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

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

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.

Study Overview

• Status: Unknown
• Conditions: Unstable Angina Pectoris; Coronary Stent Implantation
• Intervention / Treatment: Drug: Ticagrelor 45 mg; Drug: Aspirin; Drug: Ticagrelor 90 mg

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 Type: Interventional
• Enrollment (Anticipated): 2036
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Xiaofan Wu, MD; Phone Number: 13370103552; Email: drwuxf@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100029
      • Recruiting
      • Xiaofan Wu
      • Contact: Xiaofan Wu, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
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: Aspirin; Aspirin 100 mg once daily dose; Drug: Ticagrelor 90 mg; Ticagrelor (AZD6140) 90 mg twice daily dose; Other Names: AZD6140

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) and major bleeding event	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.	Randomization up to 24 months

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PLATO-defined any minor bleeding event	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.	Randomization up to 24 months
PLATO-defined any minimal bleeding event	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.	Randomization up to 24 months
Other adverse events	To compare two intensities of ticagrelor therapy on other adverse events including dyspnea or bradyarrhythmia. Events were adjudicated by an endpoint committee.	Randomization up to 24 months
Experiment examination	To compare two intensities of ticagrelor therapy on increase of serum uric acid or creatinine. Events were adjudicated by an endpoint committee.	Randomization up to 24 months

Collaborators and Investigators

• Sponsor: Xiaofan Wu
• Investigators: Study Director: Xiaofan Wu, Beijing Anzhen Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 7, 2018
• Primary Completion (Anticipated): December 31, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: August 5, 2018
• First Submitted That Met QC Criteria: August 5, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Ticagrelor; Stent; Coronary Artery Disease; Percutaneous Coronary Intervention; Unstable Angina; Platelet aggregation; Major Adverse Cardiovascular and Cerebrovascular Events; Bleeding Events
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Unstable; 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; Aspirin; Ticagrelor
• Other Study ID Numbers: 2018-2-1064

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No