Rivaroxaban in Combination With Aspirin Alone or With Aspirin and a Thienopyridine in Patients With Acute Coronary Syndromes (The ATLAS ACS TIMI 46 Trial)

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00402597
First received: November 21, 2006
Last updated: September 28, 2012
Last verified: September 2012
  Purpose

The purpose of this study is to evaluate the safety of rivaroxaban in patients with recent acute coronary syndrome (ACS) and to assess the ability of rivaroxaban to reduce the occurrence of death, myocardial infarction (heart attack), repeat myocardial infarctions, stroke, and ischemia (inadequate blood supply to a local area) in patients with recent ACS.


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Rivaroxaban/Placebo
Drug: Placebo
Drug: Rivaroxaban
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Thrombolysis in Myocardial Infarction (TIMI) Clinically Significant Bleeding Events (Primary Safety) [ Time Frame: Day 1 to Day 210 ] [ Designated as safety issue: Yes ]
    The number of patients with a first occurrence of a TIMI clinically significant bleeding event that occurred from the time of randomization to the time of the last patient contact. TIMI clinically significant bleeding events included TIMI minor bleeding events, TIMI major bleeding events, or any bleeding that required medical attention.

  • The Composite Endpoint of All Cause Death, Myocardial Infarction (MI) (Including Repeat MI), Stroke (Ischemic, Hemorrhagic or Unknown), or Severe Recurrent Ischemia Requiring Revascularization (Primary Efficacy) [ Time Frame: Day 1 to Day 210 ] [ Designated as safety issue: No ]
    The number of patients who died due to any cause or had a first occurrence of MI (including repeat MI) or stroke (ischemic, hemorrhagic or unknown) or severe recurrent ischemia requiring revascularization from the time of randomization to the last date of patient contact.


Secondary Outcome Measures:
  • The Composite Endpoint of Death (All Cause), Myocardial Infarction (MI) (or Repeat MI), or Stroke [ Time Frame: Day 1 to Day 210 ] [ Designated as safety issue: No ]
    The number of patients who died due to any cause or had a first occurrence of MI (or repeat MI) or stroke from the time of randomization to the last date of patient contact.

  • The Composite Endpoint of Cardiovascular Death, Myocardial Infarction (MI), or Stroke [ Time Frame: Day 1 to Day 210 ] [ Designated as safety issue: No ]
    The number of patients with the composite endpoint of cardiovascular death or MI or stroke that occurred from the time of randomization to the last date of patient contact.

  • The Number of Deaths (All Cause) [ Time Frame: Day 1 to Day 210 ] [ Designated as safety issue: No ]
    The number of patients who died due to any cause from the time of randomization to the last date of patient contact.

  • The Composite Endpoint of Death (All Cause), MI (or reMI), Stroke, Severe Recurrent Ischemia Requiring Revascularization, or Thrombolysis in Myocardial Infarction (TIMI) (Major or Minor Bleeding) to Assess the Net Clinical Benefit [ Time Frame: Day 1 to Day 210 ] [ Designated as safety issue: No ]
    The number of patients who died due to any cause or had a first occurrence of MI (or repeat MI), or stroke, or severe recurrent ischemia requiring revascularization, or TIMI (major or minor bleeding) from the time of randomization to the last date of patient contact to assess the net clinical benefit of rivaroxaban.


Enrollment: 3490
Study Start Date: November 2006
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 001
Rivaroxaban 1 rivaroxaban tablet twice daily for 6 months. Safety at each dose level will be confirmed before additional patients are randomized to the next higher dose level.
Drug: Rivaroxaban
1 rivaroxaban tablet twice daily for 6 months. Safety at each dose level will be confirmed before additional patients are randomized to the next higher dose level.
Experimental: 002
Rivaroxaban/Placebo 1 rivaroxaban tablet once daily (and 1 placebo tablet once daily) for 6 months. Safety at each dose level will be confirmed before additional patients are randomized to the next higher dose level.
Drug: Rivaroxaban/Placebo
1 rivaroxaban tablet once daily (and 1 placebo tablet once daily) for 6 months. Safety at each dose level will be confirmed before additional patients are randomized to the next higher dose level.
Placebo Comparator: 003
Placebo 1 placebo tablet twice daily for 6 months.
Drug: Placebo
1 placebo tablet twice daily for 6 months.

Detailed Description:

This is a randomized (patients will be assigned to study treatment by chance), double-blind (neither the patient nor the study doctor will know the identity of the assigned study treatment) study to evaluate the safety and efficacy of rivaroxaban (study drug) compared to placebo (a tablet identical in appearance to study drug but contains no active drug) in patients with acute coronary syndrome (ACS [a condition where blood flow in a blood vessel in the heart is restricted because of a blood clot]). Rivaroxaban is a drug that acts as a blood thinner and is being tested to see if it will be safe and effective in patients diagnosed ACS. The goal of this study is to identify the dose and dosing schedule (once-a-day or twice-a-day dosing) of rivaroxaban that will be safe and effective in preventing adverse cardiovascular outcomes such as death, myocardial infarctions (MI) including repeat myocardial infarction (reMI), stroke, or ischemia (inadequate blood supply to a local area) requiring revascularization (ie, the re-establishment of blood supply to a part or an organ) in patients with ACS who are receiving antiplatelet therapy (ie, aspirin alone or aspirin plus an approved thienopyridine, a type of drug such as clopidogrel that acts to inhibit the formation of blood clots). Approximately 3500 patients are planned to participate in the study for approximately 7 months. At study entry, all patients who are currently receiving treatment for ACS with antiplatelet therapy will be permitted to continue this therapy during the study. Patients will be enrolled and randomized to receive placebo, rivaroxaban administered as a once-daily dose, or rivaroxaban administered as a twice-daily dose at each dose level of rivaroxaban tested. Patients randomized at each dose level will continue to receive the same treatment for 6 months. Near the end of enrollment at the first dose level, available safety and efficacy data from patients will be assessed by an Operations Committee before enrolling and randomizing additional patients to the next higher dose level of rivaroxaban. Increasing dose levels of rivaroxaban are planned; however, progression to each higher dose level will be at the discretion of the Operations Committee. Patient safety will be monitored by evaluating adverse events reported, results from clinical laboratory tests, findings from electrocardiograms (ECGs) and vital signs measurements, findings from physical examinations, and the number of patients with protocol-defined major or minor bleeding, or bleeding requiring medical attention. All patients will take study drug or placebo tablets orally (by mouth) twice daily for 6 months starting at an initial total daily dose of 5 mg. Both once- and twice-daily dosing regimens will be tested at each rivaroxaban dose level planned.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have symptoms suggestive of ACS that lasted at least 10 minutes at rest occurring within 7 days of randomization
  • Have a diagnosis of ST-elevation myocardial infarction or non-ST elevation myocardial infarction/unstable angina (ie, chest pain or discomfort) (ST elevation is an abnormal finding from an ECG test) with at least 1 protocol-defined high risk feature

Exclusion Criteria:

  • Active bleeding or high risk of bleeding or intracranial hemorrhage (bleeding within the skull enclosing the brain)
  • Need for continued anticoagulant therapy
  • Significantly impaired renal (kidney) or hepatic (liver) function
  • Severe concomitant diseases such as cardiogenic shock (heart damage that results in insufficient blood supply to other parts or organs of the body), refractory ventricular arrhythmias (irregular contractions of the heart unresponsive to treatment), or any severe condition that would limit life expectancy of the patient to less than 6 months
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00402597

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Bayer
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
Publications:
Responsible Party: VP FRANCHISE MED LDR, Johnson & Johnson Pharmaceutical Research and Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00402597     History of Changes
Obsolete Identifiers: NCT01151332
Other Study ID Numbers: CR013417, 39039039ACS2001
Study First Received: November 21, 2006
Results First Received: July 25, 2012
Last Updated: September 28, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Acute Coronary Syndrome (ACS)
Myocardial Ischemia
Rivaroxaban (BAY59-7939)
Anti-platelet agents
Aspirin
Thienopyridine
Clopidogrel

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Aspirin
Rivaroxaban
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics

ClinicalTrials.gov processed this record on August 28, 2014