Rapid P2Y12 Receptor Inhibition Attenuates Inflammatory Cell Infiltration in Thrombus Aspirated From the STEMI Patients

Rapid P2Y12 Receptor Inhibition Attenuates Inflammatory Cell Infiltration in Thrombus Aspirated From the Infarct-related Artery in STEMI Patients: A Prospective Randomized Trial of Ticagrelor Versus Clopidogrel

This is a prospective, randomized, parallel design study to investigate that ticagrelor could attenuate inflammatory cell infiltration in thrombus aspirated from ST elevation myocardial infarction (STEMI) patients. The anticipated duration of the study is approximately 9 months, including an anticipated enrolment period of 8 months and follow-up period of 1 month. Patients within 12 hours of symptom onset were randomly assigned in a one-to-one ratio to receive ticagrelor or clopidogrel at time of STEMI diagnosis. The primary endpoint was the extent of inflammatory cell infiltration in thrombus aspirated from STEMI patients, expressed as number of total inflammatory cells per mm2 thrombus area.

Study Overview

• Status: Completed
• Conditions: Inflammation; Thrombosis
• Intervention / Treatment: Drug: Clopidogrel; Drug: ticagrelor

Detailed Description

This is a prospective, randomized, parallel design study to investigate that ticagrelor could attenuate inflammatory cell infiltration in thrombus aspirated from STEMI patients. The anticipated duration of the study is approximately 9 months, including an anticipated enrolment period of 8 months and follow-up period of 1 month. Patients within 12 hours of symptom onset were randomly assigned in a one-to-one ratio to receive ticagrelor or clopidogrel at time of STEMI diagnosis. The primary endpoint was the extent of inflammatory cell infiltration in thrombus aspirated from STEMI patients, expressed as number of total inflammatory cells per mm2 thrombus area.

Screening will be made to select eligible participants before intervention. Patients with documented STEMI and within 12 hours of symptom onset will be enrolled from the study site. For patients post percutaneous coronary intervention (PCI), they must be on dual-antiplatelet therapy for at least 12 months to be eligible for the study.

After the enrollment period, patients were randomly assigned in a one-to-one ratio to receive ticagrelor (180 mg loading dose) or clopidogrel (600 mg loading dose) at time of STEMI diagnosis. In addition to randomized study medication all patients should receive concomitant Ace Salicylic Acid (ASA) 100 mg daily during the treatment period according to local practice, unless they are allergic or intolerant. For those not previously given aspirin, a loading dose of 300 mg was preferred. At the end of the study, data will be collected and analyzed.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of informed consent prior to any study specific procedures
• Males and non-pregnant females > 18 and < 79 years of age.
• Symptoms consistent with STEMI lasting > 30 min.
• Arrival at the hospital within 12 h of the onset of chest pain.
• Intention to perform PCI

Exclusion Criteria:

• On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel, ticagrelor) in past 30 days.
• Known allergies to aspirin or ticagrelor or clopidogrel.
• On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).
• Treatment with IIb/IIIa glycoprotein inhibitors in the last 7 days.
• Known pregnancy, breast-feeding, or intend to become pregnant during the study period.
• Active pathological bleeding
• History of prior intracranial bleeding.
• Renal dysfunction (serum creatinine levels ≥ 2.0 mg/dL).
• Severe, non-catheter-related coronary artery spasm.
• New York Heart Association (NYHA) class III or IV heart failure or known left ventricular ejection fraction < 30%.
• Known severe hepatic dysfunction.
• Hemodynamic or electrical instability (including shock).
• Concomitant inflammatory diseases, malignant tumours, anaemia or thrombocytopenia.

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: ticagrelor; Ticagrelor, 180 mg, oral administration. followed by 90 mg bid	Drug: ticagrelor
Active Comparator: Clopidogrel; Clopidogrel 600 mg loading dose taken orally, followed by 75 mg qd.	Drug: Clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of total inflammatory cells per mm2 thrombus area.	To evaluate the efficacy of ticagrelor compared to clopidogrel for the attenuation of inflammatory cell infiltration in thrombus aspirated from STEMI patients.	Thrombus will be got from aspiration in culprit lesions during primary PCI.It will be fixed immediately and tested in 48 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracoronary thrombus size		Thrombus will be got from aspiration in culprit lesions during primary PCI.It will be fixed immediately and tested in 48 hours.
Number of neutrophils per mm2 thrombus area		Thrombus will be got from aspiration in culprit lesions during primary PCI.It will be fixed immediately and tested in 48 hours.
Number of macrophages per mm2 thrombus area		Thrombus will be got from aspiration in culprit lesions during primary PCI.It will be fixed immediately and tested in 48 hours.
Number of Myeloperoxidase-positive cells per mm2 thrombus area		Thrombus will be got from aspiration in culprit lesions during primary PCI.It will be fixed immediately and tested in 48 hours.
Serum high-sensitivity C-reactive protein level	A total of three times	after randomization and before loading dose P2Y12 receptor inhibitor,5-7 days after PCI,1 month ± 5 days.
Plasma concentration of ticagrelor		At 90 min, 2h, 8h, 12h and 24h after received loading dose P2Y12 receptor inhibitor.
Rate of Thrombolysis In Myocardial Infarction (TIMI) major bleeding		Follow up: 1 month ± 5 days.

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Harbin Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: November 23, 2015
• First Submitted That Met QC Criteria: December 20, 2015
• First Posted (Estimate): December 24, 2015

Study Record Updates

• Last Update Posted (Actual): August 23, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Inflammation; Thrombosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: ESR-14-10167