Clinical trial NCT02293395: 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
Official title: A Randomized, Double-Blind, Double-Dummy, Active-controlled, Parallel-group, Multicenter Study to Compare the Safety of Rivaroxaban Versus Acetylsalicylic Acid in Addition to Either Clopidogrel or Ticagrelor Therapy in Subjects With Acute Coronary Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
Collaborators: name: Bayer
name: Duke Clinical Research Institute
name: Harvard Medical School (HMS and HSDM)
First posted: 2014-11-18
Enrollment: 3037
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Non Coronary Artery Bypass Graft-Related (Non CABG-related) Thrombolysis in Myocardial Infarction (TIMI) Clinically Significant Bleeding Events
timeFrame: From start of study treatment until follow-up (up to 390 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Alexander City
country: United States
state: Alabama
city: Banning
country: United States
state: California
city: Sylmar
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Littleton
country: United States
state: Colorado
city: Jupiter
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Pensacola
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Athens
country: United States
state: Georgia
city: Cumming
country: United States
state: Georgia
city: Macon
country: United States
state: Georgia
city: Tucker
country: United States
state: Georgia
city: Boise
country: United States
state: Idaho
city: Coeur d'Alene
country: United States
state: Idaho
city: Jerseyville
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Munster
country: United States
state: Indiana
city: Bay City
country: United States
state: Michigan
city: Kalamazoo
country: United States
state: Michigan
city: Lansing
country: United States
state: Michigan
city: Mount Clemens
country: United States
state: Michigan
city: Ypsilanti
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Columbia
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Kalispell
country: United States
state: Montana
city: Stony Brook
country: United States
state: New York
city: Rocky Mount
country: United States
state: North Carolina
city: Sanford
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Zanesville
country: United States
state: Ohio
city: Bartlesville
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Abington
country: United States
state: Pennsylvania
city: Langhorne
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Sayre
country: United States
state: Pennsylvania
city: York
country: United States
state: Pennsylvania
city: Rapid City
country: United States
state: South Dakota
city: Oak Ridge
country: United States
state: Tennessee
city: Amarillo
country: United States
state: Texas
city: Fort Sam Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Odessa
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Danville
country: United States
state: Virginia
city: Puyallup
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Caba
country: Argentina
city: Ciudad De Buenos Aires
country: Argentina
city: Cordooba
country: Argentina
city: Corrientes
country: Argentina
city: Córdoba
country: Argentina
city: La Plata
country: Argentina
city: Mar Del Plata
country: Argentina
city: Resistencia
country: Argentina
city: Rosario
country: Argentina
city: Salta
country: Argentina
city: San Martín
country: Argentina
city: Santa Fe
country: Argentina
city: Brisbane
country: Australia
city: Cairns
country: Australia
city: Chermside
country: Australia
city: Elizabeth Vale
country: Australia
city: Herston
country: Australia
city: Hobart
country: Australia
city: Launceston
country: Australia
city: Liverpool
country: Australia
city: Murdoch
country: Australia
city: Nambour
country: Australia
city: New Lambton Heights
country: Australia
city: Antwerpen
country: Belgium
city: Bonheiden
country: Belgium
city: Brasschaat
country: Belgium
city: Brugge
country: Belgium
city: Edegem
country: Belgium
city: Genk
country: Belgium
city: Gent
country: Belgium
city: Huy
country: Belgium
city: Liège
country: Belgium
city: Mol
country: Belgium
city: Roeselare
country: Belgium
city: Ronse
country: Belgium
city: Turnhout
country: Belgium
city: Belo Horizonte
country: Brazil
city: Blumenau
country: Brazil
city: Campina Grande Do Sul
country: Brazil
city: Campinas
country: Brazil
city: Curitiba
country: Brazil
city: Marília
country: Brazil
city: Passo Fundo
country: Brazil
city: Porto Alegre
country: Brazil
city: Recife
country: Brazil
city: Salvador
country: Brazil
city: São José Do Rio Preto
country: Brazil
city: São Paulo
country: Brazil
city: Tatuí
country: Brazil
city: Uberlândia
country: Brazil
city: Votuporanga
country: Brazil
city: Blagoevgrad
country: Bulgaria
city: Burgas
country: Bulgaria
city: Haskovo
country: Bulgaria
city: Lovech
country: Bulgaria
city: Pazardzhik
country: Bulgaria
city: Pleven
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sandanski
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Edmonton
country: Canada
state: Alberta
city: New West Minister
country: Canada
state: British Columbia
city: Victoria
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Newmarket
country: Canada
state: Ontario
city: Sudbury
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Saint-Charles-Borromée
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Québec
country: Canada
city: Brno
country: Czechia
city: Kolin Iii.
country: Czechia
city: Ostrava
country: Czechia
city: Plzen-Bory
country: Czechia
city: Praha 1
country: Czechia
city: Praha 2
country: Czechia
city: Trebic
country: Czechia
city: Znojmo
country: Czechia
city: Herlev
country: Denmark
city: Koge
country: Denmark
city: Silkeborg
country: Denmark
city: Besançon
country: France
city: Chambray Les Tours
country: France
city: Jossigny
country: France
city: Le Coudray
country: France
city: Lyon
country: France
city: Montauban
country: France
city: Nantes Cedex 1
country: France
city: Nantes
country: France
city: Périgueux
country: France
city: Balatonfüred
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Gyula
country: Hungary
city: Győr
country: Hungary
city: Kaposvar
country: Hungary
city: Kecskemét
country: Hungary
city: Nyíregyháza
country: Hungary
city: Szolnok
country: Hungary
city: Székesfehérvár
country: Hungary
city: Gifu
country: Japan
city: Kagawa
country: Japan
city: Kitakyushu-City
country: Japan
city: Kobe-Shi
country: Japan
city: Kumamoto-Shi
country: Japan
city: Kumamoto
country: Japan
city: Matsue-Shi
country: Japan
city: Nagano-Shi
country: Japan
city: Osaka-Shi
country: Japan
city: Sayama-Shi
country: Japan
city: Tokyo
country: Japan
city: Uwajima-Shi
country: Japan
city: Yokohama
country: Japan
city: Yonago
country: Japan
city: Yotsui 2-8-1
country: Japan
city: Gwangju
country: Korea, Republic of
city: Incheon
country: Korea, Republic of
city: Seongnam
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Amersfoort
country: Netherlands
city: Amsterdam
country: Netherlands
city: Blaricum
country: Netherlands
city: Den Haag
country: Netherlands
city: Den Helder
country: Netherlands
city: Gouda
country: Netherlands
city: Groningen
country: Netherlands
city: Hoofddorp
country: Netherlands
city: Hoogeveen
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: S-Hertogenbosch
country: Netherlands
city: Schiedam
country: Netherlands
city: Bielsko-Biala
country: Poland
city: Bytom
country: Poland
city: Chrzanow
country: Poland
city: Dabrowa Gornicza
country: Poland
city: Gdynia
country: Poland
city: Grodzisk Mazowiecki
country: Poland
city: Inowrocław
country: Poland
city: Kedzierzyn-Kozle
country: Poland
city: Kielce
country: Poland
city: Koszalin
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Nowy Targ
country: Poland
city: Nysa
country: Poland
city: Oswiecim
country: Poland
city: Polanica Zdroj
country: Poland
city: Pulawy
country: Poland
city: Tychy
country: Poland
city: Warszawa
country: Poland
city: Wloclawek
country: Poland
city: Barnaul
country: Russian Federation
city: Chita
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Kaliningrad
country: Russian Federation
city: Kemerovo
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Krasnoyarsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhniy Novgorod
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Penza
country: Russian Federation
city: Perm
country: Russian Federation
city: Rostov On Don
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Samara
country: Russian Federation
city: Syktyvkar
country: Russian Federation
city: Tyumen
country: Russian Federation
city: A Coruña
country: Spain
city: Almería
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Murcia
country: Spain
city: Málaga
country: Spain
city: Sant Boi De Llobregat
country: Spain
city: Tarragona
country: Spain
city: Ávila
country: Spain
city: Falun
country: Sweden
city: Jönköping
country: Sweden
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Stockholm
country: Sweden
city: Sundsvall
country: Sweden
city: Uppsala
country: Sweden
city: Örebro
country: Sweden
city: Östersund
country: Sweden
city: Adana
country: Turkey
city: Ankara
country: Turkey
city: Aydin
country: Turkey
city: Bursa
country: Turkey
city: Diyarbakir
country: Turkey
city: Eskisehir
country: Turkey
city: Istanbul
country: Turkey
city: Kahramanmaras
country: Turkey
city: Kocaeli
country: Turkey
city: Konya
country: Turkey
city: Sivas
country: Turkey
city: Cherkasy
country: Ukraine
city: Dnipropetrovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lutsk
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Ternopil
country: Ukraine
city: Zaporizhzhia
country: Ukraine
city: Zhytomyr
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.