Efficacy and Safety of Low Dose Ticagrelor in Patients With Unstable Angina Pectoris After Coronary Stent Implantation

Sponsor

Xiaofan Wu (Other)

Overall Status

Unknown status

CT.gov ID

NCT03620760

Collaborator

(none)

2,036

Enrollment

Location

Arms

28.8

Anticipated Duration (Months)

70.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is to evaluate efficacy and safety of low dose of ticagrelor therapy for Chinese unstable angina patients treated with non-urgent coronary stent implantation, to examine whether lower dose ticagrelor (45 mg twice-daily) is not inferior to standard dose (90 mg twice-daily) for the prevention of major adverse cardiovascular and cerebrovascular events, as well as will reduce the incidence of bleeding during long-term treatment.

Condition or Disease	Intervention/Treatment	Phase
Unstable Angina Pectoris Coronary Stent Implantation	Drug: Ticagrelor 90 mg Drug: Ticagrelor 45 mg Drug: Aspirin	Phase 4

Detailed Description

This is a prospective, single center, randomized, parallel-group trial designed to evaluate the efficacy and safety of low dose ticagrelor on a background of aspirin for patients treated with non-urgent coronary stent implantation. 2036 subjects will be enrolled. All patients will receive treatment with aspirin and a P2Y12 inhibitor for 3 months after the index procedure. At 3 months, eligible patients were then randomly assigned in a 1:1 ratio to receive a standard dose ticagrelor 90 mg bid or a lower dose ticagrelor 45 mg bid in addition to aspirin 100mg. The primary efficacy end points are the event rate of the composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, coronary revascularization and stroke at 24 months. The primary safety end point is the incidence of PLATO major bleeding at 24 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2036 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor 90 mg twice daily plus aspirin 100mg once daily or ticagrelor 45 mg twice daily plus aspirin 100mg once daily.Eligible patients were randomly assigned in a 1:1 ratio to receive ticagrelor 90 mg twice daily plus aspirin 100mg once daily or ticagrelor 45 mg twice daily plus aspirin 100mg once daily.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective, Randomised, Open-labeled, Parallel Group Study to Assess the Efficacy and Safety of Low Dose Ticagrelor Compared With Standard Dose Ticagrelor in Patients With Unstable Angina Pectoris After Drug Eluting Stent Implantation

Actual Study Start Date :

Aug 7, 2018

Anticipated Primary Completion Date :

Dec 31, 2020

Anticipated Study Completion Date :

Dec 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lower dose ticagrelor Subjects will be treated with ticagrelor 45 mg twice daily in combination with aspirin 100mg once daily.	Drug: Ticagrelor 45 mg Ticagrelor (AZD6140) 45 mg twice daily dose Other Names: AZD6140 Drug: Aspirin Aspirin 100 mg once daily dose
Active Comparator: Standard dose ticagrelor Subjects will be treated with ticagrelor 90 mg twice daily in combination with aspirin 100mg once daily.	Drug: Ticagrelor 90 mg Ticagrelor (AZD6140) 90 mg twice daily dose Other Names: AZD6140 Drug: Aspirin Aspirin 100 mg once daily dose

Arm

Intervention/Treatment

Experimental: Lower dose ticagrelor

Subjects will be treated with ticagrelor 45 mg twice daily in combination with aspirin 100mg once daily.

Drug: Ticagrelor 45 mg

Ticagrelor (AZD6140) 45 mg twice daily dose

Other Names:

AZD6140

Drug: Aspirin

Aspirin 100 mg once daily dose

Active Comparator: Standard dose ticagrelor

Subjects will be treated with ticagrelor 90 mg twice daily in combination with aspirin 100mg once daily.

Drug: Ticagrelor 90 mg

Ticagrelor (AZD6140) 90 mg twice daily dose

Other Names:

AZD6140

Drug: Aspirin

Aspirin 100 mg once daily dose

Outcome Measures

Primary Outcome Measures

Incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) and major bleeding event [Randomization up to 24 months]
Participants with death from vascular causes, non-fatal myocardial infarction, stent thrombosis, coronary revascularization and stroke. Intention to treat (ITT) analysis of whole population. Events were adjudicated by an endpoint committee. Participants with PLATO major bleeding event including fatal bleeding, intracranial bleeding, intrapericardial bleeding with cardiac tamponade, hypovolemic shock or severe hypotension due to bleeding and requiring pressures or surgery, a decline in the hemoglobin level of 5.0 g per deciliter or more, or the need for transfusion of at least. Events were adjudicated by an endpoint committee.

Secondary Outcome Measures

Any event from the composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, coronary revascularization and stroke [Randomization up to 24 months]
Participants with any event from the composite of cardiovascular death, non-fatal MI, stent thrombosis, coronary revascularization and stroke. ITT analysis of intent for invasive management population. Events were adjudicated by an endpoint committee.
All cause death [Randomization up to 24 months]
Participants with all cause death. ITT analysis of whole population. Events were adjudicated by an endpoint committee.
PLATO-defined any bleeding event [Randomization up to 24 months]
Participants with any other bleeding events (minor bleeding or minimal bleeding) as defined by the PLATO. Events were adjudicated by an endpoint committee.

Other Outcome Measures

PLATO-defined any minor bleeding event [Randomization up to 24 months]
To compare two intensities of ticagrelor therapy on minor bleeding event as any bleeding requiring medical intervention but not meeting the criteria for major bleeding. Events were adjudicated by an endpoint committee.
PLATO-defined any minimal bleeding event [Randomization up to 24 months]
To compare two intensities of ticagrelor therapy on minimal bleeding event as all other bleeding (eg, bruising, bleeding gums, oozing from injection site) not requiring intervention or treatment. Events were adjudicated by an endpoint committee.
Other adverse events [Randomization up to 24 months]
To compare two intensities of ticagrelor therapy on other adverse events including dyspnea or bradyarrhythmia. Events were adjudicated by an endpoint committee.
Experiment examination [Randomization up to 24 months]
To compare two intensities of ticagrelor therapy on increase of serum uric acid or creatinine. Events were adjudicated by an endpoint committee.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients admission for coronary artery disease treatment with non-emergency percutaneous intervention with stent deployment
18 years≤age≤80 years
Patients understands the study requirements and the treatment procedures and provided informed consent before the procedure

Exclusion Criteria:

Allergy or intolerance to ticagrelor or aspirin
Need for oral anticoagulation therapy
Concomitant oral or intravenous therapy with strong inhibitors of Cytochrome P450, family 3, subfamily A (CYP3A), Substrates of CYP3A with narrow therapeutic indices or strong inducers of CYP3A
Active bleeding, previous history of intracranial hemorrhage, gastrointestinal hemorrhage in the past 6 months and major operation within 30 days
High risk of bradyarrhythmias
Severe liver dysfunction and abnormal renal function
Patient is a woman who is pregnant or nursing
Unable or unwilling to give written informed consent