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)

Myocardial Infarction Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00527943
• Other study ID #: P04736
• Secondary ID: TRA•CER2006-0028
• Status: Terminated
• Phase: Phase 3
• Start date: December 1, 2007
• Est. completion date: July 1, 2011

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12944
• Est. completion date: July 1, 2011
• Est. primary completion date: July 1, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Atherosclerosis
• Coronary Artery Disease
• Infarction
• Ischemia
• Myocardial Infarction
• Myocardial Ischemia

Intervention

Drug:
• Vorapaxar
oral tablets; 40-mg loading dose on first day, followed by 2.5 mg once daily for at least 1 year
• Placebo
oral tablets; matching placebo for vorapaxar; loading and maintenance dosing; once daily for at least 1 year

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.	Duke Clinical Research Institute

References & Publications (2)

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 re — View 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 w — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Cardiovascular Death, Myocardial Infarction, and/or Stroke Within 2 Years From Randomization	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.	up to 2 years
Secondary	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	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced Clinically Significant Bleeding Within 2 Years From Randomization	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death, MI, Stroke, or UCR Within 2 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 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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death or MI Within 2 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 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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, RIR, or UCR Within 2 Years From Randomization	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced All-cause Death, MI, Stroke, or UCR Within 2 Years From Randomization	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced CV Death Within 2 Years From Randomization	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced an MI Within 2 Years From Randomization	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced RIR Within 2 Years From Randomization	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced UCR Within 2 Years From Randomization	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Died From Any Cause Within 2 Years From Randomization	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.	Up to 2 years
Secondary	Kaplan-Meier Estimate of the Percentage of Participants Who Experienced a Stroke Within 2 Years From Randomization	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.	Up to 2 years