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)

This study has been terminated.
(The trial was terminated at the request of the Data and Safety Monitoring Board.)
Sponsor:
Collaborator:
Duke Clinical Research Institute
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00527943
First received: September 7, 2007
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Atherosclerosis
Myocardial Ischemia
Myocardial Infarction
Drug: Vorapaxar
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular (CV) death, myocardial infarction (MI), stroke, recurrent ischemia with re-hospitalization (RIR), and/or urgent coronary revascularization (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 at least 1 of the components of the primary composite efficacy endpoint within 2 years from randomization.


Secondary Outcome Measures:
  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular Death, Myocardial Infarction, and/or Stroke Within 2 Years From Randomization [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: cardiovascular (CV) death, myocardial infarction (MI), and/or stroke. A 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 at least 1 of the components of the secondary composite efficacy endpoint within 2 years from randomization.

  • 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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Adverse events were categorized as "bleeding events" if the intensity of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the GUSTO cooperative group criteria as follows: Mild , Moderate or Severe and the grading was adjudicated by the CEC. The Kaplan-Meier estimate reports the percentage of participants who experienced GUSTO moderate or severe bleeding within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Clinically Significant Bleeding Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Adverse events were categorized as "bleeding events" if the intensity of the event was other or more than would be normally expected in the given situation (eg, mild nosebleed in a person who does not normally have nosebleeds, greater bruising than expected for a given injury, greater volume of blood loss than expected for a given procedure). The investigator graded the intensity of bleeding events according to the Thrombolysis in Myocardial Infarction (TIMI) Study Group criteria as major, minor or other. "Clinically Significant Bleeding" was defined as the composite of TIMI Major bleeding, TIMI Minor bleeding, or bleeding that required unplanned medical or surgical treatment or unplanned laboratory evaluation even if it did not meet the criteria for TIMI major or minor bleeding. The Kaplan-Meier estimate reports the percentage of participants who experienced clinically significant bleeding within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, or UCR Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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 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 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death or MI Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: CV death or MI. A 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 or MI within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, RIR, or UCR Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: all-cause death, MI, stroke, RIR, or UCR. A 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). The Kaplan-Meier estimate reports the percentage of participants who experienced all-cause death, MI, stroke, RIR, or UCR within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, or UCR Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the first occurrence of any of the following clinical outcomes was recorded: all-cause death, MI, stroke, or UCR. A 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). The Kaplan-Meier estimate reports the percentage of participants who experienced all-cause Death, MI, stroke, or UCR I within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the CV death (if reported) was recorded. A 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 within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced an MI Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the first occurrence of an MI was recorded. A 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 an MI within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced RIR Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the first occurrence of RIR was recorded. A 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 RIR within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced UCR Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to the first occurrence of UCR was recorded. A 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 UCR within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to death from any cause was recorded. A 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). The Kaplan-Meier estimate reports the percentage of participants who died from any cause within 2 years from randomization.

  • Kaplan-Meier Estimate of the Percentage of Participants Who Experienced a Stroke Within 2 Years From Randomization [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    The time (in days) from study start to first experience of a stroke was recorded. A 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 a stroke within 2 years from randomization.


Enrollment: 12944
Study Start Date: December 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Loading oral dose of one 40 mg vorapaxar placebo tablet on Day 1, then one 2.5 mg vorapaxar placebo tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Drug: Placebo
oral tablets; matching placebo for vorapaxar; loading and maintenance dosing; once daily for at least 1 year
Experimental: Vorapaxar
Loading oral dose of one 40 mg vorapaxar tablet on Day 1, then one 2.5 mg vorapaxar tablet daily, orally for at least 1 year in addition to current treatment of acute coronary syndrome, which will be continued to be administered as per current stand of care.
Drug: Vorapaxar
oral tablets; 40-mg loading dose on first day, followed by 2.5 mg once daily for at least 1 year
Other Names:
  • SCH 530348
  • MK-5348

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00527943     History of Changes
Other Study ID Numbers: P04736, TRA•CER, 2006-002809-31, MK-5348-014
Study First Received: September 7, 2007
Results First Received: May 9, 2014
Last Updated: May 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Infarction
Myocardial Ischemia
Coronary Artery Disease
Myocardial Infarction
Acute Coronary Syndrome
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Ischemia
Pathologic Processes
Necrosis
Heart Diseases
Coronary Disease
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on September 16, 2014