Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention (TWILIGHT)

December 23, 2020 updated by: Roxana Mehran, Icahn School of Medicine at Mount Sinai

The purpose of this study is to compare the use of ticagrelor alone versus ticagrelor and aspirin together. Both ticagrelor and aspirin stop platelets from sticking together and forming a blood clot that could block blood flow to the heart. This study will look to determine the effectiveness and safety of ticagrelor alone, compared to ticagrelor plus aspirin in reducing clinically relevant bleeding and in reducing ischemic adverse events among high-risk patients who have had a percutaneous intervention with at least one drug-eluting stent. A patient is considered high-risk if they meet certain clinical and/or anatomic criteria.

Up to 9000 subjects will be enrolled at the time of their index PCI. Subjects meeting randomization eligibility criteria at 3 months post enrollment will be randomized to either ticagrelor plus aspirin or ticagrelor plus placebo for an additional 12 months. Follow-up clinic visits will be performed at 3 months, 9 months and 15 months post enrollment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, prospective, blinded dual-arm study. Up to 9000 high-risk patients who have undergone successful PCI with at least one locally approved drug eluting stent discharged on DAPT with aspirin and ticagrelor of at least 3 months intended duration from centers still to be determined in the U.S., Canada, Europe and Asia. The primary objective of this study is to determine the impact of antiplatelet monotherapy with ticagrelor alone versus DAPT with ticagrelor plus aspirin for 12 months in reducing clinically relevant bleeding (efficacy) among high-risk patients undergoing PCI who have completed a 3-month course of aspirin plus ticagrelor. The secondary objective of this study is to determine the impact of antiplatelet monotherapy with ticagrelor alone versus DAPT with ticagrelor plus aspirin for 12 months in reducing major ischemic adverse events (safety) among high-risk patients undergoing PCI who have completed a 3-month course of aspirin plus ticagrelor.

Exploratory objectives include assessing the comparative safety and efficacy of the different DAPT regimens for individual components of the primary efficacy and secondary safety objectives.

The primary analysis for TWILIGHT will be performed independently by the London School of Hygiene and Tropical Medicine

Study Type

Interventional

Enrollment (Actual)

9006

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • High-risk patients who have undergone successful PCI with at least one locally approved drug eluting stent discharged on DAPT with aspirin and ticagrelor of at least 3 months intended duration will be eligible for the TWILIGHT study.
  • Enrollment into the study will require meeting at least one clinical inclusion, one angiographic inclusion and none of the exclusion criteria.

Clinical Inclusion Criteria:

  • Adult patients ≥ 65 years of age
  • Female gender
  • Troponin Positive acute coronary syndrome
  • 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:

  • 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:

  • 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)
  • Salvage PCI or STEMI presentation.
  • Liver cirrhosis
  • Life expectancy < 1 year
  • Unable or unwilling to provide informed consent
  • Women of child bearing potential. Defined: a woman is considered potential (WOBCP) following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. a postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
  • 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Aspirin + Ticagrelor
enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
Drug: Aspirin
Other Names:
  • Ecotrin
Drug: ticagrelor
Other Names:
  • Brilinta
  • Brilique
Placebo Comparator: Placebo + Ticagrelor
placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months
Drug: Placebo
Drug: ticagrelor
Other Names:
  • Brilinta
  • Brilique

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With BARC Type 2, 3, or 5
Time Frame: 12 months after randomization
Number of participants with first occurrence of clinically relevant bleeding episode, defined as Bleeding Academic Research Consortium (BARC) Types 2, 3 or 5 bleeding. BARC bleeding types range from 0 (no bleeding) to 5 (fatal bleeding).
12 months after randomization

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Ischemic Episode
Time Frame: 12 months after randomization
Number of participants with first occurrence of confirmed all-cause death, non-fatal myocardial infarction or stroke.
12 months after randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Icahn School of Medicine at Mount Sinai

Collaborators

AstraZeneca

Investigators

  • Study Chair: Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai
  • Study Director: Usman Baber, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

July 10, 2019

Study Completion (Actual)

July 10, 2019

Study Registration Dates

First Submitted

October 15, 2014

First Submitted That Met QC Criteria

October 17, 2014

First Posted (Estimate)

October 21, 2014

Study Record Updates

Last Update Posted (Actual)

January 13, 2021

Last Update Submitted That Met QC Criteria

December 23, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 14-1383

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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