The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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LPL100601, A Clinical Outcomes Study of Darapladib Versus Placebo in Subjects With Chronic Coronary Heart Disease to Compare the Incidence of Major Adverse Cardiovascular Events (MACE)

Conditions
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Atherosclerosis

Intervention / Treatment
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* Drug: Darapladib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Darapladib<br>Single daily oral tablet | Drug: Darapladib<br>* Lp-PLA2 inhibitor administered in addition to standard therapy<br>|
| Placebo Comparator: Placebo<br>Single daily oral tablet | Drug: Placebo<br>* Placebo administered in addition to standard therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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). | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 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) | 
| 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 | 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. | 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) | 
| Number of Participants With CV Death During the Time Period for Follow-up of CV Events | 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. | 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) | 
| Number of Participants With First Occurrence of MI (Fatal/Non-fatal) During the Time Period for Follow-up of CV Events | 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. | 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) | 
| Number of Participants With First Occurrence of Stroke (Fatal/Non-fatal) During the Time Period for Follow-up of CV Events | 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). | 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) | 
| 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 | 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). | 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) | 
| Number of Participants With All-cause Mortality During the Time Period for Vital Status | The number of participants with all-cause mortality was assessed. | From randomization until death or study completion (up to 4.49 years/average of 3.65 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart disease, Lp-PLA2 inhibitor, cardiovascular disease, coronary heart disease, CV risk, Atherosclerosis