Primary objectives:*To determine whether rivaroxaban 2.5 mg twice daily (bid) + aspirin 100 mg once daily (od) compared with aspirin 100 mg od reduces therisk of a composite of myocardial infarction, stroke, or cardiovascular death in subjects with…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy: Composite of myocardial infarction, stroke, or cardiovascular death.
Safety: modified International Society on Thrombosis and Haemostasis major
bleeding.
LTOLE: the same primary safety and efficacy variables will be collected.
Secondary outcome
Composite of myocardial infarction, stroke, cardiovascular death,
revasculatization and venous thromboembolism and cardiovascular hospitalization.
Mortality.
Upper gastrointestinal bleeding, ulceration, and gastrointestinal obstruction
or perforation.
Background summary
COMPASS is a Phase III trial that will investigate the prevention of major
adverse cardiac events (MACE) including cardiovascular death, myocardial
infarction and stroke in patients with coronary artery disease (CAD) or
peripheral artery disease (PAD).
The COMPASS study will assess the potential of rivaroxaban to provide
additional prevention of cardiovascular events to patients when added to
aspirin, as well as investigating rivaroxaban and aspirin as single treatments.
Patients will also be randomized to receive a proton pump inhibitor.
Study objective
Primary objectives:
*To determine whether rivaroxaban 2.5 mg twice daily (bid) + aspirin 100 mg
once daily (od) compared with aspirin 100 mg od reduces the
risk of a composite of myocardial infarction, stroke, or cardiovascular death
in subjects with CAD or PAD
*To determine whether rivaroxaban 5 mg bid compared with aspirin 100 mg od
reduces the risk of a composite of myocardial infarction, stroke or
cardiovascular death in subjects with CAD or PAD
Secondary objectives:
*To determine whether each of rivaroxaban 2.5 mg bid + aspirin 100 mg od and
rivaroxaban 5 mg bid alone reduces the risk of the composite of
major thrombotic events (coronary heart disease, myocardial infarction,
ischemic stroke, acute limb ischemia; cardiovascular death) compared with
aspirin 100 mg od in subjects with CAD or PAD
*To determine whether each of rivaroxaban 2.5 mg bid + aspirin 100 mg od and
rivaroxaban 5 mg bid alone reduces the risk of mortality in
subjects with CAD or PAD
Objective for Long-Term Open-Label Extension (LTOLE)
To make rivaroxaban 2.5 mg twice daily (bid) + aspirin 100 mg once daily (od)
available to COMPASS trial subjects until the rivaroxaban treatment is
commercially available for this indication or for approximately 3 years from
regulatory approval of LTOLE in a country, whichever comes first.
Study design
Randomized, double-blind, controlled phase III trial with a 3 x 2 partial
factorial design.
Screening, run-in, follow-up and washout periods.
The run-in period will occur during the 30 days prior to initiation of study
treatment, with the exception of subjects randomized after CABG who will not
require a run-in. These patients will not be enrolled in NL. During run-in,
subjects will discontinue any current anticoagulant therapy and will begin
rivaroxaban placebo and 100 mg aspirin.
Treatment will begin on Day 0, which will also signal the initiation of the
follow-up period. Subjects will be randomized 1:1 to pantoprazole or
pantoprazole placebo and then will be randomized 1:1:1 to rivaroxaban and
aspirin or their matching placebos:
- Rivaroxaban 2.5 mg bid + Aspirin 100 mg od + Pantoprazole 40 mg od
- Rivaroxaban 2.5 mg bid + Aspirin 100 mg od + Pantoprazole placebo
- Rivaroxaban 5 mg bid + Aspirin placebo + Pantoprazole 40 mg od
- Rivaroxaban 5 mg bid + Aspirin placebo + Pantoprazole placebo
- Rivaroxaban placebo + Aspirin 100 mg od + Pantoprazole 40 mg od
- Rivaroxaban placebo + Aspirin 100 mg od + Pantoprazole placebo
NB: Subjects already taking a proton pump inhibitor at baseline will undergo
only a single randomization (to rivaroxaban 2.5 mg bid + aspirin 100 mg od,
rivaroxaban 5 mg bid + aspirin placebo or rivaroxaban placebo + aspirin 100 mg
od).
NL will not participate in both substudies (proteomics and brain MRI).
A final follow-up visit will occur when a minimum of 2,200 subjects experience
an event for the primary efficacy outcome.
Patient numbers wordwide: enrolled = 29.940; randomized = 27.400.
Independent data safety monitoring board.
LTOLE: open label uncontrolled study
Intervention
Treatment with
rivaroxaban or placebo,
aspirine or placebo,
pantoprazole or placebo.
LTOLE: bi daily 2.5mg rivaroxaban and once daily 100mg aspirine
Study burden and risks
Risk: Adverse events of the study medication, in particular increased bleeding
(if any).
Burden: The study is designed to closely follow routine clinical practice,
therefore the burden to patients from the study related procedures including
the blood sampling and visits is expected to be minimal. Approx. 17 study
visits when study duration = 5 years.
LTOLE:
Risk: Adverse events of the study medication, in particular increased bleeding
(if any).
Burden: The study is designed to closely follow routine clinical practice,
therefore the burden to patients from the study related procedures including
the potential blood sampling and visits is expected to be minimal. Approx. 7
study visits when study duration = 3 years.
Energieweg 1
Mijdrecht 3641 RT
NL
Energieweg 1
Mijdrecht 3641 RT
NL
Listed location countries
Age
Inclusion criteria
CAD or PAD (see protocol for definitions) plus at least one of the following:
o Age *65
o Age <65 plus documented atherosclerosis in two vascular beds or at least 2
additional risk factors (see protocol for details) ;All subjects randomized to the COMPASS trial willing to consent to LTOLE are
eligible unless the subjects developed a condition considered by the investigator as
exclusionary.
* Subjects who have given their written informed consent to participate in the LTOLE
after having received adequate information prior to any LTOLE specific procedures.
Exclusion criteria
- High risk of bleeding
- Stroke within 1 month or any history of hemorrhagic or lacunar stroke
- Ejection fraction <30% or NYHA class III or IV symptoms
- eGFR<15 mL/min
- Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy or oral anticoagulant therapy
- Systemic treatment with strong CYP 3A4 and P-gp inhibitors
- Inadequate contraception for females of childbearing potential
- Pregnancy, breast feeding;Subjects should not be included in the LTOLE study if, in the judgement of the investigator, they have
developed a condition which should exclude them from receiving LTOLE study
medication. For example if the subject has developed atrial fibrillation or had a severe
allergic rash while in the study, which subsided when drug was stopped and returned
when drug was reinitiated.
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 |
|---|---|
| Other | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2012-004180-43-NL |
| CCMO | NL43921.060.13 |