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

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.

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).

Study Overview

• Status: Completed
• Conditions: Acute Coronary Disease; Angina Unstable
• Intervention / Treatment: Drug: Clopidogrel; Drug: acetylsalicyclic acid (ASA)

• Study Type: Interventional
• Enrollment (Actual): 25086
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • Sanofi-Aventis Administrative Office
• Australia
  • Macquarie Park, Australia
    • sanofi-aventis Australia & New Zealand administrative office
• Austria
  • Vienna, Austria
    • Sanofi-Aventis Administrative Office
• Belgium
  • Diegem, Belgium
    • Sanofi-Aventis Administrative Office
• Brazil
  • Sao Paulo, Brazil
    • Sanofi-Aventis Administrative Office
• Bulgaria
  • Sofia, Bulgaria
    • Sanofi-Aventis Administrative Office
• Canada
  • Laval, Canada
    • Sanofi-Aventis Administrative Office
• Chile
  • Santiago de Chile, Chile
    • Sanofi-Aventis Administrative Office
• China
  • Beijing, China
    • Sanofi-Aventis Administrative Office
• Croatia
  • Zagreb, Croatia
    • Sanofi-Aventis Administrative Office
• Czech Republic
  • Praha, Czech Republic
    • Sanofi-Aventis Administrative Office
• Estonia
  • Tallinn, Estonia
    • Sanofi-Aventis Administrative Office
• Finland
  • Helsinki, Finland
    • Sanofi-Aventis Administrative Office
• France
  • Paris, France
    • Sanofi-Aventis Administrative Office
• Germany
  • Berlin, Germany
    • Sanofi-Aventis Administrative Office
• Greece
  • Athens, Greece
    • Sanofi-Aventis Administrative Office
• India
  • Mumbai, India
    • Sanofi-Aventis Administrative Office
• Ireland
  • Dublin, Ireland
    • Sanofi-Aventis Administrative Office
• Israel
  • Natanya, Israel
    • Sanofi-Aventis Administrative Office
• Italy
  • Milano, Italy
    • Sanofi-Aventis Administrative Office
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Sanofi-Aventis Administrative Office
• Latvia
  • Riga, Latvia
    • Sanofi-Aventis Administrative Office
• Lithuania
  • Vilnius, Lithuania
    • Sanofi-Aventis Administrative Office
• Malaysia
  • Kuala Lumpur, Malaysia
    • Sanofi-Aventis Administrative Office
• Mexico
  • Mexico, Mexico
    • Sanofi-Aventis Administrative Office
• Netherlands
  • Gouda, Netherlands
    • Sanofi-Aventis Administrative Office
• Poland
  • Warszawa, Poland
    • Sanofi-Aventis Administrative Office
• Romania
  • Bucuresti, Romania
    • Sanofi-Aventis Administrative Office
• Russian Federation
  • Moscow, Russian Federation
    • Sanofi-Aventis Administrative Office
• Singapore
  • Singapore, Singapore
    • Sanofi-Aventis Administrative Office
• Slovakia
  • Brastislava, Slovakia
    • Sanofi-Aventis Administrative Office
• South Africa
  • Midrand, South Africa
    • Sanofi-Aventis Administrative Office
• Spain
  • Madrid, Spain
    • Sanofi-Aventis Admnistrative Office
• Sweden
  • Bromma, Sweden
    • Sanofi-Aventis Administrative Office
• Switzerland
  • Geneva, Switzerland
    • Sanofi-Aventis Administrative Office
• Turkey
  • Istanbul, Turkey
    • Sanofi-Aventis Administrative Office
• United Kingdom
  • Surrey
    • Guildford, Surrey, United Kingdom
      • Sanofi-Aventis Administrative Office
• United States
  • New Jersey
    • Bridgewater, New Jersey, United States, 08807
      • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clopidogrel high dose treatment regimen + ASA high dose	Drug: Clopidogrel; oral administration; Other Names: Plavix; SR25990; Drug: acetylsalicyclic acid (ASA); oral administration
Experimental: Clopidogrel high dose treatment regimen + ASA low dose	Drug: Clopidogrel; oral administration; Other Names: Plavix; SR25990; Drug: acetylsalicyclic acid (ASA); oral administration
Active Comparator: Clopidogrel standard treatment regimen + ASA high dose	Drug: Clopidogrel; oral administration; Other Names: Plavix; SR25990; Drug: acetylsalicyclic acid (ASA); oral administration
Active Comparator: Clopidogrel standard treatment regimen + ASA low dose	Drug: Clopidogrel; oral administration; Other Names: Plavix; SR25990; Drug: acetylsalicyclic acid (ASA); oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First Occurrence of CV Death / MI / Stroke - Clopidogrel Treatment Regimen Comparison	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).	30 days
First Occurrence of CV Death / MI / Stroke - ASA Dose Comparison		30 days
First Occurrence of CV Death / MI / Stroke - Interaction Clopidogrel Treatment Regimen and ASA Dose Level		30 days
First Occurrence of CV Death / MI / Stroke - Clopidogrel Treatment Regimen Comparison in PCI Subgroup		30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Major Bleeding - Clopidogrel Dose Regimen Comparison	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.	30 days
Occurrence of Major Bleeding - ASA Dose Level Comparison		30 days

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Shamir MEHTA, MD, Hamilton General Hospital, McMaster University, CANADA

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: June 8, 2006
• First Submitted That Met QC Criteria: June 8, 2006
• First Posted (Estimate): June 9, 2006

Study Record Updates

• Last Update Posted (Estimate): November 18, 2010
• Last Update Submitted That Met QC Criteria: November 9, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: platelet aggregation inhibitors; acute coronary disease; percutaneous coronary
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: EFC5965; EUDRACT: 2006-000313-38