Study of darapladib in the prevention of heart attacks, stroke and deathin patients who suffered a heart attack.
- Conditions
- after recent Acute Coronary Syndrome (ACS)MedDRA version: 14.1Level: PTClassification code 10051592Term: Acute coronary syndromeSystem Organ Class: 10007541 - Cardiac disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2009-012581-32-GB
- Lead Sponsor
- GlaxoSmithKline Research & Development, Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 13000
1. Signed written informed consent prior to beginning study-related procedures
2. Male or female aged at least 18 years, inclusive, at randomization. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator and in accordance with local practice in relation to adequate contraception. In Taiwan, subjects must be aged at least 20 years, inclusive, at randomization.
3. Hospitalisation for ACS (unstable angina, non-ST segment elevation MI, or ST segment elevation MI) =30 days prior to randomization:
a. Unstable angina (UA) is defined as ischemic chest discomfort (or equivalent) that occurs at rest with at least 1 episode lasting =10 minutes and is accompanied by new or presumably new ST segment deviation [transient (<20 minutes) elevation =0.1mV or dynamic horizontal/down-sloping depression =0.05mV)] in at least 2 contiguous leads without diagnostic biochemical changes in cardiac enzymes (serum troponin I or T, or creatine kinase-MB).
b. Non-ST segment elevation MI (NSTEMI) is defined as ischemic chest
discomfort (or equivalent) that occurs at rest with at least 1 episode lasting =10 minutes and is accompanied by a diagnostic elevation in cardiac biomarkers of myocardial injury (serum troponin I or T, or creatine kinase-MB ) above the upper limit of normal without persistent ST segment elevation.
c. ST segment elevation MI (STEMI) is defined as prolonged symptoms of
ischemic chest discomfort (or equivalent) at rest (with at least 1 episode lasting >20 min) and new or presumably new electrocardiographic changes (persistent ST segment elevation =0.1 mV in =2 contiguous precordial leads or =2 adjacent limb leads or new LBBB) that are accompanied by a diagnostic elevation in cardiac biomarkers (serum troponin I or T, or creatine kinase-MB) above the upper limit of normal.
4. All subjects must also have at least one of the following additional predictors of cardiovascular risk:
a. age =60 years at randomization.
b. history of documented MI prior to qualifying ACS event.
c. diabetes mellitus requiring pharmacotherapy.
d. significant renal dysfunction (defined as estimated glomerular filtration rate [eGFR] =30 and =59 mL/min per 1.73 m2).
e. polyvascular disease manifested in this ACS population as coexistent clinically diagnosed arterial disease in at least 1 peripheral arterial territory, defined as:
• cerebrovascular disease defined as carotid artery disease or as prior ischemic stroke that occured >3 months prior to randomization.
OR
• peripheral arterial disease (PAD)
5. The subject must be clinically stable for 24 hours prior to randomization (clinical stability is defined as the absence of chest pain, hemodynamic instability [e.g., hypotension, requirement for inotropic therapy], or significant arrhythmia [e.g., arrhythmia requiring treatment]).
6. For subjects in whom a PCI is planned as part of management for the qualifying ACS event, the subjects should undergo PCI prior to randomization whenever possible.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 6798
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6229
1. Clinical or laboratory manifestations of ACS (e.g., chest pain, ECG changes or increase in cardiac enzymes) that is not believed to be thrombotic in origin or is believed to be secondary to other apparent illness (e.g., sepsis, profound anemia, tachycardia, hypertensive emergency or decompensated heart failure).
2. Absence of obstructive coronary artery disease (i.e., at least one stenosis [>50%] in a major vessel, major branch or bypass graft) based on angiography, if performed, between the time of presentation with ACS and randomization.(NOTE: If all stenoses are successfully treated by PCI, the patient is still eligible.)
3. Planned coronary artery bypass graft (CABG) surgery or CABG surgery performed following the qualifying event and prior to randomization.
4. Cirrhosis, known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones), unstable liver disease (defined by the presence of any of the following felt by the investigator to be related to liver disease and not to other disease processes: ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), or evidence of abnormal liver function tests (total bilirubin or alkaline phosphatase >1.5 x upper limit of normal [ULN]; or alanine aminotransferase (ALT) >2.5 x ULN) or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
5. Severe renal impairment (e.g., patients with an eGFR <30 mL/min/1.73 m2 or receiving chronic dialysis) or history of nephrectomy or kidney transplant (regardless of renal function).
6. Current severe heart failure (New York Heart Association [NYHA] class III or IV).
7. Poorly controlled hypertension despite lifestyle modifications and
pharmacotherapy.
8. Any life-threatening condition with life expectancy <2 years, other than vascular disease, that might prevent the subject from completing the study.
9. Severe asthma that is poorly controlled on pharmacotherapy.
10. Positive pregnancy test (all female subjects of childbearing potential must have a urine or serum ß-human chorionic gonadotropin [hCG] pregnancy test performed within 7 days prior to randomization) or is known to be pregnant or lactating.
11. History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions, or severe allergic responses.
12. Alcohol or drug abuse within the past 6 months. Current mental condition (psychiatric disorder, senility or dementia), which may affect study compliance or prevent understanding of the aims, investigational procedures or possible consequences of the study.
13. Current or planned chronic administration of strong oral or injectable cytochrome P- 450 isoenzyme 3A4 (CYP3A4) inhibitors.
14. Subjects with 2 known birth parents of at least 50% Japanese, Chinese, or Korean ancestry (or if unknown, a reasonable likelihood of such ancestry) must have a blood sample collected for assessment of Lp-PLA2 activity by the central laboratory prior to randomization. Those with Lp-PLA2 activity =20.0nmol/min/mL will be excluded from participation in the study.
15. Previous exposure to darapladib (SB-480848).
16. Use of another investigational product within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of darapladib or matching placebo.
17. Currently in a study of an investigational device.
18. Any other reason the investigator deems the subject to be unsuitable
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method