Clincosm LogoSign in Get a demo

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

Sponsor
Icahn School of Medicine at Mount Sinai (Other)
Overall Status
Completed
CT.gov ID
NCT02270242
Collaborator
AstraZeneca (Industry)
9,006
Enrollment
1
Location
2
Arms
48.3
Duration (Months)
186.5
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
9006 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Supportive Care
Official Title:
Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention
Study Start Date :
Jul 1, 2015
Actual Primary Completion Date :
Jul 10, 2019
Actual Study Completion Date :
Jul 10, 2019

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With BARC Type 2, 3, or 5 [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).

    Secondary Outcome Measures

    1. Number of Participants With Ischemic Episode [12 months after randomization]

      Number of participants with first occurrence of confirmed all-cause death, non-fatal myocardial infarction or stroke.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Icahn School of Medicine at Mount Sinai New York New York United States 10029

    Sponsors and Collaborators

    • Icahn School of Medicine at Mount Sinai
    • AstraZeneca

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Roxana Mehran, Professor, Icahn School of Medicine at Mount Sinai
    ClinicalTrials.gov Identifier:
    NCT02270242
    Other Study ID Numbers:
    • GCO 14-1383
    First Posted:
    Oct 21, 2014
    Last Update Posted:
    Jan 13, 2021
    Last Verified:
    Dec 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Roxana Mehran, Professor, Icahn School of Medicine at Mount Sinai
    PCI
    DAPT
    ticagrelor
    aspirin
    Additional relevant MeSH terms:
    Cardiovascular Diseases
    Aspirin
    Ticagrelor

    Study Results

    Participant Flow

    Recruitment Details From July 2015 through December 2017, 9006 patients were enrolled, and 7119 underwent randomization after 3 months
    Pre-assignment Detail 1887 excluded from randomization (106 lost to follow up, 243 had adverse events between enrollment and randomization: a) myocardial infarction, stroke or death, b) revascularizations, and/or c) BARC type 3b or higher bleedings, 1148 were not adherent to DAPT, 267 withdrew consent or declined to participate, and 123 had other reasons.)
    Arm/Group Title Placebo + Ticagrelor Aspirin + Ticagrelor
    Arm/Group Description placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
    Period Title: Overall Study
    STARTED 3555 3564
    COMPLETED 3496 3511
    NOT COMPLETED 59 53

    Baseline Characteristics

    Arm/Group Title Placebo + Ticagrelor Aspirin + Ticagrelor Total
    Arm/Group Description placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months Total of all reporting groups
    Overall Participants 3555 3564 7119
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65.2
    (10.3)
    65.1
    (10.4)
    65.1
    (10.3)
    Sex: Female, Male (Count of Participants)
    Female
    846
    23.8%
    852
    23.9%
    1698
    23.9%
    Male
    2709
    76.2%
    2712
    76.1%
    5421
    76.1%
    Race/Ethnicity, Customized (Count of Participants)
    Nonwhite race
    1110
    31.2%
    1086
    30.5%
    2196
    30.8%
    Unknown
    2445
    68.8%
    2478
    69.5%
    4923
    69.2%
    Region of Enrollment (Count of Participants)
    North America
    1484
    41.7%
    1488
    41.8%
    2972
    41.7%
    Europe
    1251
    35.2%
    1258
    35.3%
    2509
    35.2%
    China
    512
    14.4%
    516
    14.5%
    1028
    14.4%
    India
    308
    8.7%
    302
    8.5%
    610
    8.6%
    Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    28.6
    (5.5)
    28.5
    (5.6)
    28.6
    (5.6)
    Diabetes Mellitus (Count of Participants)
    Count of Participants [Participants]
    1319
    37.1%
    1301
    36.5%
    2620
    36.8%
    Diabetes treated with Insulin (Count of Participants)
    Count of Participants [Participants]
    335
    9.4%
    374
    10.5%
    709
    10%
    Chronic Kidney Disease (CKD) (Count of Participants)
    Count of Participants [Participants]
    572
    16.1%
    573
    16.1%
    1145
    16.1%
    Anemia (Count of Participants)
    Count of Participants [Participants]
    675
    19%
    654
    18.4%
    1329
    18.7%
    Current smoker (Count of Participants)
    Count of Participants [Participants]
    726
    20.4%
    822
    23.1%
    1548
    21.7%
    Hypercholesterolemia (Count of Participants)
    Count of Participants [Participants]
    2157
    60.7%
    2146
    60.2%
    4303
    60.4%
    Hypertension (Count of Participants)
    Count of Participants [Participants]
    2580
    72.6%
    2574
    72.2%
    5154
    72.4%
    Peripheral Arterial Disease (PAD) (Count of Participants)
    Count of Participants [Participants]
    245
    6.9%
    244
    6.8%
    489
    6.9%
    Previous Myocardial Infarction (MI) (Count of Participants)
    Count of Participants [Participants]
    1020
    28.7%
    1020
    28.6%
    2040
    28.7%
    Previous Percutaneous Coronary Intervention (PCI) (Count of Participants)
    Count of Participants [Participants]
    1502
    42.3%
    1496
    42%
    2998
    42.1%
    Previous Coronary Artery Bypass Graft (CABG) (Count of Participants)
    Count of Participants [Participants]
    362
    10.2%
    348
    9.8%
    710
    10%
    Multivessel Coronary Artery Disease (CAD) (Count of Participants)
    Count of Participants [Participants]
    2272
    63.9%
    2194
    61.6%
    4466
    62.7%
    Previous Major Bleeding Event (Count of Participants)
    Count of Participants [Participants]
    31
    0.9%
    32
    0.9%
    63
    0.9%
    Indication for PCI (Count of Participants)
    Asymptomatic
    234
    6.6%
    223
    6.3%
    457
    6.4%
    Stable angina
    1047
    29.5%
    999
    28%
    2046
    28.7%
    Unstable angina
    1249
    35.1%
    1245
    34.9%
    2494
    35%
    NSTEMI (non-ST-segment elevation MI)
    1024
    28.8%
    1096
    30.8%
    2120
    29.8%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With BARC Type 2, 3, or 5
    Description 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).
    Time Frame 12 months after randomization

    Outcome Measure Data

    Analysis Population Description
    Data for the intention-to-treat population
    Arm/Group Title Placebo + Ticagrelor Aspirin + Ticagrelor
    Arm/Group Description placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
    Measure Participants 3555 3564
    Count of Participants [Participants]
    141
    4%
    250
    7%
    2. Secondary Outcome
    Title Number of Participants With Ischemic Episode
    Description Number of participants with first occurrence of confirmed all-cause death, non-fatal myocardial infarction or stroke.
    Time Frame 12 months after randomization

    Outcome Measure Data

    Analysis Population Description
    data for the per-protocol population , i.e., the participants who underwent randomization and had no major deviations from the protocol.
    Arm/Group Title Placebo + Ticagrelor Aspirin + Ticagrelor
    Arm/Group Description placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
    Measure Participants 3524 3515
    Count of Participants [Participants]
    135
    3.8%
    137
    3.8%

    Adverse Events

    Time Frame 1 year
    Adverse Event Reporting Description All bleeding AE were reported in the intention-to-treat (ITT) cohort. - Placebo + Ticagrelor (N=3555) and Aspirin + Ticagrelor (N=3564) All ischemic AE were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515) All-cause mortality were reported in the per protocol (PP) cohort. - Placebo + Ticagrelor (N=3524) and Aspirin + Ticagrelor (N=3515)
    Arm/Group Title Placebo + Ticagrelor Aspirin + Ticagrelor
    Arm/Group Description placebo pill daily p.o. for 12 months - match for enteric coated aspirin 81mg-100mg and ticagrelor 90mg tablet bid for 12 months enteric coated aspirin 81mg-100mg daily p.o. for 12 months and ticagrelor 90mg tablet bid for 12 months
    All Cause Mortality
    Placebo + Ticagrelor Aspirin + Ticagrelor
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 34/3524 (1%) 45/3515 (1.3%)
    Serious Adverse Events
    Placebo + Ticagrelor Aspirin + Ticagrelor
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 262/3555 (7.4%) 370/3564 (10.4%)
    Cardiac disorders
    Myocardial Infarction 95/3524 (2.7%) 97/3515 (2.8%)
    Injury, poisoning and procedural complications
    Stent Thrombosis, definite or probable 14/3524 (0.4%) 20/3515 (0.6%)
    Vascular disorders
    Ischemic Stroke 18/3524 (0.5%) 10/3515 (0.3%)
    BARC 235 141/3555 (4%) 250/3564 (7%)
    Other (Not Including Serious) Adverse Events
    Placebo + Ticagrelor Aspirin + Ticagrelor
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3555 (0%) 0/3564 (0%)

    Limitations/Caveats

    Limitations include lack of power to detect differences in the risk of important yet rare clinical events, e.g stent thrombosis and stroke; and trial may not be generalizable to all patients undergoing PCI due to high risk criteria.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Investigator remains responsible & has final approval for any publication and can publish/present results but shall submit manuscript/material proposed for publication/presentation relating to results to AZ for review ≤45 days prior to submission. AZ has 45 days to respond with comments. If requested by AZ, Investigator shall delay submission for further period ≤45 days, for deemed appropriate measures to establish/preserve parties' proprietary rights in intellectual property disclosed.

    Results Point of Contact

    Name/Title Dr. Roxana Mehran
    Organization Icahn School of Medicine at Mount Sinai
    Phone 212-659-9691
    Email roxana.mehran@mountsinai.org
    Responsible Party:
    Roxana Mehran, Professor, Icahn School of Medicine at Mount Sinai
    ClinicalTrials.gov Identifier:
    NCT02270242
    Other Study ID Numbers:
    • GCO 14-1383
    First Posted:
    Oct 21, 2014
    Last Update Posted:
    Jan 13, 2021
    Last Verified:
    Dec 1, 2020