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

Cardiovascular Disease Clinical Trial

— TWILIGHT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02270242
• Other study ID #: GCO 14-1383
• Status: Completed
• Phase: Phase 4
• Start date: July 2015
• Est. completion date: July 10, 2019

Study information

• Verified date: December 2020
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9006
• Est. completion date: July 10, 2019
• Est. primary completion date: July 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Interventional Cardiology

Intervention

Drug:
• Aspirin

• Placebo

• ticagrelor

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	AstraZeneca

Country where clinical trial is conducted

United States, 

References & Publications (25)

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With BARC Type 2, 3, or 5	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	Number of Participants With Ischemic Episode	Number of participants with first occurrence of confirmed all-cause death, non-fatal myocardial infarction or stroke.	12 months after randomization