The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial
- Registration Number
- NCT00799903
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
This study will test whether darapladib can safely lower the chances of having a cardiovascular event (such as a heart attack or stroke) in people with coronary heart disease.
- 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, and every 6 months until the end of the study. Average time in the study for an individual subject is expected to be about 3 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15828
- Men or women at least 18 years old. Women must be post-menopausal or using a highly effective method for avoidance of pregnancy.
- Current treatment with statin therapy unless the study doctor determines statins are not appropriate for the subject.
- Chronic coronary heart disease
- At least one of the following:
- At least 60 years old
- Diabetes requiring treatment with medication
- Low HDL cholesterol ("good cholesterol")
- Currently smoke cigarettes or stopped smoking within the past 3 months
- 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 arterial disease.
- Planned coronary revascularization (such as stent placement or heart bypass) or any other major surgical procedure.
- 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 expected to result in death within the next 2 years (other than heart disease)
- Severe asthma that is poorly controlled with medication
- Pregnant (Note: A pregnancy test will be performed on all non-sterile women prior to study entry)
- Previous severe allergic response to food, drink, insect stings, etc.
- Drug or alcohol abuse within the past 6 months OR 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)
- Participation in a study of an investigational medication within the past 30 days
- Current participation in a study of an investigational device
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Darapladib Darapladib Single daily oral tablet Placebo Placebo Single daily oral tablet
- Primary Outcome Measures
Name Time Method Number of Participants With First Occurrence of Any Component of the Composite of Major Adverse Cardiovascular Events (Cardiovascular [CV] Death, Non-fatal Myocardial Infarction [MI] or Non-fatal Stroke) During the Time Period for Follow-up of CV Events From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 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).
- Secondary Outcome Measures
Name Time Method Number of Participants With First Occurrence of Any Event in the Composite of Major Coronary Events (Coronary Heart Disease [CHD] Death, Non-fatal MI, or Urgent Coronary Revascularization [CR] for MI) During the Time Period for Follow-up (FU) of CV Events From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years) CHD death=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. 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. Urgent CR for MI=ischemic discomfort at rest that prompted CR (percutaneous coronary intervention \[PCI: any attempt at CR even if not successful\] or coronary artery bypass graft) during the same hospitalization or resulted in hospital transfer for the purpose of CR.
Number of Participants With CV Death During the Time Period for Follow-up of CV Events From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years) CV death is defined as a 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.
Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of CV Events From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 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 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 Time Period for FU of CV Events From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 years) CHD death, acute MI, and prior MI are defined in the previous secondary 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 is found not to be caused by myocardial ischemia.
Number of Participants With All-cause Mortality During the Time Period for Vital Status From randomization until death or study completion (up to 4.49 years/average of 3.65 years) The number of participants with all-cause mortality was assessed.
Number of Participants With First Occurrence of MI (Fatal/Non-fatal) During the Time Period for Follow-up of CV Events From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 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 Any Component of the Composite of All-cause Mortality, Non-fatal MI, or Non-fatal Stroke During the Time Period for Follow-up of CV Events From randomization until the End-of-Treatment visit or the last date on which endpoints were able to be assessed (up to 4.25 years/average of 3.51 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).
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Paisley, United Kingdom