Safety of Ticagrelor+ Warfarinin Comparison With Clopidogrel+Aspirin+Warfarin

Study Overview
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Brief Summary
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The aim of this study was to assess safety of antithrombotic drug ticagrelor plus oral anticoagulation adopted in persistent or permanent AF(Atrial fibrillation) patients（CHA2DS2VASc≥2） after PCI-S with specially regard to the occurrence of major bleeding complications. We hypothesized that baseline characteristics (ie age, anemia, previous major bleeding) and type of antithrombotic regimen could influence any bleeding events and the time of bleeding occurrence. We will test this hypothesis by comparing those AF patients who subsequently received double antithrombotic therapy (Ticagrelor + Warfarin) vs. triple antithrombotic therapy (Clopidogrel + Aspirin + Warfarin) after undergoing PCI-S.

Detailed Description
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Currently, the optimal antithrombotic treatment of AF patients with indication for long-term oral anticoagulation undergoing PCI-S is unknown. The randomized trials to assess the best antithrombotic regimen in this setting and the management of this population are challenging. It poses imperative demands for future prospective randomized studies to define the optimal antithrombotic regimen in patients requiring chronic anticoagulation undergoing coronary stenting. Additionally, the vast majority of current clinical studies about antithrombotic therapy for atrial fibrillation together with PCI were retrospectively analysis to date ,whereas the prospective studies are rare and urgently needed

Official Title
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Safety of Ticagrelor Plus Warfarin Versus Clopidogrel+Aspirin+Warfarin in Patients With Persistent or Permanent Atrial Fibrillation and Undergoing PCI-S: A Randomized, Open, Controlled, Parallel Group, Multi-center Trial

Conditions
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Atrial Fibrillation, Coronary Artery Disease

Intervention / Treatment
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* Drug: Ticagrelor+Warfarin
* Drug: Clopidogrel+Aspirin+Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteered to participate in this study and signed an informed consent form; Men or non-pregnant women ≥ 18 and ≤75 years of age; Lesion is located in a coronary artery and the need for coronary drug-eluting stent implantation; Patients with persistent or permanent atrial fibrillation; Score of CHA2DS2VASc≥2. Exclusion Criteria: Severe liver and kidney diseases (GFR<60 ml/min/1.73m2 or CTP≥6 score); Moderate to severe hypertension (after standard antihypertensive therapy, blood pressure higher than 160/100mmHg); Patients with hemodynamic or electrical instability (including shock); Coagulation disorders associated with significant bleeding tendency (eg, hypersensitivity, active bleeding, moderate or severe liver disease, history of previous intracranial bleed, GI bleed within the past 6 months, major surgery within 30 days); Patients with ischemic stroke within one week; Patients with Bronchial asthma, Chronic obstructive pulmonary disease (COPD), and patients with diseases related to dyspnoea; Any contraindication against the use of ticagrelor and other study drugs; Platelet count less than 100 x 109/L; Haemoglobin (Hb) level less than 100 g/L; Researchers involved in the study and / or immediate family members; Participation in another investigation drug or device study in the past 30 days before enrollment; Involvement in the planning and conduct of the study (applies to staffs at study sites); Suffering from other serious disorders and the life expectancy less than half year; Increased risk of bradycardic events (e.g. no pacemaker and known sick sinus syndrome, second degree A-V block, third degree A-V block or previous documented syncope suspected to be due to bradycardia). The Sponsor will review the Holter data in this study to assess the need to continue with this exclusion; Pregnancy or lactation or females of child-bearing potential with the plan of pregnancy in one year; Concomitant oral or intravenous therapy (see examples below) with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic indices, or strong CYP3A inducers which cannot be stopped for the course of the study （Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir; Substrates with narrow therapeutic index: cyclosporine, quinidine；Strong inducers: rifampin/rifampicin, phenytoin, carbamazepine).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ticagrelor+Warfarin<br>Ticagrelor:Plain, round, yellow, film-coated tablet, 90mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg | Drug: Ticagrelor+Warfarin<br>* Ticagrelor 90mg/bid + Warfarin (maintain INR 2.0-2.5)<br>* Other names: Double antithrombotic therapy;|
| Active Comparator: Clopidogrel+Aspirin+Warfarin<br>Clopidogrel:Light red bisulfate tablets, containing one 75mg; Aspirin:Plain, round, white, film-coated tablet, 100mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg | Drug: Clopidogrel+Aspirin+Warfarin<br>* Clopidogrel 75mg/day + Aspirin 100mg/day + Warfarin(maintain INR 2.0-2.5)<br>* Other names: Triple antithrombotic therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall bleeding events |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major bleeding events |  | 18 months |