Ticagrelor Versus High-dose Clopidogrel in Patients With High Platelet Reactivity on Clopidogrel After PCI (PL-PLATELET)

Ticagrelor Versus High-dose Clopidogrel in Patients With High Platelet Reactivity on Clopidogrel After Percutaneous Coronary Intervention: The PL-PLATELET Randomized Trial

To determine the safety and efficacy of Ticagrelor versus Clopidogrel for the reduction of adverse cardiovascular outcomes in patients with high platelet reactivity on clopidogrel after successful implantation of coronary drug-eluting stents.

Study Overview

• Status: Withdrawn
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Ticagrelor; Drug: Clopidogrel

Detailed Description

This is a multi-center, randomized, single-blind, investigator-initiated study with a parallel design. Patients with coronary artery disease undergoing percutaneous coronary intervention and presenting high platelet reactivity on clopidogrel as assessed with the PL-11 analyzer (platelet maximum aggregation ratio [MAR%] ≥ 55 %) at 2 hours post-clopidogrel 300mg LD (Day 0), will be randomized after informed consent, in a 1:1 ratio to the following treatment groups:

Group Α: Ticagrelor 180 mg immediate loading (on Day 0) followed by 180mg/day starting from Day 1 until Day 365 (12 months after randomization).

Group Β: Clopidogrel 150mg per day, starting from Day 1 until Day 365 (12 months after randomization).

Platelet reactivity assessment will be performed before randomization (Day 0), and 3-day after randomization (Day 3). Documentation of major adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, revascularization procedure with PCI or CABG) and serious adverse events (bleeding, other adverse events) will be performed until 12 months.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital

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 who agreed to the experimental plan which was permitted by IRB;
• Patients planned to take dual antiplatelet therapy for 12 months.

Exclusion Criteria:

• Severe hepatic dysfunction defined as serum transaminase > 3 times normal limit;
• Renal dysfunction defined as eGFR < 30ml/min/1.73m^2;
• Co-morbidity with an estimated life expectancy of < 50 % at 12 months;
• Scheduled surgery in the next 12 months, which resulted protocol changes;
• Known allergy against study drug or device;
• Use of glycoprotein IIb/IIIa inhibitor during the perioperative period;
• Anticoagulation treatment including warfarin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor; Administration of ticagrelor 180mg/day for 12 months.	Drug: Ticagrelor; Daily administration of ticagrelor 180mg for 12 months; Other Names: BRILINTA
Active Comparator: Clopidogrel; Administration of clopidogrel 150 mg/day for 12 months	Drug: Clopidogrel; Daily administration of clopidogrel 150mg for 12 months; Other Names: Plavix, Talcom

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-Month Freedom From MACE	Major adverse cardiovascular and cerebrovascular events consist of all-cause death, target vessel myocardial infarction, stroke, stent thrombosis.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-Month Freedom From Mortality	All-cause death	12 months
12-Month Freedom From Cardiac death	Cardiac death	12 months
12-Month Freedom From MI	Myocardial infarction	12 months
12-Month Freedom From TLR	Target lesion revascularisation	12 months
12-Month Freedom From TVR	Target vessel revascularisation	12 months
12-Month Freedom From Stent Thrombosis	Stent thrombus was classified as definite, probable, or possible, according to the definitions provided by the Academic Research Consortium (ARC).Regarding timing, ST was defined as early (<30 days), late (30 days to 1 year), or too late (>1 year).	12 months
12-Month Freedom From Stroke	Stroke	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-Month Freedom From BARC type 2 or above bleeding	BARC (Bleeding Academic Research Consortium) type 2 or above bleeding event following the first dose of study medication	12 months
12-Month Freedom From Major or minor bleeding	Major or minor bleeding defined by TIMI (thrombolysis in myocardial infarction) bleeding criteria	12 months

Collaborators and Investigators

• Sponsor: Nanjing First Hospital, Nanjing Medical University
• Investigators: Study Chair: Shao-Liang Chen, MD, Nanjing First Hospital, Nanjing Medical University

Publications and helpful links

General Publications

• Zhang JJ, Gao XF, Ge Z, Tian NL, Liu ZZ, Lin S, Ye F, Chen SL. High platelet reactivity affects the clinical outcomes of patients undergoing percutaneous coronary intervention. BMC Cardiovasc Disord. 2016 Nov 29;16(1):240. doi: 10.1186/s12872-016-0394-0.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2017
• Primary Completion (Anticipated): May 30, 2021
• Study Completion (Anticipated): May 30, 2021

Study Registration Dates

• First Submitted: March 7, 2017
• First Submitted That Met QC Criteria: March 7, 2017
• First Posted (Actual): March 13, 2017

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: August 18, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; 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: NFH20170307

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