NCT02293395

Brief Summary

The purpose of this study is to estimate the risk of bleeding with rivaroxaban, compared with acetylsalicylic acid (ASA), in addition to a single antiplatelet/ platelet adenosine diphosphate P2Y12 receptor antagonist (P2Y12 inhibitor agent: clopidogrel or ticagrelor), in participants with a recent acute coronary syndrome (ACS: including ST segment elevation myocardial infarction \[STEMI\] and non-ST-segment elevation acute coronary syndrome \[NSTE-ACS\]).

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
3,037

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2015

Shorter than P25 for phase_2

Geographic Reach
20 countries

259 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 13, 2014

Completed
5 days until next milestone

First Posted

Study publicly available on registry

November 18, 2014

Completed
5 months until next milestone

Study Start

First participant enrolled

April 20, 2015

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 14, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 14, 2016

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

November 13, 2017

Completed
Last Updated

December 26, 2017

Status Verified

November 1, 2017

Enrollment Period

1.5 years

First QC Date

November 13, 2014

Results QC Date

October 11, 2017

Last Update Submit

November 30, 2017

Conditions

Keywords

Acute Coronary SyndromeMyocardial infarctionUnstable anginaAcetylsalicylic acidRivaroxabanJNJ-39039039Bay 59-7939XareltoClopidogrelTicagrelorPlavixBrilintaEffient

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Non Coronary Artery Bypass Graft-Related (Non CABG-related) Thrombolysis in Myocardial Infarction (TIMI) Clinically Significant Bleeding Events

    Non CABG-related TIMI clinically significant bleeding events are sum of non CABG-related TIMI major bleeding events, TIMI minor bleeding events and TIMI bleeding events requiring medical attention. Major: any symptomatic intracranial bleeding: clinically overt signs of hemorrhage with hemoglobin (Hb) drop of greater than or equal to (\>=)5 gram per deciliter (g/dl) (or absolute drop in hematocrit of \>=15%) and fatal bleeding (results in death within 7 days); Minor: clinically overt sign of hemorrhage with Hb drop of 3 - \<5 g/dl (or drop in hematocrit of 9 - \<15%); requiring medical attention: bleeding event that required medical, surgical treatment/laboratory evaluation and did not meet criteria for major/minor bleeding event.

    From start of study treatment until follow-up (up to 390 days)

Study Arms (4)

Stratum 1/ASA

ACTIVE COMPARATOR

Acetylsalicylic acid (ASA) 100 milligram (mg) enteric-coated tablet once daily orally along with clopidogrel 75 mg once daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier.

Drug: Acetylsalicylic acidDrug: Clopidogrel

Stratum 1/Rivaroxaban

EXPERIMENTAL

Rivaroxaban 2.5 mg tablet twice daily orally along with clopidogrel 75 mg once daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier.

Drug: RivaroxabanDrug: Clopidogrel

Stratum 2/ASA

ACTIVE COMPARATOR

ASA 100 mg enteric-coated tablet once daily orally along with ticagrelor 90 mg twice daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier.

Drug: Acetylsalicylic acidDrug: Ticagrelor

Stratum 2/Rivaroxaban

EXPERIMENTAL

Rivaroxaban 2.5 mg tablet twice daily orally along with ticagrelor 90 mg twice daily orally, up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier.

Drug: RivaroxabanDrug: Ticagrelor

Interventions

ASA 100 mg enteric-coated tablet once daily orally.

Also known as: Aspirin
Stratum 1/ASAStratum 2/ASA

Rivaroxaban 2.5 mg tablet twice daily orally.

Also known as: JNJ-39039039, Bay 59-7939, Xarelto
Stratum 1/RivaroxabanStratum 2/Rivaroxaban

Clopidogrel 75 mg once daily orally.

Also known as: Plavix
Stratum 1/ASAStratum 1/Rivaroxaban

Ticagrelor 90 mg twice daily orally.

Also known as: Brilinta
Stratum 2/ASAStratum 2/Rivaroxaban

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants, 18 years or older, must have symptoms suggestive of acute coronary syndrome (ACS) (angina, or symptoms thought to be equivalent) within 48 hours of hospital presentation, or developed ACS while being hospitalized, and has a diagnosis of: a) ST segment elevation myocardial infarction (STEMI); b) non-ST-segment elevation acute coronary syndrome (NSTE-ACS). However, participant who is 54 years of age or younger must also have either diabetes mellitus or a history of a prior myocardial infarction (MI), in addition to the presenting ACS event
  • Participant must be randomized within the screening window of 10 days after hospital admission for the index ACS event. Participant should have received acute phase treatment for the index ACS, such as intravenous anticoagulant or antiplatelet, and are receiving maintenance dual antiplatelet therapy (DAPT) with either clopidogrel plus acetyl salicylic acid (ASA), or ticagrelor plus ASA, with the intent to continue the treatment with a platelet adenosine diphosphate P2Y12 receptor antagonist (P2Y12 inhibitor) after randomization
  • Participants must agree to provide a pharmacogenomics deoxyribonucleic acid (DNA) sample

You may not qualify if:

  • Participant has any conditions that, in the opinion of the investigator, contraindicates anticoagulant therapy or would have an unacceptable risk
  • Participant with a prior stroke of any etiology or transient ischemic attack (TIA)
  • Participant who received thrombolytic therapy as treatment for the index ACS event cannot be enrolled in the ticagrelor stratum
  • Participant has anticipated need for chronic administration of omeprazole or esomeprazole concomitantly with clopidogrel
  • Participant has known allergy or intolerance to ASA or rivaroxaban

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (259)

Unknown Facility

Alexander City, Alabama, United States

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Banning, California, United States

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Sylmar, California, United States

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Aurora, Colorado, United States

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Littleton, Colorado, United States

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Jupiter, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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Pensacola, Florida, United States

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Tampa, Florida, United States

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Athens, Georgia, United States

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Cumming, Georgia, United States

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Macon, Georgia, United States

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Tucker, Georgia, United States

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Boise, Idaho, United States

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Coeur d'Alene, Idaho, United States

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Jerseyville, Illinois, United States

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Indianapolis, Indiana, United States

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Munster, Indiana, United States

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Bay City, Michigan, United States

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Kalamazoo, Michigan, United States

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Lansing, Michigan, United States

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Mount Clemens, Michigan, United States

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Ypsilanti, Michigan, United States

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Minneapolis, Minnesota, United States

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Columbia, Missouri, United States

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St Louis, Missouri, United States

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Kalispell, Montana, United States

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Stony Brook, New York, United States

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Rocky Mount, North Carolina, United States

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Sanford, North Carolina, United States

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Cincinnati, Ohio, United States

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Zanesville, Ohio, United States

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Bartlesville, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Abington, Pennsylvania, United States

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Langhorne, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Sayre, Pennsylvania, United States

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York, Pennsylvania, United States

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Rapid City, South Dakota, United States

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Oak Ridge, Tennessee, United States

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Amarillo, Texas, United States

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Fort Sam Houston, Texas, United States

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Houston, Texas, United States

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Odessa, Texas, United States

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San Antonio, Texas, United States

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Danville, Virginia, United States

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Puyallup, Washington, United States

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Buenos Aires, Argentina

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Caba, Argentina

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Ciudad de Buenos Aires, Argentina

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Cordooba, Argentina

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Corrientes, Argentina

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Córdoba, Argentina

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La Plata, Argentina

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Mar del Plata, Argentina

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Resistencia, Argentina

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Rosario, Argentina

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Salta, Argentina

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San Martín, Argentina

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Santa Fe, Argentina

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Brisbane, Australia

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Cairns, Australia

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Chermside, Australia

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Elizabeth Vale, Australia

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Herston, Australia

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Hobart, Australia

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Launceston, Australia

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Liverpool, Australia

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Murdoch, Australia

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Nambour, Australia

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New Lambton Heights, Australia

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Antwerp, Belgium

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Bonheiden, Belgium

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Brasschaat, Belgium

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Bruges, Belgium

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Edegem, Belgium

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Genk, Belgium

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Ghent, Belgium

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Huy, Belgium

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Liège, Belgium

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Mol, Belgium

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Roeselare, Belgium

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Ronse, Belgium

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Turnhout, Belgium

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Belo Horizonte, Brazil

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Blumenau, Brazil

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Campina Grande do Sul, Brazil

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Campinas, Brazil

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Curitiba, Brazil

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Marília, Brazil

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Passo Fundo, Brazil

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Porto Alegre, Brazil

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Recife, Brazil

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Salvador, Brazil

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São José do Rio Preto, Brazil

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São Paulo, Brazil

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Tatuí, Brazil

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Uberlândia, Brazil

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Votuporanga, Brazil

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Blagoevgrad, Bulgaria

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Burgas, Bulgaria

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Haskovo, Bulgaria

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Lovech, Bulgaria

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Pazardzhik, Bulgaria

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Pleven, Bulgaria

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Rousse, Bulgaria

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Sandanski, Bulgaria

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Sofia, Bulgaria

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Varna, Bulgaria

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Edmonton, Alberta, Canada

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New West Minister, British Columbia, Canada

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Victoria, British Columbia, Canada

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Greater Sudbury, Ontario, Canada

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London, Ontario, Canada

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Newmarket, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Saint-Charles-Borromée, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Québec, Canada

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Brno, Czechia

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Kolin Iii., Czechia

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Ostrava, Czechia

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Plzen-Bory, Czechia

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Prague, Czechia

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Třebíč, Czechia

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Znojmo, Czechia

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Herlev, Denmark

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Køge, Denmark

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Silkeborg, Denmark

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Besançon, France

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Chambray-lès-Tours, France

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Jossigny, France

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Le Coudray, France

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Lyon, France

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Montauban, France

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Nantes, France

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Périgueux, France

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Balatonfüred, Hungary

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Budapest, Hungary

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Debrecen, Hungary

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Győr, Hungary

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Gyula, Hungary

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Kaposvár, Hungary

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Kecskemét, Hungary

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Nyíregyháza, Hungary

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Székesfehérvár, Hungary

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Szolnok, Hungary

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Gifu, Japan

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Kagawa, Japan

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Kitakyushu, Japan

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Kobe, Japan

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Kumamoto, Japan

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Matsue, Japan

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Nagano, Japan

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Osaka, Japan

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Sayama-Shi, Japan

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Tokyo, Japan

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Uwajima-Shi, Japan

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Yokohama, Japan

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Yonago, Japan

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Yotsui 2-8-1, Japan

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's-Hertogenbosch, Netherlands

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Amersfoort, Netherlands

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Amsterdam, Netherlands

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Blaricum, Netherlands

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Den Helder, Netherlands

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Gouda, Netherlands

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Groningen, Netherlands

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Hoofddorp, Netherlands

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Hoogeveen, Netherlands

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Nijmegen, Netherlands

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Rotterdam, Netherlands

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Schiedam, Netherlands

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The Hague, Netherlands

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Bielsko-Biala, Poland

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Bytom, Poland

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Chrzanów, Poland

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Dąbrowa Górnicza, Poland

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Gdynia, Poland

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Grodzisk Mazowiecki, Poland

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Inowrocław, Poland

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Kędzierzyn-Koźle, Poland

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Kielce, Poland

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Koszalin, Poland

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Krakow, Poland

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Lodz, Poland

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Nowy Targ, Poland

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Nysa, Poland

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Oświęcim, Poland

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Polanica-Zdrój, Poland

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Puławy, Poland

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Tychy, Poland

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Warsaw, Poland

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Włocławek, Poland

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Barnaul, Russia

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Chita, Russia

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Ivanovo, Russia

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Kaliningrad, Russia

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Kemerovo, Russia

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Krasnodar, Russia

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Krasnoyarsk, Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Orenburg, Russia

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Penza, Russia

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Perm, Russia

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Rostov-on-Don, Russia

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Saint Petersburg, Russia

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Samara, Russia

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Syktyvkar, Russia

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Tyumen, Russia

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Yekaterinburg, Russia

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Gwangju, South Korea

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Incheon, South Korea

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Seongnam, South Korea

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Seoul, South Korea

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Suwon, South Korea

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A Coruña, Spain

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Almería, Spain

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Ávila, Spain

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Barcelona, Spain

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Madrid, Spain

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Málaga, Spain

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Murcia, Spain

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Sant Boi de Llobregat, Spain

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Tarragona, Spain

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Falun, Sweden

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Jönköping, Sweden

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Linköping, Sweden

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Lund, Sweden

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Örebro, Sweden

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Östersund, Sweden

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Stockholm, Sweden

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Sundsvall, Sweden

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Uppsala, Sweden

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Adana, Turkey (Türkiye)

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Ankara, Turkey (Türkiye)

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Aydin, Turkey (Türkiye)

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Bursa, Turkey (Türkiye)

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Diyarbakır, Turkey (Türkiye)

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Eskişehir, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Kahramanmaraş, Turkey (Türkiye)

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Kocaeli, Turkey (Türkiye)

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Konya, Turkey (Türkiye)

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Sivas, Turkey (Türkiye)

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Cherkasy, Ukraine

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Dnipropetrovsk, Ukraine

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Kharkiv, Ukraine

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Kyiv, Ukraine

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Lutsk, Ukraine

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Lviv, Ukraine

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Odesa, Ukraine

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Ternopil, Ukraine

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Zaporizhzhia, Ukraine

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Zhytomyr, Ukraine

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Related Publications (4)

  • 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.

  • Povsic TJ, Ohman EM, Roe MT, White J, Rockhold FW, Montalescot G, Cornel JH, Nicolau JC, Steg PG, James S, Bode C, Welsh RC, Plotnikov AN, Mundl H, Gibson CM. P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes. JAMA Cardiol. 2019 Jul 1;4(7):680-684. doi: 10.1001/jamacardio.2019.1510.

  • Ohman EM, Roe MT, Steg PG, James SK, Povsic TJ, White J, Rockhold F, Plotnikov A, Mundl H, Strony J, Sun X, Husted S, Tendera M, Montalescot G, Bahit MC, Ardissino D, Bueno H, Claeys MJ, Nicolau JC, Cornel JH, Goto S, Kiss RG, Guray U, Park DW, Bode C, Welsh RC, Gibson CM. Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet. 2017 May 6;389(10081):1799-1808. doi: 10.1016/S0140-6736(17)30751-1. Epub 2017 Mar 18.

  • Povsic TJ, Roe MT, Ohman EM, Steg PG, James S, Plotnikov A, Mundl H, Welsh R, Bode C, Gibson CM. A randomized trial to compare the safety of rivaroxaban vs aspirin in addition to either clopidogrel or ticagrelor in acute coronary syndrome: The design of the GEMINI-ACS-1 phase II study. Am Heart J. 2016 Apr;174:120-8. doi: 10.1016/j.ahj.2016.01.004. Epub 2016 Jan 18.

MeSH Terms

Conditions

Acute Coronary SyndromeMyocardial InfarctionAngina, Unstable

Interventions

AspirinRivaroxabanClopidogrelTicagrelor

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisAngina PectorisChest PainPainNeurologic ManifestationsSigns and Symptoms

Intervention Hierarchy (Ancestors)

SalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsThiophenesSulfur CompoundsMorpholinesOxazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsTiclopidineThienopyridinesPyridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingAdenosinePurine NucleosidesPurinesNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Limitations and Caveats

Study population was homogenous with limited participation of non-Caucasian participants. Randomization was not performed for use of P2Y12 inhibitor; strata comparisons between bleeding and efficacy endpoints are confounded and were not planned.

Results Point of Contact

Title
Associate Director
Organization
Janssen Research & Development, LLC

Study Officials

  • Janssen Research & Development, LLC Clinical Trial

    Janssen Research & Development, LLC

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 13, 2014

First Posted

November 18, 2014

Study Start

April 20, 2015

Primary Completion

October 14, 2016

Study Completion

October 14, 2016

Last Updated

December 26, 2017

Results First Posted

November 13, 2017

Record last verified: 2017-11

Locations