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

This study has been completed.

Sponsor:

Collaborator:

Bristol-Myers Squibb

Information provided by:

Sanofi

ClinicalTrials.gov Identifier:

NCT00335452

First received: June 8, 2006

Last updated: November 9, 2010

Last verified: November 2010

History of Changes

Results First Received: September 15, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Factorial Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Conditions:	Acute Coronary Disease Angina Unstable
Interventions:	Drug: Clopidogrel Drug: acetylsalicyclic acid (ASA)

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
25086 patients were enrolled and randomized between June 2006 and August 2009 in 597 sites in 39 countries. Because the observed overall blinded event rate was substantially lower than expected, the number of patients to be enrolled was increased from 18000 to 20000, then to 25000.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Treatment assignment was performed through an automated voice randomization service (AreS). At the same time, the AReS provided allocation to a Clopidogrel treatment regimen according to a pre-defined randomization list and to a ASA dose according to a factorial design.

Reporting Groups

	Description
Clopidogrel 300/75/75 mg + ASA Low Dose	Day 1: Clopidogrel 300 mg loading dose + ASA ≥ 300 mg Day 2 to Day 7: Clopidogrel 75 mg + ASA 75-100 mg Day 8 to Day 30: Clopidogrel 75 mg + ASA 75-100 mg
Clopidogrel 300/75/75 mg + ASA High Dose	Day 1: Clopidogrel 300 mg loading dose + ASA ≥ 300 mg Day 2 to Day 7: Clopidogrel 75 mg + ASA 300-325 mg Day 8 to Day 30: Clopidogrel 75 mg + ASA 300-325 mg
Clopidogrel 600/150/75 mg + ASA Low Dose	Day 1: Clopidogrel 600 mg loading dose + ASA ≥ 300 mg Day 2 to Day 7: Clopidogrel 150 mg + ASA 75-100 mg Day 8 to Day 30: Clopidogrel 75 mg + ASA 75-100 mg
Clopidogrel 600/150/75 mg + ASA High Dose	Day 1: Clopidogrel 600 mg loading dose + ASA ≥ 300 mg Day 2 to Day 7: Clopidogrel 150 mg + ASA 300-325 mg Day 8 to Day 30: Clopidogrel 75 mg + ASA 300-325 mg

Participant Flow: Overall Study

	Clopidogrel 300/75/75 mg + ASA Low Dose	Clopidogrel 300/75/75 mg + ASA High Dose	Clopidogrel 600/150/75 mg + ASA Low Dose	Clopidogrel 600/150/75 mg + ASA High Dose
STARTED	6312 ^[1]	6254 ^[1]	6267 ^[1]	6253 ^[1]
TREATED WITH CLOPIDOGREL	6271	6218	6228	6217
TREATED WITH ASA	6302	6251	6261	6247
COMPLETED	6154 ^[2]	6107 ^[2]	6108 ^[2]	6122 ^[2]
NOT COMPLETED	158	147	159	131
Death	156	144	158	129
Lost to Follow-up	2	3	1	2

[1]	Randomized
[2]	Completed 30 days follow-up period

Baseline Characteristics

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Reporting Groups

	Description
Clopidogrel 300/75/75 mg + ASA Low Dose	No text entered.
Clopidogrel 300/75/75 mg + ASA High Dose	No text entered.
Clopidogrel 600/150/75 mg + ASA Low Dose	No text entered.
Clopidogrel 600/150/75 mg + ASA High Dose	No text entered.
Total	Total of all reporting groups

Baseline Measures

	Clopidogrel 300/75/75 mg + ASA Low Dose	Clopidogrel 300/75/75 mg + ASA High Dose	Clopidogrel 600/150/75 mg + ASA Low Dose	Clopidogrel 600/150/75 mg + ASA High Dose	Total
Number of Participants [units: participants]	6312	6254	6267	6253	25086
Age [units: years] Mean ± Standard Deviation	61.3 ± 11.7	61.5 ± 11.7	61.2 ± 11.8	61.4 ± 11.9	61.3 ± 11.8
Age, Customized [units: participants]
< 65 years	3792	3740	3787	3735	15054
65 - 74 years	1573	1576	1543	1543	6235
≥ 75 years	947	937	937	975	3796
Missing	0	1	0	0	1
Gender [units: participants]
Female	1702	1756	1671	1742	6871
Male	4610	4498	4596	4511	18215
Region of Enrollment [units: participants]
Argentina	182	159	162	174	677
Australia	97	100	96	95	388
Austria	41	35	35	40	151
Belgium	55	61	59	53	228
Brazil	292	275	270	288	1125
Bulgaria	111	122	125	112	470
Canada	349	379	373	347	1448
Chile	95	85	82	90	352
China	510	492	500	515	2017
Croatia	114	145	144	114	517
Czech Republic	257	275	277	258	1067
Estonia	1	0	0	1	2
Finland	132	127	127	132	518
France	177	163	165	175	680
Germany	471	450	453	470	1844
Greece	20	21	23	21	85
India	658	650	645	646	2599
Ireland	24	13	15	23	75
Israel	286	272	275	282	1115
Italy	232	260	258	231	981
Korea, Republic of	161	149	152	165	627
Latvia	16	16	15	15	62
Lithuania	26	31	30	28	115
Malaysia	29	39	39	28	135
Mexico	16	17	19	17	69
Netherlands	46	48	48	46	188
New Zealand	36	31	29	29	125
Poland	365	322	325	362	1374
Romania	47	30	33	48	158
Russian Federation	132	137	138	131	538
Singapore	10	13	15	10	48
Slovakia	93	84	83	92	352
South Africa	24	14	14	23	75
Spain	264	276	283	263	1086
Sweden	10	11	9	10	40
Switzerland	51	64	64	48	227
Turkey	79	96	94	78	347
United Kingdom	28	29	34	28	119
United States	775	763	759	765	3062
Qualifying condition [units: participants]
Suspected Unstable Angina (UA)	1809	1771	1757	1877	7214
Suspected MI without ST elevation (NSTEMI)	2662	2662	2668	2539	10531
MI with ST elevation (STEMI)	1839	1817	1839	1832	7327
Missing	2	4	3	5	14
Intended PCI performed ^[1] [units: participants]
Yes	4377	4326	4262	4298	17263
No	1935	1928	2005	1955	7823

[1]	The intent to perform a PCI as early as possible and no later than 72 hours of randomization was part of the criteria for inclusion

Outcome Measures

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1. Primary:

First Occurrence of CV Death / MI / Stroke - Clopidogrel Treatment Regimen Comparison [ Time Frame: 30 days ]

Show Outcome Measure 1

2. Primary:

First Occurrence of CV Death / MI / Stroke - ASA Dose Comparison [ Time Frame: 30 days ]

Show Outcome Measure 2

3. Primary:

First Occurrence of CV Death / MI / Stroke - Interaction Clopidogrel Treatment Regimen and ASA Dose Level [ Time Frame: 30 days ]

Show Outcome Measure 3

4. Primary:

First Occurrence of CV Death / MI / Stroke - Clopidogrel Treatment Regimen Comparison in PCI Subgroup [ Time Frame: 30 days ]

Show Outcome Measure 4

5. Secondary:

Occurrence of Major Bleeding - Clopidogrel Dose Regimen Comparison [ Time Frame: 30 days ]

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Measure Type	Secondary
Measure Title	Occurrence of Major Bleeding - Clopidogrel Dose Regimen Comparison
Measure Description	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.
Time Frame	30 days
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis is on the intent-to-treat population (ITT) that consists of all patients randomized irrespective of whether they received study medication, underwent a PCI, or otherwise complied with the study protocol.

Reporting Groups

	Description
Clopidogrel 300/75/75 mg + ASA	Patients randomized to the Clopidogrel 300/75/75 mg dose regimen irrespective of the ASA dose
Clopidogrel 600/150/75 mg + ASA	Patients randomized to the Clopidogrel 600/150/75 mg dose regimen irrespective of the ASA dose.

Measured Values

	Clopidogrel 300/75/75 mg + ASA	Clopidogrel 600/150/75 mg + ASA
Number of Participants Analyzed [units: participants]	12566	12520
Occurrence of Major Bleeding - Clopidogrel Dose Regimen Comparison [units: participants]
Major bleeding	255	313
- Severe bleeding	195	236
- Major but not severe bleeding	65	83

Statistical Analysis 1 for Occurrence of Major Bleeding - Clopidogrel Dose Regimen Comparison

Groups ^[1]	All groups
Method ^[2]	Regression, Logistic
P Value ^[3]	0.012

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	logistic regression model including terms for ASA dose level (low or high) and qualifying condition (UA/NSTEMI or STEMI).
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	The a priori threshold for statistical significance is ≤0.05.

6. Secondary:

Occurrence of Major Bleeding - ASA Dose Level Comparison [ Time Frame: 30 days ]

Show Outcome Measure 6

7. Post-Hoc:

Occurrence of Stent Thrombosis - Clopidogrel Treatment Regimen Comparison [ Time Frame: 30 days ]

Show Outcome Measure 7

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Publication of the study is made jointly in the name of all wholehearted collaborators. Other papers are authored based on the contributions of the individuals to the overall study. Sub-studies with scientific merit which have received prior approvals of the Steering Committee may be published separately in the names of contributing Investigators. A copy of all manuscripts are provided to the Sponsors for their review and the final decision to publish is made by the Steering Committee.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Trial Information Transparency Team
Organization: sanofi-aventis
e-mail: GV-Contact-us@sanofi-aventis.com

Publications of Results:

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.

Fuster V. Fine-tuning therapy for acute coronary syndromes. N Engl J Med. 2010 Sep 2;363(10):976-7. 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; on behalf of the 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 Sep 1; [Epub ahead of print]

Stone GW. Acute coronary syndromes: finding meaning in OASIS 7. Lancet. 2010 Sep 1; [Epub ahead of print] No abstract available.

Publications automatically indexed to this study:

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. Epub 2008 Nov 1.

Responsible Party:	ICD, sanofi-aventis
ClinicalTrials.gov Identifier:	NCT00335452 History of Changes
Other Study ID Numbers:	EFC5965, EUDRACT: 2006-000313-38
Study First Received:	June 8, 2006
Results First Received:	September 15, 2010
Last Updated:	November 9, 2010
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

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