To estimate the bleeding risk with rivaroxaban, compared with ASA, in addition to a singleantiplatelet agent (clopidogrel or ticagrelor), in subjects with a recent ACS .
ID
Source
Brief title
Condition
- Myocardial disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is the composite of TIMI clinically
significant bleeding events that
consists of non CABG-related TIMI major bleeding events, TIMI minor bleeding
events, and TIMI
bleeding events requiring medical attention.
Secondary outcome
The efficacy of Rivaroxaban compared with ASA, in addition to a single
antipletelet agent (clopidogrel or ticagrelor), will be explored, in reducing
the risk of the composite of CV death, MI, ischemic stroke and stent thrombosis
in subjects with a recent ACS.
Background summary
Rivaroxaban (JNJ-39039039; BAY 59-7939) is an oral anticoagulant. The mechanism
of action of
rivaroxaban is to selectively and directly inhibit Factor Xa (FXa), which plays
a central role in the
cascade of blood coagulation by mediating thrombin formation. Rivaroxaban does
not require metabolic
conversion or a cofactor to exert its activity.
Rivaroxaban is marketed under the trade name XARELTO® and has been approved
worldwide for the
treatment of multiple thrombosis-mediated conditions. XARELTO co-administered
with acetylsalicylic
acid (ASA) alone or with ASA plus clopidogrel or ticlopidine has been approved
in the European Union
(EU) for the prevention of atherothrombotic events in adult patients after an
acute coronary syndrome
(ACS) with elevated cardiac biomarkers.
Study objective
To estimate the bleeding risk with rivaroxaban, compared with ASA, in addition
to a single
antiplatelet agent (clopidogrel or ticagrelor), in subjects with a recent ACS .
Study design
This is a prospective, randomized, double-blind, double-dummy,
active-controlled, parallel-group,
multicenter study to evaluate the safety and efficacy of rivaroxaban 2.5 mg
twice daily compared with
ASA 100 mg once daily, in addition to a single antiplatelet agent (clopidogrel
75 mg once daily or
ticagrelor 90 mg twice daily), for a minimum of 180 days, and up to 360 days of
treatment, in subjects
with a recent ACS (STEMI or NSTE-ACS). The number of subjects with STEMI
enrolled in the study
will be limited to no more than 50% of all subjects.
Approximately 3,000 eligible subjects receiving maintenance treatment of ASA
plus clopidogrel or ASA
plus ticagrelor for ACS will be stratified by the background P2Y12 inhibitor
used. All subjects must
receive dual antiplatelet therapy (DAPT; ASA in combination with a P2Y12
inhibitor, clopidogrel or
ticagrelor) for treatment of the index event for a minimum of 48 hours prior to
randomization. When
treatment with P2Y12 inhibitor has changed during the screening period, the
stratification will be based on
the P2Y12 inhibitor used for the immediate 48 hours prior to randomization, and
with the intention to
continue after randomization. Approximately 1,500 subjects are planned for
enrollment in each stratum.
The selection of the P2Y12 inhibitor, clopidogrel or ticagrelor, will be made
at least 48 hours prior to
randomization by the managing physician, and maintained throughout the study,
except in cases where
discontinuation is medically indicated. It is strongly recommended that the
intended duration of P2Y12
treatment should be consistent with societal guidelines for patients with ACS
(eg, the American Heart
Association/American College of Cardiology Foundation guidelines, the European
Society of Cardiology
guidelines), which recommend that P2Y12 treatment be maintained up to or over
12 months.
Intervention
PAtient will be assigned rivaroxaban + placebo together with ticagrelor or
clopidogrel ór ASA + placebo togehter with ticagrelor or clopidogrel.
There are 2 treatment groups in this study:
• Rivaroxaban 2,5mg b.i.d.
• Aspirin 100mg
Study burden and risks
For side effects related to Rivaroxaban, ASA, Clopidogrel and Prasugrel I refer
to the Informed Consent Form (appendix C).
Side effects from tests:
• Blood draw: Taking blood may cause bruising at the place where the needle
goes into the skin. Fainting, and in rare cases infection, may occur.
Antwerpseweg 15-17
Beerse 2340
NL
Antwerpseweg 15-17
Beerse 2340
NL
Listed location countries
Age
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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-004266-26-NL |
| ClinicalTrials.gov | NCT02293395 |
| CCMO | NL52090.056.15 |