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

NCT02206815 | Completed Phase 4 DMC

• 1 other identifier: ISSBRIL0256
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Atrial Fibrillation; Coronary Artery Disease

Outcome Measures

Primary Outcomes (1)

• Overall bleeding events

  18 months

Secondary Outcomes (1)

• Major bleeding events

  18 months

Study Arms (2)

Ticagrelor+Warfarin

ACTIVE COMPARATOR

Ticagrelor:Plain, round, yellow, film-coated tablet, 90mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg

Drug: Ticagrelor+Warfarin

Clopidogrel+Aspirin+Warfarin

ACTIVE COMPARATOR

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

Interventions

Ticagrelor+Warfarin DRUG

Ticagrelor 90mg/bid + Warfarin (maintain INR 2.0-2.5)

Also known as: Double antithrombotic therapy

Ticagrelor+Warfarin

Clopidogrel+Aspirin+Warfarin DRUG

Clopidogrel 75mg/day + Aspirin 100mg/day + Warfarin(maintain INR 2.0-2.5)

Also known as: Triple antithrombotic therapy

Clopidogrel+Aspirin+Warfarin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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).

Sponsors & Collaborators

• Genshan Ma: lead
• Zhongda Hospital: collaborator

Study Sites (3)

Zhongda Hospital

Nanjing, Jiangsu, 210009, China

Location

The forth hospital of Xuzhou

Xuzhou, Jiangsu, 0516, China

Location

Jiangbin hospital

Zhenjiang, Jiangsu, 0511, China

Location

Related Publications (2)

• 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.

  PMID: 34712714 DERIVED

• 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.

  PMID: 25513965 DERIVED

MeSH Terms

Conditions

Atrial Fibrillation; Coronary Artery Disease

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Genshan Ma, PhD.

  Southeast University

  STUDY DIRECTOR

• Yu Wang, MD.

  Southeast University

  PRINCIPAL INVESTIGATOR

• Yuyu Yao, Ph.D

  Southeast University

  PRINCIPAL INVESTIGATOR

• Wenbin Lu, MD.

  Southeast University

  PRINCIPAL INVESTIGATOR

• Cong Fu, MD.

  Southeast University

  PRINCIPAL INVESTIGATOR

• LIjuan Chen, PhD.

  Southeast University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Genshan Ma, MD, PhD, Director of Cardiovascular Institute, Southeast University

Study Record Dates

• First Submitted: July 30, 2014
• First Posted: August 1, 2014
• Study Start: September 19, 2014
• Primary Completion: February 20, 2019
• Study Completion: February 20, 2019
• Last Updated: April 14, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)