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

NCT00402597 | Completed Phase 2 Results

• 2 other identifiers: CR01341739039039ACS2001
• Study Type: interventional
• Target: 3,490
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Acute Coronary Syndrome

Keywords

Acute Coronary Syndrome (ACS); Myocardial Ischemia; Rivaroxaban (BAY59-7939); Anti-platelet agents; Aspirin; Thienopyridine; Clopidogrel

Outcome Measures

Primary Outcomes (2)

• Thrombolysis in Myocardial Infarction (TIMI) Clinically Significant Bleeding Events (Primary Safety)

  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.

  Day 1 to Day 210

• 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)

  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.

  Day 1 to Day 210

Secondary Outcomes (4)

• The Composite Endpoint of Death (All Cause), Myocardial Infarction (MI) (or Repeat MI), or Stroke

  Day 1 to Day 210

• The Composite Endpoint of Cardiovascular Death, Myocardial Infarction (MI), or Stroke

  Day 1 to Day 210

• The Number of Deaths (All Cause)

  Day 1 to Day 210

• 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

  Day 1 to Day 210

Study Arms (3)

001

EXPERIMENTAL

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

002

EXPERIMENTAL

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

003

PLACEBO COMPARATOR

Placebo 1 placebo tablet twice daily for 6 months.

Drug: Placebo

Interventions

Rivaroxaban/Placebo DRUG

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.

002

Placebo DRUG

1 placebo tablet twice daily for 6 months.

003

Rivaroxaban DRUG

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.

001

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: lead
• Bayer: collaborator

Related Publications (3)

• Mega JL, Braunwald E, Mohanavelu S, Burton P, Poulter R, Misselwitz F, Hricak V, Barnathan ES, Bordes P, Witkowski A, Markov V, Oppenheimer L, Gibson CM; ATLAS ACS-TIMI 46 study group. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet. 2009 Jul 4;374(9683):29-38. doi: 10.1016/S0140-6736(09)60738-8. Epub 2009 Jun 17.

  PMID: 19539361 RESULT

• Gibson WJ, Nafee T, Travis R, Yee M, Kerneis M, Ohman M, Gibson CM. Machine learning versus traditional risk stratification methods in acute coronary syndrome: a pooled randomized clinical trial analysis. J Thromb Thrombolysis. 2020 Jan;49(1):1-9. doi: 10.1007/s11239-019-01940-8.

  PMID: 31535314 DERIVED

• Gibson CM, Mega JL, Burton P, Goto S, Verheugt F, Bode C, Plotnikov A, Sun X, Cook-Bruns N, Braunwald E. Rationale and design of the Anti-Xa therapy to lower cardiovascular events in addition to standard therapy in subjects with acute coronary syndrome-thrombolysis in myocardial infarction 51 (ATLAS-ACS 2 TIMI 51) trial: a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rivaroxaban in subjects with acute coronary syndrome. Am Heart J. 2011 May;161(5):815-821.e6. doi: 10.1016/j.ahj.2011.01.026.

  PMID: 21570509 DERIVED

Related Links

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

MeSH Terms

Conditions

Acute Coronary Syndrome; Myocardial Ischemia

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: VP FRANCHISE MED LDR
• Organization: Johnson & Johnson Pharmaceutical Research and Development, L.L.C.

1 908 927 7767

Study Officials

• Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial

  Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: November 21, 2006
• First Posted: November 22, 2006
• Study Start: November 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: October 4, 2012
• Results First Posted: August 29, 2012

Record last verified: 2012-09