Trial to Assess the Effects of Vorapaxar (SCH 530348; MK-5348) in Preventing Heart Attack and Stroke in Patients With Atherosclerosis (TRA 2°P - TIMI 50) (P04737)

NCT00526474 | Completed Phase 3 Results DMC

• 4 other identifiers: P04737TRA 2°P - TIMI 502006-002942-12MK-5348-015
• Study Type: interventional
• Target: 26,449
• Locations: 0 countries
• Sites: N/A

Brief Summary

The study is designed to determine whether vorapaxar, when added to the existing standard of care (SOC) for preventing heart attack and stroke (eg, aspirin, clopidogrel) in participants with a known history of atherosclerosis, will yield additional benefit over the existing standard of care without vorapaxar in preventing heart attack and stroke. The study is also designed to assess risk of bleeding with vorapaxar added to the standard of care versus the standard of care alone.

Conditions

Atherosclerosis; Ischemia; Myocardial Infarction; Cerebrovascular Accident; Peripheral Arterial Disease

Outcome Measures

Primary Outcomes (1)

• Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, or Urgent Coronary Revascularization (UCR) Within 3 Years From Randomization

  The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death, MI, stroke, or UCR. A Clinical Endpoints Committee (CEC) reviewed and adjudicated each suspected efficacy endpoint event while blinded to treatment. Participants who did not have any endpoint event until last visit or participants who were lost to follow-up and had no event were censored at the time of last available information (last study visit). If a participant had a fatal event that was not part of a specific endpoint for analysis, they were censored at the time of death. The Kaplan-Meier estimate reports the percentage of participants who experienced CV death, MI, stroke, or UCR within 3 years from randomization.

  up to 3 years

Secondary Outcomes (15)

• Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, or Stroke Within 3 Years From Randomization

  up to 3 years

• Kaplan-Meier Estimate of the Percentage of Participants Who Met Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO) Moderate or Severe Bleeding Criteria Within 3 Years From Randomization

  up to 3 years

• Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Clinically Significant Bleeding Within 3 Years From Randomization

  up to 3 years

• Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Death From Any Cause, MI, Stroke, or UCR Within 3 Years From Randomization

  up to 3 years

• Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death or an MI Within 3 Years From Randomization

  up to 3 years

Study Arms (2)

Placebo

PLACEBO COMPARATOR

1 placebo tablet, orally, daily for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.

Drug: Placebo

Vorapaxar

EXPERIMENTAL

one 2.5 mg tablet daily, orally, for at least 1 year in addition to current treatment of atherosclerotic disease, which will be continued to be administered as per current standard of care.

Drug: Vorapaxar

Interventions

Vorapaxar DRUG

2.5-mg tablet daily for at least 1 year

Vorapaxar

Placebo DRUG

matching tablet daily for at least 1 year

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women at least 18 years old with evidence or a history of atherosclerosis involving the coronary, cerebral, or peripheral vascular systems by one or more of the following:
• history of myocardial infarction (heart attack)
• history of ischemic stroke (stroke due to a blocked artery)
• history of peripheral arterial disease

You may not qualify if:

• history of intracranial hemorrhage or of central nervous system (CNS) surgery, tumor, or aneurysm
• any bleeding disorder or abnormality
• sustained severe hypertension or valvular heart disease
• current or recent platelet count \<100,000 mm\^3
• planned or ongoing treatment with a blood thinning medication
• pregnancy
• any significant medical or physiological condition or abnormality that could put the subject at increased risk or limit the subject's ability to participate for the duration of the study

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• The TIMI Study Group: collaborator

Related Publications (19)

• Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

  PMID: 35224730 DERIVED

• Berg DD, Freedman BL, Bonaca MP, Jarolim P, Scirica BM, Goodrich EL, Sabatine MS, Morrow DA. Cardiovascular Biomarkers and Heart Failure Risk in Stable Patients With Atherothrombotic Disease: A Nested Biomarker Study From TRA 2 degrees P-TIMI 50. J Am Heart Assoc. 2021 May 4;10(9):e018673. doi: 10.1161/JAHA.120.018673. Epub 2021 Apr 22.

  PMID: 33884889 DERIVED

• Qamar A, Morrow DA, Creager MA, Scirica BM, Olin JW, Beckman JA, Murphy SA, Bonaca MP. Effect of vorapaxar on cardiovascular and limb outcomes in patients with peripheral artery disease with and without coronary artery disease: Analysis from the TRA 2 degrees P-TIMI 50 trial. Vasc Med. 2020 Apr;25(2):124-132. doi: 10.1177/1358863X19892690. Epub 2020 Jan 30.

  PMID: 32000630 DERIVED

• Xu H, Bonaca MP, Goodrich E, Scirica BM, Morrow DA. Efficacy and safety of vorapaxar for secondary prevention in low body weight in patients with atherosclerosis: analyses from the TRA 2 degrees P-TIMI 50 Trial. Eur Heart J Acute Cardiovasc Care. 2021 Apr 8;10(2):190-199. doi: 10.1177/2048872619883354. Epub 2019 Oct 23.

  PMID: 31642690 DERIVED

• Bonaca MP, Creager MA, Olin J, Scirica BM, Gilchrist IC Jr, Murphy SA, Goodrich EL, Braunwald E, Morrow DA. Peripheral Revascularization in Patients With Peripheral Artery Disease With Vorapaxar: Insights From the TRA 2 degrees P-TIMI 50 Trial. JACC Cardiovasc Interv. 2016 Oct 24;9(20):2157-2164. doi: 10.1016/j.jcin.2016.07.034.

  PMID: 27765312 DERIVED

• Bohula EA, Bonaca MP, Braunwald E, Aylward PE, Corbalan R, De Ferrari GM, He P, Lewis BS, Merlini PA, Murphy SA, Sabatine MS, Scirica BM, Morrow DA. Atherothrombotic Risk Stratification and the Efficacy and Safety of Vorapaxar in Patients With Stable Ischemic Heart Disease and Previous Myocardial Infarction. Circulation. 2016 Jul 26;134(4):304-13. doi: 10.1161/CIRCULATIONAHA.115.019861.

  PMID: 27440003 DERIVED

• Kidd SK, Bonaca MP, Braunwald E, De Ferrari GM, Lewis BS, Merlini PA, Murphy SA, Scirica BM, White HD, Morrow DA. Universal Classification System Type of Incident Myocardial Infarction in Patients With Stable Atherosclerosis: Observations From Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50. J Am Heart Assoc. 2016 Jul 18;5(7):e003237. doi: 10.1161/JAHA.116.003237.

  PMID: 27431644 DERIVED

• Berg DD, Bonaca MP, Braunwald E, Corbalan R, Goto S, Kiss RG, Murphy SA, Scirica BM, Spinar J, Morrow DA. Outcomes in Stable Patients With Previous Atherothrombotic Events Receiving Vorapaxar Who Experience a New Acute Coronary Event (from TRA2 degrees P-TIMI 50). Am J Cardiol. 2016 Apr 1;117(7):1055-8. doi: 10.1016/j.amjcard.2015.12.052. Epub 2016 Jan 14.

  PMID: 26876014 DERIVED

• Bonaca MP, Gutierrez JA, Creager MA, Scirica BM, Olin J, Murphy SA, Braunwald E, Morrow DA. Acute Limb Ischemia and Outcomes With Vorapaxar in Patients With Peripheral Artery Disease: Results From the Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-Thrombolysis in Myocardial Infarction 50 (TRA2 degrees P-TIMI 50). Circulation. 2016 Mar 8;133(10):997-1005. doi: 10.1161/CIRCULATIONAHA.115.019355. Epub 2016 Jan 29.

  PMID: 26826179 DERIVED

• Bohula EA, Aylward PE, Bonaca MP, Corbalan RL, Kiss RG, Murphy SA, Scirica BM, White H, Braunwald E, Morrow DA. Efficacy and Safety of Vorapaxar With and Without a Thienopyridine for Secondary Prevention in Patients With Previous Myocardial Infarction and No History of Stroke or Transient Ischemic Attack: Results from TRA 2 degrees P-TIMI 50. Circulation. 2015 Nov 17;132(20):1871-9. doi: 10.1161/CIRCULATIONAHA.114.015042. Epub 2015 Sep 3.

  PMID: 26338971 DERIVED

• Magnani G, Bonaca MP, Braunwald E, Dalby AJ, Fox KA, Murphy SA, Nicolau JC, Oude Ophuis T, Scirica BM, Spinar J, Theroux P, Morrow DA. Efficacy and safety of vorapaxar as approved for clinical use in the United States. J Am Heart Assoc. 2015 Mar 19;4(3):e001505. doi: 10.1161/JAHA.114.001505.

  PMID: 25792124 DERIVED

• Cavender MA, Scirica BM, Bonaca MP, Angiolillo DJ, Dalby AJ, Dellborg M, Morais J, Murphy SA, Ophuis TO, Tendera M, Braunwald E, Morrow DA. Vorapaxar in patients with diabetes mellitus and previous myocardial infarction: findings from the thrombin receptor antagonist in secondary prevention of atherothrombotic ischemic events-TIMI 50 trial. Circulation. 2015 Mar 24;131(12):1047-53. doi: 10.1161/CIRCULATIONAHA.114.013774. Epub 2015 Feb 13.

  PMID: 25681464 DERIVED

• Bonaca MP, Scirica BM, Braunwald E, Wiviott SD, Goto S, Nilsen DW, Bonarjee V, Murphy SA, Morrow DA. New ischemic stroke and outcomes with vorapaxar versus placebo: results from the TRA 2 degrees P-TIMI 50 trial. J Am Coll Cardiol. 2014 Dec 9;64(22):2318-26. doi: 10.1016/j.jacc.2014.07.997. Epub 2014 Dec 1.

  PMID: 25465417 DERIVED

• Bonaca MP, Scirica BM, Braunwald E, Wiviott SD, O'Donoghue ML, Murphy SA, Morrow DA. Coronary stent thrombosis with vorapaxar versus placebo: results from the TRA 2 degrees P-TIMI 50 trial. J Am Coll Cardiol. 2014 Dec 9;64(22):2309-17. doi: 10.1016/j.jacc.2014.09.037. Epub 2014 Dec 1.

  PMID: 25465416 DERIVED

• Bonaca MP, Scirica BM, Creager MA, Olin J, Bounameaux H, Dellborg M, Lamp JM, Murphy SA, Braunwald E, Morrow DA. Vorapaxar in patients with peripheral artery disease: results from TRA2degreesP-TIMI 50. Circulation. 2013 Apr 9;127(14):1522-9, 1529e1-6. doi: 10.1161/CIRCULATIONAHA.112.000679. Epub 2013 Mar 15.

  PMID: 23501976 DERIVED

• Morrow DA, Alberts MJ, Mohr JP, Ameriso SF, Bonaca MP, Goto S, Hankey GJ, Murphy SA, Scirica BM, Braunwald E; Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-TIMI 50 Steering Committee and Investigators. Efficacy and safety of vorapaxar in patients with prior ischemic stroke. Stroke. 2013 Mar;44(3):691-8. doi: 10.1161/STROKEAHA.111.000433. Epub 2013 Feb 8.

  PMID: 23396280 DERIVED

• Scirica BM, Bonaca MP, Braunwald E, De Ferrari GM, Isaza D, Lewis BS, Mehrhof F, Merlini PA, Murphy SA, Sabatine MS, Tendera M, Van de Werf F, Wilcox R, Morrow DA; TRA 2 degrees P-TIMI 50 Steering Committee Investigators. Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2 degrees P-TIMI 50 trial. Lancet. 2012 Oct 13;380(9850):1317-24. doi: 10.1016/S0140-6736(12)61269-0. Epub 2012 Aug 26.

  PMID: 22932716 DERIVED

• Morrow DA, Braunwald E, Bonaca MP, Ameriso SF, Dalby AJ, Fish MP, Fox KA, Lipka LJ, Liu X, Nicolau JC, Ophuis AJ, Paolasso E, Scirica BM, Spinar J, Theroux P, Wiviott SD, Strony J, Murphy SA; TRA 2P-TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012 Apr 12;366(15):1404-13. doi: 10.1056/NEJMoa1200933. Epub 2012 Mar 24.

  PMID: 22443427 DERIVED

• Morrow DA, Scirica BM, Fox KA, Berman G, Strony J, Veltri E, Bonaca MP, Fish P, McCabe CH, Braunwald E; TRA 2(o)P-TIMI 50 Investigators. Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)-TIMI 50 trial. Am Heart J. 2009 Sep;158(3):335-341.e3. doi: 10.1016/j.ahj.2009.06.027.

  PMID: 19699854 DERIVED

MeSH Terms

Conditions

Atherosclerosis; Ischemia; Myocardial Infarction; Stroke; Peripheral Arterial Disease

Interventions

vorapaxar

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Heart Diseases; Infarction; Necrosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Peripheral Vascular Diseases

Limitations and Caveats

Prior to the completion of the study, based on a communication from the Data and Safety Monitoring Board, all participants who had experienced a stroke either before or during the study had study drug discontinued.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2007
• First Posted: September 10, 2007
• Study Start: September 1, 2007
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: September 21, 2018
• Results First Posted: June 18, 2014

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share