The aim of this study is to assess whether rivaroxaban, as compared to UFH, on the background of standard dual antiplatelet therapy (DAPT), can effectively suppress thrombosis, and related adverse ischemic events, upon balloon inflation and stent…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The anticoagulant effect will be determined during the index PCI procedure
based on the number of subjects who:
-Require bail-out anticoagulant therapy in the context of an ischemic coronary
event, and/or
-Experience an angiographic flow limiting thrombotic event (i.e. abrupt vessel
closure, visible thrombus, no-reflow) and/or
-Experience thrombus formation on the PCI equipment (i.e. guiding catheter and
guidewire thrombus) and/or
-Experience an MI due to the PCI procedure (i.e. procedural MI).
Note: The PCI procedure starts when the target lesion is crossed with the
guidewire and ends when the guiding catheter is removed and the subject has
left the catheterization laboratory.
Secondary outcome
Efficacy variables
- Separate components of the primary endpoint
- Clinical ischemic events up to 30 days after index PCI assessed by the
composite endpoint of:
- All death
- Non-fatal myocardial infarction (excluding those events due to the
procedure alone and reported as primary endpoint)
- Stroke
- Clinically indicated target lesion revascularization (TLR)
- The incidence of clinically indicated TLR up to 30 days after index PCI
- Definite and probable stent thrombosis up to 30 days after index PCI
according to the Academic Research Consortium (ARC) definition11
Safety variables
- Bleeding events up to 30 days after index PCI:
- Incidence of clinically significant bleeding according to:
- TIMI major
- TIMI minor
- Requiring medical attention
- Incidence of bleeding according to BARC type 2, 3 and 5
- Any other SAEs up to 30 days after index PCI
Background summary
During the percutaneous angioplasty procedure, the blood vessel wall can be
damaged. This damage can lead to an increase formation of a blood plug or clot.
A blood plug or clot is caused by blood components such as thrombin and blood
platelets. This blood clot can disrupt the flow of blood in the coronary artery
and can even rise the risk to block the blood vessel completely, which could
result in a heart attack. In order to prevent this it is generally recommended
to be on oral treatment with so called antiplatelet inhibitors as aspirin and
clopidogrel which decrease the effect of thrombin and blood platelets. In
addition to this an anticoagulant such as heparin will be given intravenously
during the procedure.
For more than 50 years heparin has been the most important drug for indirectly
inhibiting thrombin and therefore preventing clot formation. Despite its
unmistakable advantages, this drug also has some disadvantages such as:
- finding the correct individual dose (which is often difficult),
- risk of antibody production and
- route of administration as heparin needs to be administered via a vein
(intravenously).
Other new drugs with a similar effect as heparin are now being developed. The
study drug, Rivaroxaban (Xarelto®), which in contrast to heparin is a tablet
and will be taken orally, is a new anticoagulant that is being developed by
Bayer HealthCare AG in Germany.
Rivaroxaban is an oral active direct factor Xa inhibitor approved in September
2008 by the European Commission for the prevention of venous thromboembolism
(VTE) in adult patients undergoing elective hip or knee replacement surgery.
Rivaroxaban (Xarelto®) inhibits factor Xa which plays a central role in the
formation of a clot. Inhibiting factor Xa ensures that the effect of thrombin
is inhibited and thus prevents from clot formation.
Study objective
The aim of this study is to assess whether rivaroxaban, as compared to UFH, on
the background of standard dual antiplatelet therapy (DAPT), can effectively
suppress thrombosis, and related adverse ischemic events, upon balloon
inflation and stent expansion, during elective PCI, without increasing
bleeding.
The secondary objective is to investigate the safety of rivaroxaban plus DAPT
in the setting of elective PCI. Secondary objectives are safety criteria with
respect to bleeding Safety criteria with respect to bleeding (TIMI major, TIMI
minor and BARC type 2, 3 and 5) and the composite of clinical ischemic events
(all death, non-fatal MI, non-fatal stroke and target Lesion Revascularization)
be determined up to 30 days.
The coagulation profile and the plasma concentration of rivaroxaban will be
captured at various time points.
Study design
This is a prospective, randomized, heparin-controlled, multi-dose, semi-blind
study, conducted in Europe (Netherlands and Belgium). Prior to the elective PCI
a screening visit will be performed. The duration of the study will be 30 ± 7
days and ends with a follow-up telephone call at that time point.
Intervention
Study-specific intervention/therapy (e.g. apart from standardly performed PCI):
Patients participating in the study will receive 1 of the 2 doses rivaroxaban
(10 or 20 mg), or 10 mg rivaroxaban followed by 50 IU/kg unfractionated heparin
pre procedure (NB: the fourth group of patients will receive standard therapy
with heparin).
Study burden and risks
- Physical examination is done once
- Blood will be drawn 6-9 times (max 40 ml each time), depending on the
duration of the PCI. Every half hour a sample will be taken.
- 4 ECGs will be recorded
- A pregnancy test will be done for women.
.
Kaiser-Wilhelm-Allee
51368 Leverkusen
DE
Kaiser-Wilhelm-Allee
51368 Leverkusen
DE
Listed location countries
Age
Inclusion criteria
1) Male or female subject aged 18 years or more with no upper age limit and willing to comply with the protocol.;2) Symptomatic coronary artery disease due to undergo an elective (non- emergent) PCI on one or two lesions in the native coronary vessel(s). Cardiac standard troponin at baseline is within the normal limits.;3) Subject is able to read and give written informed consent and has signed an informed consent form approved by the Investigator's IRB/IEC after receiving detailed written and oral information prior to any study specific procedures.;4) Ability to understand and follow study-related instructions.
Exclusion criteria
1) Conditions that may increase the risk of the PCI procedure
• Lesion-specific conditions
• Clinical condition at screening visit:
2) Conditions that may increase the risk of bleeding (e.g. a clinically significant gastrointestinal bleeding within 12 months before randomization; history of hemorrhagic stroke; active internal bleeding etc.)
3) Concomitant conditions or diseases (e.g. known HIV infection at time of screening; significant valvular heart disease etc.)
40 Concomitant medication (e.g. current use of anticoagulant drugs; Chronic treatment with non-steroidal anti-inflammatory drugs, NSAIDs)
The complete list can be found in the protocol chapter 5.1.2 on page 33 till 35.
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 | EUCTR2011-001094-58-NL |
| CCMO | NL36665.060.11 |