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The Stabilization Of pLaques usIng Darapladib-Thrombolysis In Myocardial Infarction 52 Trial (SOLID-TIMI 52)

This study has been completed.
Sponsor:
Collaborator:
The TIMI Study Group
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01000727
First received: October 22, 2009
Last updated: July 12, 2017
Last verified: June 2017
  Purpose
This study will test whether darapladib can safely lower the chances of having a cardiovascular event (such as a heart attack or urgent coronary revascularization (e.g. medical procedures performed to restore the normal blood flow in patients with atherosclerosis)) when treatment is started within 30 days after an acute coronary syndrome (also called ACS).

Condition Intervention Phase
Acute Coronary Syndrome Drug: Darapladib 160 mg Drug: Placebo Other: Standard Therapy Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Clinical Outcomes Study of Darapladib Versus Placebo in Subjects Following Acute Coronary Syndrome to Compare the Incidence of Major Adverse Cardiovascular Events (MACE).

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With First Occurrence of Any Event in the Composite of Major Coronary Events During the Time Period for Follow-up (FU) of Cardiovascular (CV) Event [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    Coronary heart disease (CHD) death=occurrence of a fatal myocardial infarction (MI), death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a nonischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Urgent coronary revascularization (CR) for MI=ischemic discomfort at rest that prompted CR during the same hospitalization or resulted in hospital transfer for the purpose of CR.


Secondary Outcome Measures:
  • Number of Participants With First Occurrence of Any Component of the Composite of Major Adverse Cardiovascular Events (Cardiovascular [CV] Death, Non-fatal MI or Non-fatal Stroke) During the Time Period for Follow-up of CV Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    CV death=death due to a CV cause, which included but was not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths. Acute MI=evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting >24 hours or results in death (in <24 hours).

  • Number of Participants With Cardiovascular Death During the Time Period for Follow-up of Cardiovascular Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    CV death is defined as a death due to a CV cause, which includes but is not limited to deaths resulting from stroke, arrhythmia, sudden death (witnessed/unwitnessed), MI, heart failure, pulmonary embolism, peripheral arterial disease, or complications of a CV procedure. Deaths not clearly attributable to non-CV causes are considered to be CV deaths.

  • Number of Participants With First Occurrence of MI (Fatal/Nonfatal) During the Time Period for Follow-up of Cardiovascular Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI.

  • Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of Cardiovascular Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    Stroke is defined as the presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting >24 hours or results in death (in <24 hours).

  • Number of Participants With CHD Death During the Time Period for Follow-up of Cardiovascular Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    CHD death is defined as the occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death.

  • Number of Participants With Urgent Coronary Revascularization for Myocardial Ischemia During the Time Period for Follow-up of Cardiovascular Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    Urgent coronary revascularization for myocardial ischemia is defined as ischemic discomfort at rest that prompts coronary revascularization (PCI or coronary artery bypass graft [CABG]) during the same hospitalization or resulting in hospital transfer for the purpose of coronary revascularization. PCI is defined as any attempt at revascularization even if not successful (e.g., angioplasty, atherectomy or stenting).

  • Number of Participants With First Occurrence of Any Event in the Composite of Total Coronary Events (CHD Death, Non-fatal MI, Hospitalization for Unstable Angina, or Any Coronary Revascularization Procedure) During the Time Period for FU of CV Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    CHD death, acute MI, and prior MI diagnosed post-randomization are defined in the primary endpoint (major coronary events). Hospitalization for unstable angina=one of the following, but not fulfilling the criteria for MI: ischemic discomfort at rest associated with electrocardiogram (ECG) changes leading to hospitalization; ischemic discomfort at rest regardless of ECG changes leading to hospitalization and revascularization during the same admission; ischemic discomfort at rest in hospital associated with ECG changes; ischemic discomfort at rest in hospital without ECG changes resulting in revascularization during the same admission. NOTE: The event was not considered to be unstable angina if, after invasive/non-invasive testing or other diagnostic testing, the discomfort was found not to be caused by myocardial ischemia. Coronary revascularization procedures exclude PCI planned prior to randomization but performed after randomization.

  • Number of Participants With First Occurrence of Any Coronary Revascularization Procedures (Excluding Coronary Revascularization Planned Prior to Randomization, But Performed After Randomization) During the Time Period for Follow-up of Cardiovascular Event [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    All coronary revascularization procedures (except for PCI planned prior to randomization but performed after randomization) are included. Examples include coronary artery bypass graft, balloon angioplasty and stenting. The number of participants, with first occurrence of any coronary revascularization procedures, were reported.

  • Number of Participants With First Occurrence of Any Component of the Composite of All-cause Mortality, Non-fatal MI, or Nonfatal Stroke During the Time Period for Follow-up of Cardiovascular Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. Stroke=presence of a new focal neurologic deficit thought to be of vascular origin, with signs/symptoms lasting >24 hours or results in death (in <24 hours).

  • Number of Participants With First Occurrence of Any Event in the Composite of CHD Death and Non-fatal MI During the Time Period for Follow-up of Cardiovascular Events [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    Acute MI is defined as evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia. Prior MI diagnosed post-randomization (e.g., silent MI)=the development of new pathological Q waves with/without symptoms OR imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischemic cause (pre-event imaging data required for verification of new abnormality), OR pathological findings of a healed/healing MI. CHD death is defined as the occurrence of a fatal MI, death caused by documented cardiac arrest, death resulting from heart failure in a participant with known CHD, death from other forms of acute/chronic CHD, unwitnessed death of unknown origin, or sudden death.

  • Number of Participants With All-cause Mortality During the Time Period for Vital Status [ Time Frame: From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 3.80 years) ]
    Number of participants who died, during the vital status time-period were reported. The participants who were known to have died, date of death was used; for participants who completed the study the study completion date was used; for participants who withdrew from the study where vital status was ascertained , and are known to have not died , the last known date to be alive was used and for participants whom vital status was not ascertained, following study withdrawal the study withdrawal date was used.


Enrollment: 13026
Study Start Date: December 1, 2009
Study Completion Date: April 24, 2014
Primary Completion Date: April 1, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Darapladib 160 mg
Single daily oral tablet
Drug: Darapladib 160 mg
Lp-PLA2 inhibitor
Other Name: SB-480848
Other: Standard Therapy
Guideline mandated therapy for individual's condition
Placebo Comparator: Placebo
Single daily oral tablet
Drug: Placebo
Placebo administered
Other: Standard Therapy
Guideline mandated therapy for individual's condition

Detailed Description:
Subjects who qualify for the study will be randomized 1:1 to either darapladib or placebo administered in addition to standard therapy. Following the baseline visit, subjects will be expected to return for clinic visits at 1 month, 3 months, 6 months and every 6 months until the end of the study.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed written informed consent.
  • Men or women at least 18 years old (in Taiwan, at least 20 years old). Women must be post-menopausal or using a highly effective method for avoidance of pregnancy.
  • Hospitalization for acute coronary syndrome (ACS) within 30 days prior to study entry.
  • Clinically stable for 24 hours prior to study entry.
  • A planned percutaneous coronary intervention (PCI) should be performed prior to study entry, whenever possible.
  • At least one of the following:
  • At least 60 years old.
  • Myocardial infarction prior to the qualifying ACS event.
  • Diabetes mellitus requiring treatment with medication.
  • Diagnosed mild or moderate reduction in kidney function.
  • Cerebrovascular disease (carotid artery disease or ischemic stroke more than 3 months prior to study entry) OR peripheral artery disease.

Exclusion Criteria:

  • ACS symptoms or lab results not believed to be caused by a narrowing or blocked coronary artery.
  • No major coronary artery with a blockage of more than 50% (unless all stenoses are successfully treated by PCI).
  • Planned coronary artery bypass graft (CABG) surgery, or CABG surgery performed after the qualifying ACS event and prior to study entry.
  • Certain types of liver disease.
  • Severe reduction in kidney function OR removal of a kidney OR kidney transplant.
  • Severe heart failure.
  • Blood pressure higher than normal despite lifestyle changes and treatment with medications.
  • Any life-threatening disease with a life expectancy of less than 2 years (other than heart disease) that may prevent the subject from completing the study.
  • Severe asthma that is poorly controlled with medication.
  • Pregnancy (Note: A pregnancy test will be performed on all non-sterile women prior to study entry).
  • Previous severe allergic reaction to food, medications, drink, insect stings, etc.
  • Drug or alcohol abuse within the past 6 months. Mental/psychological impairment that may prevent the subject from complying with study procedures or understanding the goal and potential risks of participating in the study.
  • Certain medications that may interfere with the study medication (these will be identified by the study doctor).
  • If both birth parents are at least 50% Japanese, Chinese, or Korean ancestry, must have a blood sample collected for Lp-PLA2 activity. Those with Lp-PLA2 activity less than or equal to 20.0 nmol/min/mL are excluded.
  • Previously took darapladib (SB-480848).
  • Participation in a study of an investigational medication within the past 30 days.
  • Current participation in a study of an investigational device.
  • Any other reason the investigator deems the subject should not participate in 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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01000727

  Show 916 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
The TIMI Study Group
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 480848/033
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 480848/033
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 480848/033
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 480848/033
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 480848/033
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 480848/033
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01000727     History of Changes
Other Study ID Numbers: 480848/033
Study First Received: October 22, 2009
Results First Received: June 9, 2017
Last Updated: July 12, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
URL: http://

Keywords provided by GlaxoSmithKline:
Atherosclerosis
Heart disease
Cardiovascular disease
Lp-PLA2 inhibitor
The TIMI Study Group
Coronary Heart Disease (CHD)
Acute Coronary Syndrome (ACS)

Additional relevant MeSH terms:
Syndrome
Acute Coronary Syndrome
Disease
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Darapladib
Phospholipase A2 Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 21, 2017