Safety of "Ticagrelor+ Warfarin"in Comparison With "Clopidogrel+Aspirin+Warfarin"

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Atrial Fibrillation
• Intervention / Treatment: Drug: Ticagrelor+Warfarin; Drug: Clopidogrel+Aspirin+Warfarin

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 296
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital
    • Xuzhou, Jiangsu, China, 0516
      • The forth hospital of Xuzhou
    • Zhenjiang, Jiangsu, China, 0511
      • Jiangbin hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ticagrelor+Warfarin; Ticagrelor:Plain, round, yellow, film-coated tablet, 90mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg	Drug: Ticagrelor+Warfarin; Ticagrelor 90mg/bid + Warfarin (maintain INR 2.0-2.5); Other Names: Double antithrombotic therapy
Active Comparator: Clopidogrel+Aspirin+Warfarin; 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; Clopidogrel 75mg/day + Aspirin 100mg/day + Warfarin(maintain INR 2.0-2.5); Other Names: Triple antithrombotic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall bleeding events	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Major bleeding events	18 months

Collaborators and Investigators

• Sponsor: Genshan Ma
• Collaborators: Zhongda Hospital

Publications and helpful links

General Publications

• Lu W, Wang Y, Chen L, Li Y, Zhang R, Chen Z, Yan J, Yang M, Han B, Wang Z, He S, Chen L, Wu X, Zeng H, Ma L, Shi G, Yin J, Chen J, Ma G. Antithrombotic Therapy With Ticagrelor in Atrial Fibrillation Subjects After Percutaneous Coronary Intervention. Front Cardiovasc Med. 2021 Oct 12;8:745549. doi: 10.3389/fcvm.2021.745549. eCollection 2021.
• Lu W, Chen L, Wang Y, Yao Y, Fu C, Zuo P, Ma G. Rationale and design of MANJUSRI trial: a randomized, open-label, active-controlled multicenter study to evaluate the safety of combined therapy with ticagrelor and warfarin in AF subjects after PCI-eS. Contemp Clin Trials. 2015 Jan;40:166-71. doi: 10.1016/j.cct.2014.12.002. Epub 2014 Dec 13.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2014
• Primary Completion (Actual): February 20, 2019
• Study Completion (Actual): February 20, 2019

Study Registration Dates

• First Submitted: July 30, 2014
• First Submitted That Met QC Criteria: July 30, 2014
• First Posted (Estimate): August 1, 2014

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Arrhythmias, Cardiac; Coronary Disease; Coronary Artery Disease; Atrial Fibrillation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Anticoagulants; Aspirin; Ticagrelor; Clopidogrel; Warfarin
• Other Study ID Numbers: ISSBRIL0256

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO