A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Escalation and Dose-Confirmation Study to Evaluate the Safety and Efficacy of Rivaroxaban in Combination with Aspirin Alone or with Aspirin and a Thienopyridine in Subjects with Acute Coronary Syndromes (39039039ACS2001)The ATLAS ACS TIMI 46 Trial (Anti-Xa Therapy to Lower cardiovascular events in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary Syndrome) - The ATLAS ACS TIMI 46 Trial

• Conditions: Acute Coronary Syndrome; MedDRA version: 8.1Level: LLTClassification code 10051592Term: Acute coronary syndrome

• Registration Number: EUCTR2006-004449-40-SE
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-12-22
• Last Update Posted: 12 June 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 6625

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:
- man or woman between 18 and 75 years of age, inclusive, for Stage 1. Subjects older than 75 years of age will be allowed to enroll in the 20-mg or lower total daily dose panels during Stage 1 assuming an acceptable safety profile is demonstrated, as determined by The Operations Committee in consultation with the IDMC Chair. For Stage 2, subjects over 75 years of age will be allowed to enroll assuming an acceptable safety profile is demonstrated in Stage 1.
- female subjects must be surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study; female subjects of childbearing potential must have a negative urine ß-hCG pregnancy test at screening.
- subjects must have signed an informed consent document.
- in countries where health authorities have approved the pharmacogenomic testing, subjects must have signed an informed consent for genetic testing indicating that they agree to participate in the genetic part of the study; participation in the genetic testing component is not mandatory for participation in the study.
- have symptoms suggestive of ACS that lasted at least 10 minutes at rest occurring within 7 days of randomization
- have either a diagnosis of STEMI or a diagnosis of NSTEMI or UA with at least 1 of the follow:
- elevated cardiac enzyme marker (e.g., CK-MB or troponin I or T)
- =1 mm ST-segment deviation (i.e., elevation or depression)
- TIMI risk score =3
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

Conditions that may increase the risk of bleeding:
- 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 the screening visit
- known pseudoaneurysm
- major surgery, biopsy of a parenchymal organ, eye surgery (including cataract surgery or vision correcting surgery), or serious trauma within 30 days before randomization
- clinically significant gastrointestinal bleeding within 6 months before the randomization visit
- have an 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

Conditions that may increase the risk of intracranial hemorrhage:
- history of hemorrhagic stroke at any time or clinical presentation consistent with intracranial hemorrhage (e.g., severe headache or new neurologic deficit after fibrinolytic therapy)
- recent ischemic stroke or transient ischemic attack (TIA) of any etiology within 30 days of randomization
- recent head trauma. (i.e., within 30 days of randomization)
- known intracranial neoplasm, arteriovenous malformation, or aneurysm
- sustained uncontrolled hypertension: systolic blood pressure of =180 mmHg or diastolic pressure of =100 mmHg that persists for more than 1 hour at time of screening despite treatment

Required drugs or procedures:
- the need for continued treatment with anticoagulant drugs (e.g., warfarin)
- systemic treatment with a strong inhibitor of cytochrome P450 3A4, such as ketoconazole or protease inhibitors, within 4 days before randomization or planned treatment during the time period of the study
- treatment with a strong inducer of cytochrome P450 3A4, such as rifampin/rifampicin within 4 days before randomization or planned treatment during the time period of the study
- planned PCI or peripheral arterial intervention

Severe concomitant diseases such as:
- cardiogenic shock
- refractory ventricular arrhythmias
- calculated creatinine clearance <30 mL/min at the screening visit
- known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis), or ALT >3 times the ULN
- anemia (i.e., hemoglobin <10 g/dL) at the screening visit
- have received transfusion of red blood cells (RBCs), whole blood, or platelets within 7 days before randomization
- known human immunodeficiency virus (HIV) infection at the screening visit
- substance abuse (drug or alcohol) problem within the previous 3 years
- have any severe condition that would limit life expectancy to less than 6 months

General:
- known allergy to aspirin
- known 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)
- have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment
- is pregnant or breast-feeding or planning to become pregnant during the study
- have previously completed or withdrawn from this study or any other study of rivaroxaban
- employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as fa

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified