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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02270242
Recruitment Status : Completed
First Posted : October 21, 2014
Results First Posted : August 19, 2020
Last Update Posted : August 19, 2020
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Roxana Mehran, Icahn School of Medicine at Mount Sinai

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Supportive Care
Conditions Cardiovascular Disease
Interventional Cardiology
Interventions Drug: Aspirin
Drug: Placebo
Drug: ticagrelor
Enrollment 9006
Recruitment Details From July 2015 through December 2017, 9006 patients were enrolled, and 7119 underwent randomization after 3 months
Pre-assignment Details 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
Hide 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
Reason Not Completed
Withdrawal by Subject             18             25
Lost to Follow-up             41             27
Physician Decision             0             1
Arm/Group Title Placebo + Ticagrelor Aspirin + Ticagrelor Total
Hide 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 Number of Baseline Participants 3555 3564 7119
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3555 participants 3564 participants 7119 participants
65.2  (10.3) 65.1  (10.4) 65.1  (10.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
Female
846
  23.8%
852
  23.9%
1698
  23.9%
Male
2709
  76.2%
2712
  76.1%
5421
  76.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Nonwhite race Number Analyzed 3555 participants 3564 participants 7119 participants
1110
  31.2%
1086
  30.5%
2196
  30.8%
Unknown Number Analyzed 3555 participants 3564 participants 7119 participants
2445
  68.8%
2478
  69.5%
4923
  69.2%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
North America Number Analyzed 3555 participants 3564 participants 7119 participants
1484
  41.7%
1488
  41.8%
2972
  41.7%
Europe Number Analyzed 3555 participants 3564 participants 7119 participants
1251
  35.2%
1258
  35.3%
2509
  35.2%
China Number Analyzed 3555 participants 3564 participants 7119 participants
512
  14.4%
516
  14.5%
1028
  14.4%
India Number Analyzed 3555 participants 3564 participants 7119 participants
308
   8.7%
302
   8.5%
610
   8.6%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 3555 participants 3564 participants 7119 participants
28.6  (5.5) 28.5  (5.6) 28.6  (5.6)
Diabetes Mellitus  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
1319
  37.1%
1301
  36.5%
2620
  36.8%
Diabetes treated with Insulin  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
335
   9.4%
374
  10.5%
709
  10.0%
Chronic Kidney Disease (CKD)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3410 participants 3425 participants 6835 participants
572
  16.8%
573
  16.7%
1145
  16.8%
[1]
Measure Analysis Population Description: multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Anemia   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3405 participants 3423 participants 6828 participants
675
  19.8%
654
  19.1%
1329
  19.5%
[1]
Measure Analysis Population Description: multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Current smoker   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3553 participants 3562 participants 7115 participants
726
  20.4%
822
  23.1%
1548
  21.8%
[1]
Measure Analysis Population Description: multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Hypercholesterolemia  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
2157
  60.7%
2146
  60.2%
4303
  60.4%
Hypertension   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3554 participants 3563 participants 7117 participants
2580
  72.6%
2574
  72.2%
5154
  72.4%
[1]
Measure Analysis Population Description: multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Peripheral Arterial Disease (PAD)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
245
   6.9%
244
   6.8%
489
   6.9%
Previous Myocardial Infarction (MI)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
1020
  28.7%
1020
  28.6%
2040
  28.7%
Previous Percutaneous Coronary Intervention (PCI)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
1502
  42.3%
1496
  42.0%
2998
  42.1%
Previous Coronary Artery Bypass Graft (CABG)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3554 participants 3564 participants 7118 participants
362
  10.2%
348
   9.8%
710
  10.0%
[1]
Measure Analysis Population Description: multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
Multivessel Coronary Artery Disease (CAD)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
2272
  63.9%
2194
  61.6%
4466
  62.7%
Previous Major Bleeding Event  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3555 participants 3564 participants 7119 participants
31
   0.9%
32
   0.9%
63
   0.9%
Indication for PCI   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Asymptomatic Number Analyzed 3554 participants 3563 participants 7117 participants
234
   6.6%
223
   6.3%
457
   6.4%
Stable angina Number Analyzed 3554 participants 3563 participants 7117 participants
1047
  29.5%
999
  28.0%
2046
  28.7%
Unstable angina Number Analyzed 3554 participants 3563 participants 7117 participants
1249
  35.1%
1245
  34.9%
2494
  35.0%
NSTEMI (non-ST-segment elevation MI) Number Analyzed 3554 participants 3563 participants 7117 participants
1024
  28.8%
1096
  30.8%
2120
  29.8%
[1]
Measure Analysis Population Description: multinational trial involving over 9000 patients across 187 sites - some variables were missing and not entered into the system in some of the sites. active efforts were made to retrieve these variables but in some cases it was not possible.
1.Primary Outcome
Title Number of Participants With BARC Type 2, 3, or 5
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Data for the intention-to-treat population
Arm/Group Title Placebo + Ticagrelor Aspirin + Ticagrelor
Hide 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
Overall Number of Participants Analyzed 3555 3564
Measure Type: Count of Participants
Unit of Measure: Participants
141
   4.0%
250
   7.0%
2.Secondary Outcome
Title Number of Participants With Ischemic Episode
Hide Description Number of participants with first occurrence of confirmed all-cause death, non-fatal myocardial infarction or stroke.
Time Frame 12 months after randomization
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 3524 3515
Measure Type: Count of Participants
Unit of Measure: Participants
135
   3.8%
137
   3.9%
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
Hide 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 (%) Affected / at Risk (%)
Total   34/3524 (0.96%)   45/3515 (1.28%) 
Hide Serious Adverse Events
Placebo + Ticagrelor Aspirin + Ticagrelor
Affected / at Risk (%) Affected / at Risk (%)
Total   262/3555 (7.37%)   370/3564 (10.38%) 
Cardiac disorders     
Myocardial Infarction   95/3524 (2.70%)  97/3515 (2.76%) 
Injury, poisoning and procedural complications     
Stent Thrombosis, definite or probable   14/3524 (0.40%)  20/3515 (0.57%) 
Vascular disorders     
Ischemic Stroke   18/3524 (0.51%)  10/3515 (0.28%) 
BARC 235  [1]  141/3555 (3.97%)  250/3564 (7.01%) 
Indicates events were collected by systematic assessment
[1]
BARC type 2, 3, 5 bleeding
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + Ticagrelor Aspirin + Ticagrelor
Affected / at Risk (%) Affected / at Risk (%)
Total   0/3555 (0.00%)   0/3564 (0.00%) 
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Dr. Roxana Mehran
Organization: Icahn School of Medicine at Mount Sinai
Phone: 212-659-9691
EMail: roxana.mehran@mountsinai.org
Publications:
Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE 2nd, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS, Smith SC Jr, Jacobs AK, Halperin JL, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura R, Ornato JP, Page RL, Riegel B; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction); American College of Emergency Physicians; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; American Association of Cardiovascular and Pulmonary Rehabilitation; Society for Academic Emergency Medicine. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation. 2007 Aug 14;116(7):e148-304. Epub 2007 Aug 6. Erratum in: Circulation. 2008 Mar 4;117(9):e180.
Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation. 2004 Aug 3;110(5):588-636. Erratum in: Circulation. 2005 Apr 19;111(15):2013.
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Katus HA, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasché P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S. Third universal definition of myocardial infarction. Circulation. 2012 Oct 16;126(16):2020-35. doi: 10.1161/CIR.0b013e31826e1058. Epub 2012 Aug 24.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Roxana Mehran, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT02270242    
Other Study ID Numbers: GCO 14-1383
First Submitted: October 15, 2014
First Posted: October 21, 2014
Results First Submitted: July 10, 2020
Results First Posted: August 19, 2020
Last Update Posted: August 19, 2020