E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of major cardiovascular events in patients with coronary or peripheral artery disease |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of heart attacks, strokes and death in patients with (atherosclerotic) narrowing of the arteries of the heart or legs |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064939 |
E.1.2 | Term | Cardiovascular event prophylaxis |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objectives for rivaroxaban randomization:
•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
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E.2.2 | Secondary objectives of the trial |
Secondary objectives for rivaroxaban randomization:
•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 death, myocardial
infarction, ischemic stroke, acute limb ischemia; cardiovascular death,
myocardial infarction, ischemic stroke, acute limb ischemia) 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 |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: COMPASS MIND
Date/Version: The COMPASS MIND substudy is included in section 14 of the COMPASS protocol
Objective: Magnetic resonance imaging (MRI) substudy evaluating the incidence of clinically silent brain infarcts and subclinical brain ischemia |
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E.3 | Principal inclusion criteria |
- Willing and able to provide written informed consent
- Meet criteria for CAD* and/or PAD
*Subjects with CAD must also meet at least one of the following:
•Age ≥65, or
•Age <65 plus documented atherosclerosis or revascularisation involving at least two vascular beds or at least 2 additional cardiovascular risk factors :
1) Current smoker (within 1 year or fandomisation)
2) Diabetes mellitus
3) Renal dysfunction with estimated glomerular filtration rate <60 ml/min
4) Heart failure
5) Non-lacunar ischemic stroke ≥ 1 month ago
§Because CAD involves disease in the coronary vasculature, only one additional vascular bed is required:e.g. the aorta and arterial supply to the brain, gastro-intestinal tract, lower limbs, upper limbs, or kidneys.
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E.4 | Principal exclusion criteria |
- High risk of bleeding
- Stroke within 1 month or any history of hemorrhagic or lacunar stroke
- Severe heart failure with known ejection fraction <30% or New York Heart Association (NYHA) class III or IV symptoms
- Estimated glomerular filtration rate (eGFR)<15 mL/min
- Need for dual antiplatelet therapy, other non-aspirin antiplatelet therapy or oral anticoagulant therapy
- Known non-cardiovascular disease that is associated with poor prognosis (e.g., metastatic cancer) or that increases the risk of an adverse reaction to study interventions.
- History of hypersensitivity or known contraindication for rivaroxaban, aspirin, pantoprazole, or excipients, if applicable.
- Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein (P-gp) (e.g., systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine
- Any known hepatic disease associated with coagulopathy
- Subjects who are pregnant, breastfeeding or are of childbearing potential, and sexually active and not practicing an effective method of birth control (e.g. surgically sterile, prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization)
- Previous assignment to treatment during this study
- Concomitant participation in another study with investigational drug
- Known contraindication to any study related procedures
An additional exclusion for the pantoprazole randomization is:
- Need for continuous treatment with a proton pump inhibitor
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy end point: Time from randomization to the first occurrence of either myocardial infarction, stroke, or cardiovascular death
Safety end point: Time from randomization to the first occurrence of major bleeding (modified International Society on Thrombosis and Haemostasis) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Time from randomization to first occurrence of either Coronary heart
disease death, myocardial infarction, ischemic stroke, acute limb
ischemia
Time from randomization to first occurrence of either Cardiovascular
death, myocardial infarction, ischemic stroke, acute limb ischemia
Time from randomization to first occurrence of all cause mortality |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To make rivaroxaban 2.5 mg twice daily twice daily + aspirin 100 mg once daily available to COMPASS trial subjects until the rivaroxaban treatment is commercially available for this indication or for approximately 3 years from regulatory approval of the long term open label extension in a country, whichever comes first. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 215 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
Chile |
China |
Colombia |
Czech Republic |
Denmark |
Ecuador |
Finland |
France |
Germany |
Hungary |
India |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Netherlands |
Philippines |
Poland |
Russian Federation |
Slovakia |
South Africa |
Sweden |
Switzerland |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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For each participating European Union (EU) country, the end of the study according to the EU Clinical Trial Directive will be reached when the telephone call at the end of the 30 day washout period for the last subject for all centers in the respective country has occurred. The end of the study as a whole will be reached as soon as the end of the study according to the above definition has been reached in all participating countries (EU and non-EU). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |