Atrial FibrillationPhase 4NCT02206815
Safety of "Ticagrelor+ Warfarin"in Comparison With "Clopidogrel+Aspirin+Warfarin"
A Phase 4 study testing Ticagrelor+Warfarin and Clopidogrel+Aspirin+Warfarin in people with Atrial Fibrillation and Coronary Artery Disease, run by Genshan Ma at 3 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Atrial Fibrillation, Coronary Artery Disease
- What is being tested?
- Ticagrelor+Warfarin and Clopidogrel+Aspirin+Warfarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 296 participants
- Where
- 3 sitesChina
- Study dates
- 19 Sep 2014to 20 Feb 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 16Show fewer
- 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).
Trial locations and contacts
3 sites in 1 country.
China3 sites
Zhongda Hospital
Nanjing, Jiangsu, 210009
The forth hospital of Xuzhou
Xuzhou, Jiangsu, 0516
Jiangbin hospital
Zhenjiang, Jiangsu, 0511
About this study
Official title: 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.
Read the 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
- Conditions
- Atrial Fibrillation, Coronary Artery Disease
- Being tested
- Ticagrelor+Warfarin, Clopidogrel+Aspirin+Warfarin
- Medical subject headings
- Atrial Fibrillation, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor+WarfarinDrug
Also called Double antithrombotic therapy
Ticagrelor 90mg/bid + Warfarin (maintain INR 2.0-2.5)
Clopidogrel+Aspirin+WarfarinDrug
Also called Triple antithrombotic therapy
Clopidogrel 75mg/day + Aspirin 100mg/day + Warfarin(maintain INR 2.0-2.5)
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor+Warfarin | Active comparator | Ticagrelor:Plain, round, yellow, film-coated tablet, 90mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg Receives: 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 Receives: Drug: Clopidogrel+Aspirin+Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall bleeding events
Measured: 18 months
Secondary outcomes (1)
Major bleeding events
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2014 (estimated)
- Study start19 Sep 2014
- Primary completion20 Feb 2019
- Study completion20 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 296 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genshan Ma
- Sponsor type
- University, hospital or other
- Collaborators
- Zhongda Hospital
- Responsible party
- Sponsor-investigator, Genshan Ma, Southeast University, China
- Investigators
- Genshan Ma, PhD., Study director, Southeast UniversityYu Wang, MD., Principal investigator, Southeast UniversityYuyu Yao, Ph.D, Principal investigator, Southeast UniversityWenbin Lu, MD., Principal investigator, Southeast UniversityCong Fu, MD., Principal investigator, Southeast UniversityLIjuan Chen, PhD., Principal investigator, Southeast University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02206815
- Sponsor's protocol ID
- ISSBRIL0256
- Status last verified
- Apr 2023
- First submitted
- 30 Jul 2014
- Last updated
- 14 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Li Y, Lu W, Wang Y, Chen L, Ma G. Risk factors of bleeding in patients with atrial fibrillation undergoing percutaneous coronary intervention: an analysis from the MANJUSRI study. Front Cardiovasc Med. 2026 May 18;13:1752209. doi: 10.3389/fcvm.2026.1752209. eCollection 2026.
PubMed 42232312Lu 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.
PubMed 34712714Lu 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.
PubMed 25513965
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02206815
- Acronym / sponsor ID
- ISSBRIL0256
- Conditions
- Atrial Fibrillation, Coronary Artery Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 296 participants (actual)
- Lead sponsor
- Genshan MaUniversity, hospital or other
- Collaborators
- Zhongda Hospital
- Study start
- 19 Sep 2014 (actual)
- Primary completion
- 20 Feb 2019 (actual)
- Study completion
- 20 Feb 2019 (actual)
- First posted
- 1 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor+Warfarin | Active comparator | Drug: Ticagrelor+WarfarinTicagrelor:Plain, round, yellow, film-coated tablet, 90mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg |
| Clopidogrel+Aspirin+Warfarin | Active comparator | Drug: Clopidogrel+Aspirin+WarfarinClopidogrel:Light red bisulfate tablets, containing one 75mg; Aspirin:Plain, round, white, film-coated tablet, 100mg; Warfarin:Plain, round, white, film-coated tablet, 2.5mg |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ticagrelor+WarfarinAlso: Double antithrombotic therapyTicagrelor 90mg/bid + Warfarin (maintain INR 2.0-2.5) | Drug | Ticagrelor+Warfarin |
| Clopidogrel+Aspirin+WarfarinAlso: Triple antithrombotic therapyClopidogrel 75mg/day + Aspirin 100mg/day + Warfarin(maintain INR 2.0-2.5) | Drug | Clopidogrel+Aspirin+Warfarin |
Primary outcome
Overall bleeding events
Time frame: 18 months
1 secondary outcome
Major bleeding events
Time frame: 18 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2023.
- Derived from this study: PubMed 42232312Li Y, Lu W, Wang Y, Chen L, Ma G. Risk factors of bleeding in patients with atrial fibrillation undergoing percutaneous coronary intervention: an analysis from the MANJUSRI study. Front Cardiovasc Med. 2026 May 18;13:1752209. doi: 10.3389/fcvm.2026.1752209. eCollection 2026.
- Derived from this study: PubMed 34712714Lu 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.
- Derived from this study: PubMed 25513965Lu 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.
- Individual participant dataSharing planned: No
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Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Genshan Ma, PhD. study director
Southeast University
Yu Wang, MD. principal investigator
Southeast University
Yuyu Yao, Ph.D principal investigator
Southeast University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ticagrelor+Warfarin and Clopidogrel+Aspirin+Warfarin in people with Atrial Fibrillation and Coronary Artery Disease, run by Genshan Ma at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall bleeding events (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02206815, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2023.