Acute Coronary syndrome arterial disease
Conditions
Interventions
Cohort A (n=3000): dalcetrapib 600mg
Cohort B (n=3000): placebo
Sponsors
DalCor Pharma UK Ltd
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Subjects with the appropriate genetic background and recently hospitalized for ACS (between 1 and 3 months following the index event), will be enrolled in this trial. ACS is defined as the occurrence of at least one of the following events: A) Myocardial Infarction (MI) Spontaneous MI --> A diagnosis of a qualifying MI event will be defined by a rise and/or fall of cardiac biomarkers (preferably cardiac troponin) with at least one determination greater than the 99th percentile upper reference limit (URL) plus at least one of the following described below: a. Symptoms of myocardial ischemia, or b. New or presumed new significant ST-segment-T wave (ST-T) changes or new left bundle branch block, or c. Development of pathological Q waves in the ECG, or d. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality, or e. Identification of an intracoronary thrombus by angiography Procedure-Related MI after Percutaneous Coronary Intervention (PCI) --> A procedure-related MI after PCI is defined as an increase of cardiac troponin values with at least one determination greater than 5 times the 99th percentile URL in patients with normal baseline values (less than or equal to 99th percentile URL) or a rise of cardiac troponin values > 20% if the baseline values are elevated and are stable or falling; plus at least one of the following described below: a. Symptoms suggestive of myocardial ischemia b. New ischemic ECG changes c. Imaging demonstration of new loss of viable myocardium or new regional wall motion abnormality d. Angiographic findings consistent with a procedural complication B) Hospitalization for ACS (ECG Abnormalities without Biomarkers): A diagnosis of a qualifying ACS event without increases in cardiac biomarkers will require admission to hospital or emergency room (exceeding 23hrs) with symptoms presumed to be caused by myocardial ischemia with an accelerating tempo in the prior 48hrs and/or prolonged (at least 20min) rest chest discomfort and new ECG findings (or presumed new if no prior ECG available) as described below and at least one of the following: a. At least 50% stenosis of an epicardial coronary artery b. Positive exercise or pharmacologic stress indicating reversible ischemia c. Presence of pathologic Q-waves on ECG In addition, the following inclusion criteria apply: 1. Both male and female subjects age 45 years and over at screening visit (V1) 2. Signed informed consent obtained prior to any study specific screening procedures 3. AA genotype at variant rs1967309 in the ADCY9 gene as determined by cobas® ADCY9 Genotype CTA testing, conducted at a designated investigational testing site (ITS) 4. Clinically stable, ie, free of ischemic symptoms at rest or with minimal exertion for at least 1 week prior to randomization 5. Prior to randomization, subject must have evidence of guidelines-based management of LDL-C, at a minimum to include medical and dietary treatment to a target level of LDL-C
Exclusion criteria
Exclusion criteria: 1. Females who are pregnant (negative pregnancy test required for all women of child-bearing potential at Visit 2, Day 0) or breast-feeding 2. Women of child-bearing potential (women who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using at least one method of contraception. 3. New York Heart Association (NYHA) Class III or IV heart failure 4. Last known hemoglobin 180mmHg and/or diastolic blood pressure >110mmHg by the time of randomization despite anti-hypertensive therapy 7. Last known serum triglyceride level >500mg/dl (>5.65mmol/L) as assessed within 6 months prior to randomization 8. Last known hemoglobin A1c (HbA1c) > 10% as assessed within 6 months prior to randomization 9. Subjects with clinically apparent liver disease, eg, jaundice, cholestasis, hepatic synthetic impairment, or active hepatitis 10. Last known ALT or AST level > 3 times the upper limit of normal (ULN) or last known alkaline phosphatase level > 2 times the ULN as assessed within 6 months prior to randomization (excluding index event) 11. History of persistent and unexplained creatine phosphokinase (CPK) levels > 3 times the ULN as assessed within 6 months prior to randomization (excluding index event) 12. Last known serum creatinine > 2.2mg/dl (195*mol/l) as assessed within 6 months prior to randomization 13. Previous exposure to anacetrapib or evacetrapib or documented allergic reaction to any CETP inhibitor 14. History of malignancy (except for curatively treated basal cell or squamous cell carcinoma of the skin) during the 1 year prior to the screening 15. Any clinically significant medical condition that according to the investigator could interfere with the conduct of the study 16. Subjects whose life expectancy is shorter than 3 years 17. Presence of any last known laboratory value as evaluated prior to randomization that is considered by the investigator to potentially limit the patient*s successful participation in the study 18. Current alcohol or drug abuse or history thereof within 2 years prior to screening that would likely interfere with compliance, based on investigator assessment 19. Subjects who have received any investigational drug within 1 month of randomization, or who expect to participate in any other investigational drug or device study during the conduct of this trial 20. Subjects unable or unwilling to comply with protocol requirements, or deemed by the investigator to be unfit for the study 21. Subjects who have undergone coronary artery bypass graft (CABG) surgery between the index event and randomization
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of this study is the time to first occurrence of any component of the composite endpoint, as adjudicated by the Clinical Endpoint Committee. Components of the primary endpoint are: _Cardiovascular (CV) death _Resuscitated cardiac arrest _Non-fatal MI _Non-fatal stroke | — |
Secondary
| Measure | Time frame |
|---|---|
| The key secondary endpoints of this study: Time to first occurrence of: _The composite of CV death, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, or hospitalization for ACS (with ECG abnormalities) requiring coronary revascularization _The composite of CV death, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, hospitalization for ACS (with ECG abnormalities), or unanticipated coronary revascularization _The composite of all cause death, resuscitated cardiac arrest, non-fatal MI, or non-fatal stroke Other secondary endpoints: Time to first occurrence of: _The composite of CV death, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, or hospitalization for new or worsening heart failure _The composite of CV death, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, hospitalization for ACS (with ECG abnormalities) requiring coronary revascularization, or hospitalization for new or worsening heart failure _The composite of all-cause death, resuscitated cardiac arrest, non-fatal MI, non-fatal stroke, or hospitalization for new or worsening heart failure _Fatal or non-fatal MI _All-cause death | — |
Countries
Netherlands
Outcome results
None listed