menopausal women (last menstruation ≤1 year prior to screening) who: sre pregnant or breastfeeding or are not surgically sterile or are of childbearing potential and not practicing two acceptable methods of birth control, or do not plan to continue practicing an acceptable method of birth control throughout the trial. Acceptable methods of birth control are oral or parenteral (patch, injection, implant) hormonal contraception, which has been used continuously for at least one month prior to the first dose of study medication, intrauterine device or intrauterine system, double-barrier method of contraception (condom and occlusive cap or condom and spermicidal agent), male sterilization and complete sexual abstinence (if acceptable by local authorities). Periodic abstinence is not an acceptable method of contraception.
• Participation in another trial with an investigational drug or device within the past 30 days preceding the screening visit (patients participating in an observational study only will not be excluded);
• Patients who are not willing or able to comply with the protocol requirements or considered unreliable by the Investigator concerning the requirements for follow-up during the study and/or compliance with study drug administration, who have a life expectancy less than the expected duration of the trial due to concomitant disease, or who have any condition which in the opinion of the Investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse).

Other illness

• Mechanical or biological heart valve prosthesis;
• Adverse bleeding or ischaemic event during current hospitalization;
• History of intraocular, spinal, retroperitoneal, or traumatic intra-articular bleeding unless the causative factor has been permanently eliminated or repaired;
• Hemorrhagic disorder or bleeding diathesis (e.g. von Willebrand disease, hemophilia A or B or other hereditary bleeding disorder, history of spontaneous intra-articular bleeding, history of prolonged bleeding after surgery/intervention);
• Known allergy to dabigatran, ticagrelor, clopidogrel, aspirin, or to the excipients used for the tables of the drugs;

Lab values

• Anaemia (haemoglobin \<10 g/dL) or thrombocytopenia (platelet count \<100 x109/L) at screening,
• Severe renal impairment (creatinine clearance \<30mL/min (estimated CrCl calculated by Cockcroft-Gault equation) at screening;
• Active liver disease at screening defined as persistently elevated alanine aminotransferase (ALT) or aspartate transaminase (AST) \>3-fold upper limit of normal (ULN)
• Major bleeding episode (reduction in the hemoglobin level of at least 2 g/dL, transfusion of at least two units of blood, or symptomatic bleeding in a critical area or organ), including life-threatening bleeding episode (symptomatic intracranial bleeding, bleeding with a decrease in the hemoglobin level of at least 5 g/dL or bleeding requiring transfusion of at least 4 units of blood or inotropic agents or necessitating surgery) within 1 month prior to screening;

Other

• PCI with bare-metal stent insertion;
• Unsuccessful PCI (\>30% residual stenosis of the target lesion);
• Cardiogenic shock during current hospitalization;
• Use of fibrinolytic agents within 24 hours of screening;
• Contraindications, in the Investigator's opinion to dabigatran, ticagrelor, clopidogrel, or aspirin;

• Male and female patients aged ≥18 years'
• Patients with new-onset or pre-existing non-valvular AF that have been receiving oral anticoagulant treatment with dabigatran for at least 48 hours or were treatment naïve prior to PCI. AF may be paroxysmal, persistent or permanent, but must not be secondary to a reversible disorder such as MI, pulmonary embolism, recent surgery, pericarditis or thyrotoxicosis unless long-term treatment with an OAC is anticipated.
• Patients presenting with ACS that had undergone a successful PCI with drug-eluting stent (DES) implantation or plain old balloon angioplasty within the previous 120 hours. ACS may be ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), or unstable angina (UA). Successful treatment with PCI is defined as achievement of \<30% residual diameter stenosis of the target lesion assessed by visual inspection or quantitative coronary angiography and no in-hospital major adverse cardiac events (AMI or repeat coronary revascularisation of the target lesion). For ACS patients with ST-segment elevation, persistent ST-segment elevation of at least 0.1 mV in at least two contiguous leads or a new left bundle-branch block should be present. For ACS patients without ST-segment elevation, at least two of the following three criteria should be met: (i) ST-segment changes on electrocardiography, indicating ischemia; (ii) a positive test of a biomarker, indicating myocardial necrosis; or (iii) one of several risk factors (age ≥60 years; previous myocardial infarction or coronary artery bypass grafting; coronary artery disease with stenosis of ≥50% in at least two vessels; previous ischemic stroke, transient ischemic attack, carotid stenosis of at least 50%, or cerebral revascularization; diabetes mellitus; peripheral arterial disease; chronic renal dysfunction, defined as a creatinine clearance of \<60 ml per minute per 1.73 m2 of body surface area).
• The patient must be able to give informed consent in accordance with ICH GCP guidelines and local legislation and/or regulations.