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

• ClinicalTrials.gov Identifier: NCT03620760
• Recruitment Status: Unknown
• First Posted: August 8, 2018
• Last Update Posted: December 24, 2018
• Sponsor: Xiaofan Wu
• Information provided by (Responsible Party): Xiaofan Wu, Beijing Anzhen Hospital

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 (Clinical Trial)
• Estimated 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.
• 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: August 7, 2018
• Estimated Primary Completion Date: December 31, 2020
• Estimated Study Completion Date: December 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 Name: 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 Name: AZD6140; Drug: Aspirin; Aspirin 100 mg once daily dose

Outcome Measures

Primary Outcome Measures :

1. Incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) and major bleeding event [ Time Frame: 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 :

1. Any event from the composite of cardiovascular death, non-fatal myocardial infarction, stent thrombosis, coronary revascularization and stroke [ Time Frame: 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.
2. All cause death [ Time Frame: Randomization up to 24 months ]
   Participants with all cause death. ITT analysis of whole population. Events were adjudicated by an endpoint committee.
3. PLATO-defined any bleeding event [ Time Frame: 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:

1. PLATO-defined any minor bleeding event [ Time Frame: 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.
2. PLATO-defined any minimal bleeding event [ Time Frame: 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.
3. Other adverse events [ Time Frame: 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.
4. Experiment examination [ Time Frame: 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

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

Criteria

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

Contacts and Locations

Contacts

Contact: Xiaofan Wu, MD; 13370103552; drwuxf@163.com

Locations

China, Beijing

Xiaofan Wu; Recruiting

Beijing, Beijing, China, 100029

Contact: Xiaofan Wu, Master

Sponsors and Collaborators

Xiaofan Wu

Investigators

• Study Director: Xiaofan Wu; Beijing Anzhen Hospital

More Information

• Responsible Party: Xiaofan Wu, Chief Physician, Beijing Anzhen Hospital
• ClinicalTrials.gov Identifier: NCT03620760
• Other Study ID Numbers: 2018-2-1064
• First Posted: August 8, 2018
• Last Update Posted: December 24, 2018
• Last Verified: December 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Xiaofan Wu, Beijing Anzhen Hospital:

Unstable Angina; Stent; Ticagrelor; Platelet aggregation; Percutaneous Coronary Intervention; Coronary Artery Disease; Major Adverse Cardiovascular and Cerebrovascular Events; Bleeding Events

Additional relevant MeSH terms:

Angina Pectoris; Angina, Unstable; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Aspirin; Ticagrelor; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents