Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS (CURRENT/OASIS7)

• ClinicalTrials.gov Identifier: NCT00335452
• Recruitment Status: Completed
• First Posted: June 9, 2006
• Results First Posted: October 7, 2010
• Last Update Posted: November 18, 2010
• Sponsor: Sanofi
• Collaborator: Bristol-Myers Squibb
• Information provided by: Sanofi

Tracking Information

• First Submitted Date: June 8, 2006
• First Posted Date: June 9, 2006
• Results First Submitted Date: September 15, 2010
• Results First Posted Date: October 7, 2010
• Last Update Posted Date: November 18, 2010
• Study Start Date: June 2006
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 15, 2010)

• First Occurrence of CV Death / MI / Stroke - Clopidogrel Treatment Regimen Comparison [ Time Frame: 30 days ]
  The primary endpoint is the first occurrence of any of the following events:

  • Cardiovascular death (any death with a clear cardiovascular or unknown cause),
  • Myocardial Infarction (diagnosis of new Myocardial Infarction (MI) - nonfatal or fatal)
  • Stroke (presence of a new focal neurologic deficit thought to be vascular in origin, with signs or symptoms lasting more than 24 hours - nonfatal or fatal)

  reported between the randomization and Day 30 (inclusive), and validated by the blinded Event Adjudication Committee (EAC).
• First Occurrence of CV Death / MI / Stroke - ASA Dose Comparison [ Time Frame: 30 days ]
• First Occurrence of CV Death / MI / Stroke - Interaction Clopidogrel Treatment Regimen and ASA Dose Level [ Time Frame: 30 days ]
• First Occurrence of CV Death / MI / Stroke - Clopidogrel Treatment Regimen Comparison in PCI Subgroup [ Time Frame: 30 days ]

• Original Primary Outcome Measures (submitted: June 8, 2006): At Day 30 , first occurrence of cardiovascular death, myocardial infarction and stroke; second co-primary outcome: first occurrence of cardiovascular death, stroke, myocardial infarction and recurrent ischemia

Current Secondary Outcome Measures (submitted: November 9, 2010)

• Occurrence of Major Bleeding - Clopidogrel Dose Regimen Comparison [ Time Frame: 30 days ]
  Major bleeding is defined as any severe bleeding (associated with any of the following: death, leading to a drop in hemoglobin ≥ 5 g/dl, significant hypotension with the need for inotropic agents, symptomatic intracranial hemorrhage, requirement for surgery or for a transfusion ≥ 4 units of red blood cells or equivalent whole blood) and other major bleeding (significantly disabling bleeding, or intraocular bleeding leading to significant loss of vision or bleeding requiring transfusion of 2-3 units of red blood cells or equivalent whole blood) after validation by the independent EAC.
• Occurrence of Major Bleeding - ASA Dose Level Comparison [ Time Frame: 30 days ]

• Original Secondary Outcome Measures (submitted: June 8, 2006): At Day 30, rate of major bleeding
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS
• Official Title: Randomized, Multinational, Double-blind Study, Comparing a High Loading Dose Regimen of Clopidogrel Versus Standard Dose in Patients With Unstable Angina or Myocardial Infarction Managed With an Early Invasive Strategy.
• Brief Summary: The purpose of this study is to evaluate whether a higher dosage of clopidogrel with aspirin (two doses) will decrease the risk of ischemic complications (cardiac death (CV death), myocardial infarction (MI), stroke) after a percutaneous coronary intervention (PCI).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Acute Coronary Disease
• Angina Unstable

Intervention

• Drug: Clopidogrel
  oral administration
  Other Names:

  • SR25990
  • Plavix
• Drug: acetylsalicyclic acid (ASA)
  oral administration

Study Arms

• Experimental: Clopidogrel high dose treatment regimen + ASA high dose
  Interventions:

  • Drug: Clopidogrel
  • Drug: acetylsalicyclic acid (ASA)
• Experimental: Clopidogrel high dose treatment regimen + ASA low dose
  Interventions:

  • Drug: Clopidogrel
  • Drug: acetylsalicyclic acid (ASA)
• Active Comparator: Clopidogrel standard treatment regimen + ASA high dose
  Interventions:

  • Drug: Clopidogrel
  • Drug: acetylsalicyclic acid (ASA)
• Active Comparator: Clopidogrel standard treatment regimen + ASA low dose
  Interventions:

  • Drug: Clopidogrel
  • Drug: acetylsalicyclic acid (ASA)

Publications *

• CURRENT-OASIS 7 Investigators; Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Eikelboom JW, Fox KA, Granger CB, Jolly S, Joyner CD, Rupprecht HJ, Widimsky P, Afzal R, Pogue J, Yusuf S. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010 Sep 2;363(10):930-42. doi: 10.1056/NEJMoa0909475. Erratum In: N Engl J Med. 2010 Oct 14;363(16):1585.
• Fuster V. Fine-tuning therapy for acute coronary syndromes. N Engl J Med. 2010 Sep 2;363(10):976-7. doi: 10.1056/NEJMe1008891. No abstract available.
• Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, Faxon DP, Rupprecht HJ, Budaj A, Avezum A, Widimsky P, Steg PG, Bassand JP, Montalescot G, Macaya C, Di Pasquale G, Niemela K, Ajani AE, White HD, Chrolavicius S, Gao P, Fox KA, Yusuf S; CURRENT-OASIS 7 trial investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010 Oct 9;376(9748):1233-43. doi: 10.1016/S0140-6736(10)61088-4.
• Stone GW. Acute coronary syndromes: finding meaning in OASIS 7. Lancet. 2010 Oct 9;376(9748):1203-5. doi: 10.1016/S0140-6736(10)61262-7. No abstract available.
• Bossard M, Gao P, Boden W, Steg G, Tanguay JF, Joyner C, Granger CB, Kastrati A, Faxon D, Budaj A, Pais P, Di Pasquale G, Valentin V, Flather M, Moccetti T, Yusuf S, Mehta SR. Antiplatelet therapy in patients with myocardial infarction without obstructive coronary artery disease. Heart. 2021 Nov;107(21):1739-1747. doi: 10.1136/heartjnl-2020-318045. Epub 2021 Jan 27.
• Bossard M, Granger CB, Tanguay JF, Montalescot G, Faxon DP, Jolly SS, Widimsky P, Niemela K, Steg PG, Natarajan MK, Gao P, Fox KAA, Yusuf S, Mehta SR. Double-Dose Versus Standard-Dose Clopidogrel According to Smoking Status Among Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention. J Am Heart Assoc. 2017 Nov 3;6(11):e006577. doi: 10.1161/JAHA.117.006577.
• Mehta SR, Bassand JP, Chrolavicius S, Diaz R, Fox KA, Granger CB, Jolly S, Rupprecht HJ, Widimsky P, Yusuf S; CURRENT-OASIS 7 Steering Committee. Design and rationale of CURRENT-OASIS 7: a randomized, 2 x 2 factorial trial evaluating optimal dosing strategies for clopidogrel and aspirin in patients with ST and non-ST-elevation acute coronary syndromes managed with an early invasive strategy. Am Heart J. 2008 Dec;156(6):1080-1088.e1. doi: 10.1016/j.ahj.2008.07.026. Epub 2008 Nov 1.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 12, 2010): 25086
• Original Enrollment (submitted: June 8, 2006): 14000
• Actual Study Completion Date: September 2009
• Actual Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosed with acute coronary disease with clinical symptoms and at least electrocardiogram changes or cardiac enzymes elevated

Exclusion Criteria:

• Use of anticoagulants within 10 days with an international normalized ratio (INR) > 1.5 or planned use during the hospitalisation period
• Administration of clopidogrel > 75 mg prior to randomization
• Contraindication to clopidogrel or aspirin
• Active bleeding or significant risk of bleeding

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Croatia, Czech Republic, Estonia, Finland, France, Germany, Greece, India, Ireland, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Poland, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Turkey, United Kingdom, United States
• Removed Location Countries: Denmark, Hungary, Norway, Philippines

Administrative Information

• NCT Number: NCT00335452
• Other Study ID Numbers: EFC5965; EUDRACT: 2006-000313-38
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: ICD, sanofi-aventis
• Original Responsible Party: Not Provided
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Bristol-Myers Squibb

Investigators

• Principal Investigator: Shamir MEHTA, MD; Hamilton General Hospital, McMaster University, CANADA

• PRS Account: Sanofi
• Verification Date: November 2010