A Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Participants With Acute Coronary Syndrome

NCT ID: NCT02293395

Last Updated: 2017-12-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 3037 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-20
• Study Completion Date: 2016-10-14

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]).

Detailed Description

This is a prospective, randomized (the study drug is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives), active-controlled (study in which the experimental treatment or procedure is compared to a standard treatment or procedure), parallel group (each group of participants will be treated at the same time), multicenter (when more than one hospital or medical school team work on a medical research study) study in participants with a recent ACS (STEMI or NSTE-ACS). All the eligible participants receiving background treatment of ASA plus clopidogrel (Stratum 1) or ASA plus ticagrelor (Stratum 2) will be randomly assigned to either receive ASA or rivaroxaban on background of P2Y12 receptor antagonists treatment. This study will include 3 phases: Screening Phase (up to 10 days, before study start on Day 1), Double-blind Treatment Phase (up to either 180 days after randomization of the last enrolled participant in the study or Day 360, whichever occurs earlier), and Follow-up Phase (up to 30 days). Participants' safety will be monitored throughout the study.

Conditions

Acute Coronary Syndrome

Keywords

Acute Coronary Syndrome; Myocardial infarction; Unstable angina; Acetylsalicylic acid; Rivaroxaban; JNJ-39039039; Bay 59-7939; Xarelto; Clopidogrel; Ticagrelor; Plavix; Brilinta; Effient

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Stratum 1/ASA

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.

Group Type: ACTIVE_COMPARATOR

Acetylsalicylic acid

Intervention Type: DRUG

ASA 100 mg enteric-coated tablet once daily orally.

Clopidogrel

Intervention Type: DRUG

Clopidogrel 75 mg once daily orally.

Stratum 1/Rivaroxaban

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.

Group Type: EXPERIMENTAL

Rivaroxaban

Intervention Type: DRUG

Rivaroxaban 2.5 mg tablet twice daily orally.

Clopidogrel

Intervention Type: DRUG

Clopidogrel 75 mg once daily orally.

Stratum 2/ASA

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.

Group Type: ACTIVE_COMPARATOR

Acetylsalicylic acid

Intervention Type: DRUG

ASA 100 mg enteric-coated tablet once daily orally.

Ticagrelor

Intervention Type: DRUG

Ticagrelor 90 mg twice daily orally.

Stratum 2/Rivaroxaban

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.

Group Type: EXPERIMENTAL

Rivaroxaban

Intervention Type: DRUG

Rivaroxaban 2.5 mg tablet twice daily orally.

Ticagrelor

Intervention Type: DRUG

Ticagrelor 90 mg twice daily orally.

Interventions

Acetylsalicylic acid

ASA 100 mg enteric-coated tablet once daily orally.

Intervention Type: DRUG

Rivaroxaban

Rivaroxaban 2.5 mg tablet twice daily orally.

Intervention Type: DRUG

Clopidogrel

Clopidogrel 75 mg once daily orally.

Intervention Type: DRUG

Ticagrelor

Ticagrelor 90 mg twice daily orally.

Intervention Type: DRUG

Other Intervention Names

Aspirin; JNJ-39039039; Bay 59-7939; Xarelto; Plavix; Brilinta

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Duke Clinical Research Institute

OTHER

Sponsor Role: collaborator

Harvard Medical School (HMS and HSDM)

OTHER

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Alexander City, Alabama, United States

Banning, California, United States

Sylmar, California, United States

Aurora, Colorado, United States

Littleton, Colorado, United States

Jupiter, Florida, United States

Miami, Florida, United States

Orlando, Florida, United States

Pensacola, Florida, United States

Tampa, Florida, United States

Athens, Georgia, United States

Cumming, Georgia, United States

Macon, Georgia, United States

Tucker, Georgia, United States

Boise, Idaho, United States

Coeur d'Alene, Idaho, United States

Jerseyville, Illinois, United States

Indianapolis, Indiana, United States

Munster, Indiana, United States

Bay City, Michigan, United States

Kalamazoo, Michigan, United States

Lansing, Michigan, United States

Mount Clemens, Michigan, United States

Ypsilanti, Michigan, United States

Minneapolis, Minnesota, United States

Columbia, Missouri, United States

St Louis, Missouri, United States

Kalispell, Montana, United States

Stony Brook, New York, United States

Rocky Mount, North Carolina, United States

Sanford, North Carolina, United States

Cincinnati, Ohio, United States

Zanesville, Ohio, United States

Bartlesville, Oklahoma, United States

Tulsa, Oklahoma, United States

Abington, Pennsylvania, United States

Langhorne, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Sayre, Pennsylvania, United States

York, Pennsylvania, United States

Rapid City, South Dakota, United States

Oak Ridge, Tennessee, United States

Amarillo, Texas, United States

Fort Sam Houston, Texas, United States

Houston, Texas, United States

Odessa, Texas, United States

San Antonio, Texas, United States

Danville, Virginia, United States

Puyallup, Washington, United States

Buenos Aires, , Argentina

Caba, , Argentina

Ciudad de Buenos Aires, , Argentina

Cordooba, , Argentina

Corrientes, , Argentina

Córdoba, , Argentina

La Plata, , Argentina

Mar del Plata, , Argentina

Resistencia, , Argentina

Rosario, , Argentina

Salta, , Argentina

San Martín, , Argentina

Santa Fe, , Argentina

Brisbane, , Australia

Cairns, , Australia

Chermside, , Australia

Elizabeth Vale, , Australia

Herston, , Australia

Hobart, , Australia

Launceston, , Australia

Liverpool, , Australia

Murdoch, , Australia

Nambour, , Australia

New Lambton Heights, , Australia

Antwerp, , Belgium

Bonheiden, , Belgium

Brasschaat, , Belgium

Bruges, , Belgium

Edegem, , Belgium

Genk, , Belgium

Ghent, , Belgium

Huy, , Belgium

Liège, , Belgium

Mol, , Belgium

Roeselare, , Belgium

Ronse, , Belgium

Turnhout, , Belgium

Belo Horizonte, , Brazil

Blumenau, , Brazil

Campina Grande do Sul, , Brazil

Campinas, , Brazil

Curitiba, , Brazil

Marília, , Brazil

Passo Fundo, , Brazil

Porto Alegre, , Brazil

Recife, , Brazil

Salvador, , Brazil

São José do Rio Preto, , Brazil

São Paulo, , Brazil

Tatuí, , Brazil

Uberlândia, , Brazil

Votuporanga, , Brazil

Blagoevgrad, , Bulgaria

Burgas, , Bulgaria

Haskovo, , Bulgaria

Lovech, , Bulgaria

Pazardzhik, , Bulgaria

Pleven, , Bulgaria

Rousse, , Bulgaria

Sandanski, , Bulgaria

Sofia, , Bulgaria

Varna, , Bulgaria

Edmonton, Alberta, Canada

New West Minister, British Columbia, Canada

Victoria, British Columbia, Canada

Greater Sudbury, Ontario, Canada

London, Ontario, Canada

Newmarket, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Saint-Charles-Borromée, Quebec, Canada

Sherbrooke, Quebec, Canada

Québec, , Canada

Brno, , Czechia

Kolin Iii., , Czechia

Ostrava, , Czechia

Plzen-Bory, , Czechia

Prague, , Czechia

Třebíč, , Czechia

Znojmo, , Czechia

Herlev, , Denmark

Køge, , Denmark

Silkeborg, , Denmark

Besançon, , France

Chambray-lès-Tours, , France

Jossigny, , France

Le Coudray, , France

Lyon, , France

Montauban, , France

Nantes, , France

Périgueux, , France

Balatonfüred, , Hungary

Budapest, , Hungary

Debrecen, , Hungary

Győr, , Hungary

Gyula, , Hungary

Kaposvár, , Hungary

Kecskemét, , Hungary

Nyíregyháza, , Hungary

Székesfehérvár, , Hungary

Szolnok, , Hungary

Gifu, , Japan

Kagawa, , Japan

Kitakyushu, , Japan

Kobe, , Japan

Kumamoto, , Japan

Matsue, , Japan

Nagano, , Japan

Osaka, , Japan

Sayama-Shi, , Japan

Tokyo, , Japan

Uwajima-Shi, , Japan

Yokohama, , Japan

Yonago, , Japan

Yotsui 2-8-1, , Japan

's-Hertogenbosch, , Netherlands

Amersfoort, , Netherlands

Amsterdam, , Netherlands

Blaricum, , Netherlands

Den Helder, , Netherlands

Gouda, , Netherlands

Groningen, , Netherlands

Hoofddorp, , Netherlands

Hoogeveen, , Netherlands

Nijmegen, , Netherlands

Rotterdam, , Netherlands

Schiedam, , Netherlands

The Hague, , Netherlands

Bielsko-Biala, , Poland

Bytom, , Poland

Chrzanów, , Poland

Dąbrowa Górnicza, , Poland

Gdynia, , Poland

Grodzisk Mazowiecki, , Poland

Inowrocław, , Poland

Kędzierzyn-Koźle, , Poland

Kielce, , Poland

Koszalin, , Poland

Krakow, , Poland

Lodz, , Poland

Nowy Targ, , Poland

Nysa, , Poland

Oświęcim, , Poland

Polanica-Zdrój, , Poland

Puławy, , Poland

Tychy, , Poland

Warsaw, , Poland

Włocławek, , Poland

Barnaul, , Russia

Chita, , Russia

Ivanovo, , Russia

Kaliningrad, , Russia

Kemerovo, , Russia

Krasnodar, , Russia

Krasnoyarsk, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Orenburg, , Russia

Penza, , Russia

Perm, , Russia

Rostov-on-Don, , Russia

Saint Petersburg, , Russia

Samara, , Russia

Syktyvkar, , Russia

Tyumen, , Russia

Yekaterinburg, , Russia

Gwangju, , South Korea

Incheon, , South Korea

Seongnam, , South Korea

Seoul, , South Korea

Suwon, , South Korea

A Coruña, , Spain

Almería, , Spain

Ávila, , Spain

Barcelona, , Spain

Madrid, , Spain

Málaga, , Spain

Murcia, , Spain

Sant Boi de Llobregat, , Spain

Tarragona, , Spain

Falun, , Sweden

Jönköping, , Sweden

Linköping, , Sweden

Lund, , Sweden

Örebro, , Sweden

Östersund, , Sweden

Stockholm, , Sweden

Sundsvall, , Sweden

Uppsala, , Sweden

Adana, , Turkey (Türkiye)

Ankara, , Turkey (Türkiye)

Aydin, , Turkey (Türkiye)

Bursa, , Turkey (Türkiye)

Diyarbakır, , Turkey (Türkiye)

Eskişehir, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Kahramanmaraş, , Turkey (Türkiye)

Kocaeli, , Turkey (Türkiye)

Konya, , Turkey (Türkiye)

Sivas, , Turkey (Türkiye)

Cherkasy, , Ukraine

Dnipropetrovsk, , Ukraine

Kharkiv, , Ukraine

Kyiv, , Ukraine

Lutsk, , Ukraine

Lviv, , Ukraine

Odesa, , Ukraine

Ternopil, , Ukraine

Zaporizhzhia, , Ukraine

Zhytomyr, , Ukraine

Countries

United States; Argentina; Australia; Belgium; Brazil; Bulgaria; Canada; Czechia; Denmark; France; Hungary; Japan; Netherlands; Poland; Russia; South Korea; Spain; Sweden; Turkey (Türkiye); Ukraine

References

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.

Reference Type: DERIVED

PMID: 31535314 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31141104 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28325638 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26995378 (View on PubMed)

Other Identifiers

RIVAROXACS2002

Identifier Type: OTHER

Identifier Source: secondary_id

2014-004266-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR106261

Identifier Type: -

Identifier Source: org_study_id