Platelet Sub-study of the TWILIGHT Trial

TWILIGHT study is a multicenter RCT comparing treatment with ticagrelor alone versus ticagrelor plus aspirin in high-risk patients after PCI. All patients will receive DAPT (ticagrelor plus aspirin) for the initial 3 months post-PCI and then be randomized to either Ticagrelor alone OR Ticagrelor plus Aspirin DAPT.

To investigate the pharmacodynamic effects of the two treatments in this trial, a 'Platelet Sub-study' will be conducted only at the Mount Sinai Medical Center. The sub-study will recruit randomized patients from the TWILIGHT Trial at Mount Sinai and conduct specialized blood tests at randomization and one month thereafter. The aim of the Platelet Sub-study is to compare the antithrombotic effects of Ticagrelor alone versus Ticagrelor plus Aspirin using an ex vivo model of thrombosis (Badimon Chamber).

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Coronary Artery Disease
• Intervention / Treatment: Drug: Ticagrelor; Drug: ASA

Detailed Description

The present study will enroll a cohort of randomized patients from the TWILIGHT trial at the Mount Sinai Medical Center. These subjects will undergo blood sampling and measurement of thrombotic indices at the time of randomization and 1-6 months thereafter.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Randomized subjects from the TWILIGHT trial treated at Mount Sinai Medical Center

Description

Inclusion Criteria:

Patients enrolled in the TWILIGHT trial:

Clinical Inclusion Criteria (must meet at least one):

• Adult patients ≥ 65 years of age
• Troponin (+) acute coronary syndrome
• Female gender
• Established vascular disease defined as previous MI, documented PAD or CAD/PAD revascularization
• Diabetes mellitus treated with medications (oral hypoglycemic, subcutaneous injection of insulin)
• Chronic kidney disease defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or creatinine clearance (CrCl) < 60 ml/min

Angiographic Inclusion Criteria (must meet at least one):

• Multivessel coronary artery disease
• Target lesion requiring total stent length >30 mm
• Thrombotic target lesion(s)
• Bifurcation lesions with Medina X,1,1 classification requiring at least 2 stents
• Left main (≥50%) or proximal LAD (≥70%) lesion
• Calcified target lesion(s) requiring atherectomy

Exclusion Criteria:

Patients not eligible to participate in the TWILIGHT trial:

• Under 18 years of age
• Contraindication to aspirin
• Contraindication to ticagrelor
• Planned surgery within 90 days
• Planned coronary revascularization (surgical or percutaneous) within 90 days
• Need for chronic oral anticoagulation
• Prior stroke
• Dialysis-dependent renal failure
• Active bleeding or extreme-risk for major bleeding (e.g. active peptic ulcer disease, gastrointestinal pathology with a raised risk for bleeding, malignancies with a raised risk for bleeding)
• Emergent or salvage PCI or STEMI presentation.
• Liver cirrhosis
• Life expectancy < 1 year
• Unable or unwilling to provide informed consent
• Women of child bearing potential (as determined by hospital standard of care)
• Fibrinolytic therapy within 24 hours of index PCI
• Concomitant therapy with a strong cytochrome P-450 3A inhibitor or inducer
• Platelet count < 100,000 mm3
• Requiring ongoing treatment with aspirin > 325 mg daily.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ticagrelor; Ticagrelor 90mg tablet bid for 12 months	Drug: Ticagrelor; 90mg tablet bid for 12 months
Ticagrelor + ASA; Ticagrelor 90mg tablet bid for 12 months and enteric coated aspirin 81mg-100mg daily p.o. for 12 months	Drug: Ticagrelor; 90mg tablet bid for 12 months; Drug: ASA; enteric coated aspirin 81mg-100mg daily p.o. for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thrombus size (Badimon Chamber)	Thrombus area measured 1-6 months after randomization	1-6 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet aggregation	Platelet aggregation assessed using Multiplate Analyzer 1-6 months after randomization	1-6 months after randomization

Collaborators and Investigators

• Sponsor: Juan Badimon
• Investigators: Principal Investigator: Juan Badimon, PhD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• Baber U, Zafar MU, Dangas G, Escolar G, Angiolillo DJ, Sharma SK, Kini AS, Sartori S, Joyce L, Vogel B, Farhan S, Gurbel P, Gibson CM, Fuster V, Mehran R, Badimon JJ. Ticagrelor With or Without Aspirin After PCI: The TWILIGHT Platelet Substudy. J Am Coll Cardiol. 2020 Feb 18;75(6):578-586. doi: 10.1016/j.jacc.2019.11.056.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2015
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: June 26, 2019
• First Submitted That Met QC Criteria: June 26, 2019
• First Posted (Actual): June 28, 2019

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 24, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Thrombosis; Platelets; Platelet Aggregation; Blood Thrombogenicity
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Infarction; Infarction; 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
• Other Study ID Numbers: GCO 15-0769

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