A Randomized, Double-Blind, Placebo-Controlled, Event-Driven Multicenter Study to Evaluate the Efficacy and Safety of Rivaroxaban in Subjects with a Recent Acute Coronary SyndromeThe ATLAS ACS 2 TIMI 51 Trial (The second trial of Anti-Xa Therapy to Lower cardiovascular events in Addition to standard therapy in Subjects with Acute Coronary Syndrome)Amendment INT-2 - The ATLAS ACS 2 TIMI 51 Trial

Conditions: Acute Coronary Syndrome (ACS)
MedDRA version: 14.0Level: PTClassification code 10051592Term: Acute coronary syndromeSystem Organ Class: 10007541 - Cardiac disorders

Registration Number: EUCTR2008-002708-25-DE

Lead Sponsor: Janssen-Cilag International N.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 16000

Inclusion Criteria

Potential subjects must satisfy the following criteria to be enrolled in the study:
• Man or woman 18 years of age or older
• Currently receiving ASA therapy (75 to 100 mg/day) alone or in combination with a thienopyridine (clopidogrel
or ticlopidine per national dosing recommendation)
• Have been hospitalized for symptoms suggestive of ACS that lasted at least 10 minutes at rest, and occurred 48
hours or less before hospital presentation or who develop ACS while being hospitalized for an indication other
than ACS, and have a diagnosis of:
- STEMI:
- elevation of ST-segment more than 0.1 millivolt (mV) in 2 or more continuous ECG leads, or new left bundle
branch block, or ST segment depression 0.1 mV or greater in 2 of the precordial leads V1 V4 with evidence
suggestive of true posterior infarction, all with elevated biomarkers of myocardial necrosis (creatinine kinase
muscle and brain isoenzyme [CK-MB] or troponin)
- NSTEMI:
- Elevated biomarkers of myocardial necrosis (creatinine kinase-muscle and brain isoenzyme [CK-MB] or
troponin) plus 1 of the following:
- Transient ST-segment elevation, or ST-segment depression, or T-wave changes consistent with myocardial
ischemia
or
- Identification of a culprit lesion at coronary angiography demonstrating recent, active intracoronary athero
thrombosis (for example, thrombus or an ulcerated plaque
- UA with at least 1 of the following:
- transient or persistent ST-segment deviation 0.1 mV or greater in 1 or more ECG leads OR
- TIMI risk score of =4
• Subjects who are 18 to 54 years of age inclusive must also have either diabetes mellitus or a prior MI in addition
to the presenting ACS event.
• Women must be:
– postmenopausal (for at least 2 years), or
– surgically sterile, (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be
incapable of pregnancy), or
– abstinent (at the discretion of the investigator/per local regulations), or
– if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives,
contraceptive injections, contraceptive patch, intrauterine device, double-barrier method, male partner
sterilization) as local regulations permit, before entry, and must agree to continue to use the same method of
contraception throughout the study.
• Women of childbearing potential must have a negative urine ß-human chorionic gonadotropin (ß-hCG)
pregnancy test at screening. Serum pregnancy testing may be performed if required by local regulation.
• Subjects must have signed an informed consent document indicating that they understand the purpose of and
procedures required for the study and are willing to participate in the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Bleeding risk
• Any condition that, in the opinion of the investigator, contraindicates anticoagulant therapy or would have an
unacceptable risk of bleeding, such as, but not limited to, the following:
– active internal bleeding, clinically significant bleeding, bleeding at a noncompressible site, or bleeding diathesis
within 30 days of randomization
– platelet count <90,000/µL at screening
– history of intracranial hemorrhage
– major surgery, biopsy of a parenchymal organ, or serious trauma within 30 days before randomization
– clinically significant gastrointestinal bleeding within 12 months before randomization
– have an International Normalized Ratio (INR) known to be >1.5 at the time of screening
– abciximab bolus or infusion within the past 8 hours, or an eptifibatide or tirofiban bolus or infusion within the
past 2 hours before randomization
– any other condition known to increase the risk of bleeding
Severe concomitant diseases such as:
• Cardiogenic shock at the time of randomization
• Ventricular arrhythmias refractory to treatment at the time of randomization
• Calculated creatinine clearance <30 mL/min at screening
• Known significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis), or liver function test
(LFT) abnormalities (confirmed with repeat testing) which would require study drug discontinuation, i.e., ALT
>5 x ULN or ALT >3 x ULN plus total bilirubin >2 x ULN
• A prior ischemic stroke or TIA in subjects who are planned to be included in stratum 2 (ASA plus
thienopyridine). (Note: Subjects with a prior ischemic stroke or TIA are eligible for inclusion in the study
only if they are intended to be treated with ASA only). Subjects with a prior hemorrhagic stroke are excluded
completely from the study.
• Anemia (i.e., hemoglobin <10 g/dL) at screening
• Known clinical history of HIV infection at screening
• Substance abuse (drug or alcohol) problem within the previous 6 months
• Any severe condition that would limit life expectancy to less than 6 months
General:
• Systemic treatment with strong CYP 3A4 and P-gp inhibitors (e.g., certain azoleantimycotics, such as
ketoconazole and HIV protease inhibitors, such as ritonavir). These active substances are strong inhibitors of
both CYP3A4 and P-gp.
•Allergy or hypersensitivity to any component of rivaroxaban or placebo excipients (includes lactose,
microcrystalline cellulose, magnesium stearate, hypromellose, macrogol, croscarmellose sodium, sodium lauryl
sulfate, titanium oxide)
• Known aspirin allergy
• Atrial fibrillation excluded except for subjects younger than 60 years of age who have no clinical or
echocardiographic evidence of cardiopulmonary disease and who had only a single episode of atrial fibrillation
that occurred more than 2 years ago.
•Other conditions requiring long-term anticoagulation
• Use of disallowed therapies (see Section 8, Prestudy and Concomitant Therapy)
• Received an investigational drug or used an investigational medical device within 30 days before the planned
start of treatment, or are currently enrolled in an investigational study
• Anticipated need for chronic (more than 4 weeks) therapy with non steroidal anti-inflammatory drugs (NSAIDs)
• Is pregnant or breast-feeding or planning to become pregnant during the study
• Have previously completed or withdrawn from this study
• Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the
study or prevent the subject from