Clinical trial NCT00527943: Trial to Assess the Effects of Vorapaxar (SCH 530348; MK-5348) in Preventing Heart Attack and Stroke in Particpants With Acute Coronary Syndrome (TRA•CER) (Study P04736)
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of SCH 530348 in Addition to Standard of Care in Subjects With Acute Coronary Syndrome: Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA•CER)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Atherosclerosis
Myocardial Ischemia
Myocardial Infarction
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Duke Clinical Research Institute
First posted: 2007-09-11
Enrollment: 12944
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study is designed to determine whether vorapaxar, when added to the existing standard of care (eg, aspirin, clopidogrel) for preventing heart attack and stroke in patients with acute coronary syndrome, will yield additional benefit over the existing standard of care 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.


Eligibility criteria: Inclusion Criteria:

Men and women at least 18 years old with current clinical manifestation of non-ST-segment-elevation myocardial infarction (heart attack) according to the following three criteria:

* current symptoms of cardiac ischemia (chest pain leading to cardiac ischemia or heart attack)

AND

* either of the following:

  * concurrent elevation of troponin I or T, or of creatine kinase - myocardial band (CK-MB) to a level above the upper limit of normal, OR
  * concurrent appropriate electrocardiographic evidence

AND

* any one (or more) of the following:

  * age \>= 55 years
  * documented history of prior heart attack or coronary revascularization (eg, angioplasty \[PCI\], coronary artery replacement \[CABG\])
  * diabetes (documented use of insulin or oral hypoglycemic\[s\])
  * documented history of peripheral arterial disease

Exclusion Criteria:

* 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

Primary outcomes:
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular Death, Myocardial Infarction, Stroke, Recurrent Ischemia With Re-hospitalization, and/or Urgent Coronary Revascularization Within 2 Years From Randomization
timeFrame: Up to 2 years
Secondary outcomes:
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular Death, Myocardial Infarction, and/or Stroke Within 2 Years From Randomization
timeFrame: up to 2 years
measure: 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 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Clinically Significant Bleeding Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, or UCR Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death or MI Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, RIR, or UCR Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, or UCR Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced an MI Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced RIR Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced UCR Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause Within 2 Years From Randomization
timeFrame: Up to 2 years
measure: Kaplan-Meier Estimate of the Percentage of Participants Who Experienced a Stroke Within 2 Years From Randomization
timeFrame: Up to 2 years
Other outcomes:
Locations:
Study officials:
References:
citation: Storey RF, Kotha J, Smyth SS, Moliterno DJ, Rorick TL, Moccetti T, Valgimigli M, Dery JP, Cornel JH, Thomas GS, Huber K, Harrington RA, Hord E, Judge HM, Chen E, Strony J, Mahaffey KW, Tricoci P, Becker RC, Jennings LK. Effects of vorapaxar on platelet reactivity and biomarker expression in non-ST-elevation acute coronary syndromes. The TRACER Pharmacodynamic Substudy. Thromb Haemost. 2014 May 5;111(5):883-91. doi: 10.1160/TH13-07-0624. Epub 2014 Jan 9.
citation: Valgimigli M, Tricoci P, Huang Z, Aylward PE, Armstrong PW, Van de Werf F, Leonardi S, White HD, Widimsky P, Harrington RA, Cequier A, Chen E, Lokhnygina Y, Wallentin L, Strony J, Mahaffey KW, Moliterno DJ. Usefulness and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (from the TRACER Trial). Am J Cardiol. 2014 Sep 1;114(5):665-73. doi: 10.1016/j.amjcard.2014.05.054. Epub 2014 Jun 18.
citation: Batra G, Lindback J, Becker RC, Harrington RA, Held C, James SK, Kempf T, Lopes RD, Mahaffey KW, Steg PG, Storey RF, Swahn E, Wollert KC, Siegbahn A, Wallentin L. Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes. J Am Coll Cardiol. 2022 Nov 1;80(18):1735-1747. doi: 10.1016/j.jacc.2022.08.767.
citation: 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.
citation: Inohara T, Pieper K, Wojdyla DM, Patel MR, Jones WS, Tricoci P, Mahaffey KW, James SK, Alexander JH, Lopes RD, Wallentin L, Ohman EM, Roe MT, Vemulapalli S. Incidence, timing, and type of first and recurrent ischemic events in patients with and without peripheral artery disease after an acute coronary syndrome. Am Heart J. 2018 Jul;201:25-32. doi: 10.1016/j.ahj.2018.03.013. Epub 2018 Mar 28.
citation: Armaganijan LV, Alexander KP, Huang Z, Tricoci P, Held C, Van de Werf F, Armstrong PW, Aylward PE, White HD, Moliterno DJ, Wallentin L, Chen E, Harrington RA, Strony J, Mahaffey KW, Lopes RD. Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial. Am Heart J. 2016 Aug;178:176-84. doi: 10.1016/j.ahj.2016.05.012. Epub 2016 Jun 9.
citation: Popma CJ, Sheng S, Korjian S, Daaboul Y, Chi G, Tricoci P, Huang Z, Moliterno DJ, White HD, Van de Werf F, Harrington RA, Wallentin L, Held C, Armstrong PW, Aylward PE, Strony J, Mahaffey KW, Gibson CM. Lack of Concordance Between Local Investigators, Angiographic Core Laboratory, and Clinical Event Committee in the Assessment of Stent Thrombosis: Results From the TRACER Angiographic Substudy. Circ Cardiovasc Interv. 2016 May;9(5):e003114. doi: 10.1161/CIRCINTERVENTIONS.115.003114.
citation: Vranckx P, White HD, Huang Z, Mahaffey KW, Armstrong PW, Van de Werf F, Moliterno DJ, Wallentin L, Held C, Aylward PE, Cornel JH, Bode C, Huber K, Nicolau JC, Ruzyllo W, Harrington RA, Tricoci P. Validation of BARC Bleeding Criteria in Patients With Acute Coronary Syndromes: The TRACER Trial. J Am Coll Cardiol. 2016 May 10;67(18):2135-2144. doi: 10.1016/j.jacc.2016.02.056.
citation: Mahaffey KW, Hager R, Wojdyla D, White HD, Armstrong PW, Alexander JH, Tricoci P, Lopes RD, Ohman EM, Roe MT, Harrington RA, Wallentin L. Meta-analysis of intracranial hemorrhage in acute coronary syndromes: incidence, predictors, and clinical outcomes. J Am Heart Assoc. 2015 Jun 18;4(6):e001512. doi: 10.1161/JAHA.114.001512.
citation: Bagai A, Huang Z, Lokhnygina Y, Harrington RA, Armstrong PW, Strony J, White HD, Leonardi S, Held C, Van de Werf F, Wallentin L, Tricoci P, Mahaffey KW. Magnitude of troponin elevation and long-term clinical outcomes in acute coronary syndrome patients treated with and without revascularization. Circ Cardiovasc Interv. 2015 Jun;8(6):e002314. doi: 10.1161/CIRCINTERVENTIONS.115.002314.
citation: White HD, Huang Z, Tricoci P, Van de Werf F, Wallentin L, Lokhnygina Y, Moliterno DJ, Aylward PE, Mahaffey KW, Armstrong PW. Reduction in overall occurrences of ischemic events with vorapaxar: results from TRACER. J Am Heart Assoc. 2014 Jul 10;3(4):e001032. doi: 10.1161/JAHA.114.001032.
citation: Whellan DJ, Tricoci P, Chen E, Huang Z, Leibowitz D, Vranckx P, Marhefka GD, Held C, Nicolau JC, Storey RF, Ruzyllo W, Huber K, Sinnaeve P, Weiss AT, Dery JP, Moliterno DJ, Van de Werf F, Aylward PE, White HD, Armstrong PW, Wallentin L, Strony J, Harrington RA, Mahaffey KW. Vorapaxar in acute coronary syndrome patients undergoing coronary artery bypass graft surgery: subgroup analysis from the TRACER trial (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome). J Am Coll Cardiol. 2014 Mar 25;63(11):1048-57. doi: 10.1016/j.jacc.2013.10.048. Epub 2013 Nov 21.
citation: Tricoci P, Huang Z, Held C, Moliterno DJ, Armstrong PW, Van de Werf F, White HD, Aylward PE, Wallentin L, Chen E, Lokhnygina Y, Pei J, Leonardi S, Rorick TL, Kilian AM, Jennings LH, Ambrosio G, Bode C, Cequier A, Cornel JH, Diaz R, Erkan A, Huber K, Hudson MP, Jiang L, Jukema JW, Lewis BS, Lincoff AM, Montalescot G, Nicolau JC, Ogawa H, Pfisterer M, Prieto JC, Ruzyllo W, Sinnaeve PR, Storey RF, Valgimigli M, Whellan DJ, Widimsky P, Strony J, Harrington RA, Mahaffey KW; TRACER Investigators. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012 Jan 5;366(1):20-33. doi: 10.1056/NEJMoa1109719. Epub 2011 Nov 13.
citation: TRA*CER Executive and Steering Committees. The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA*CER) trial: study design and rationale. Am Heart J. 2009 Sep;158(3):327-334.e4. doi: 10.1016/j.ahj.2009.07.001.