E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
rivaroxaban
oral anticoagulant
nonvalvular atrial fibrillation
left atrial thrombus
transesopheageal echocardiography
thrombus resolution
stroke
thromboembolism
|
|
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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003662 |
E.1.2 | Term | Atrial flutter |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 |
The primary objective of the study is to explore the effect of rivaroxaban on the complete
resolution of LA/LAA thrombi at the end-of-treatment visit (after 6 weeks of treatment) in
subjects with nonvalvular AF or atrial flutter who have LA/LAA thrombus confirmed by TEE.
The term nonvalvular AF is used to imply that AF is not related to rheumatic valvular disease
(predominantly mitral stenosis) or prosthetic heart valves |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to describe the categories of thrombus outcome in subjects (based on whether resolved, reduced, unchanged, larger, or new) confirmed on TEE at the end-of-treatment visit (after 6 weeks of treatment); describe the incidence of the composite of stroke and non-CNS systemic embolism at the end-of-treatment visit (after 6 weeks of treatment) and during follow-up; describe the incidence of all bleeding (major and non-major) events at the end-of-treatment visit (after 6 weeks of treatment) and during follow-up. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men or women aged >/= 18 years
- Hemodynamically stable nonvalvular AF or atrial flutter
- LA/LAA thrombus documented at baseline by transesopheagel echocardiography (TEE) up to 72 hours prior to start of study medication
- vitamin K antagonist(s) (VKA)/ new oral anticoagulant(s) (NOAC)-naïve or untreated within 1 month prior to signing of the informed consent form or VKA pretreated but under ineffective INR levels (< 2.0, documented with at least 2
consecutive measurements that are at least 24 hours apart) within last 6 weeks
- Women of childbearing potential and men must agree to use adequate contraception when sexually active
|
|
E.4 | Principal exclusion criteria |
- Transient Ischemic Attack within 3 days prior to study inclusion
- Severe, disabling stroke (modified Rankin score of 4-5, inclusive) within 3 months or any stroke within 14 days before the start of study drug
- Acute thromboembolic events or thrombosis (venous/arterial) within the last 14 days prior to study inclusion
- Acute myocardial infarction within the last 14 days prior to study inclusion
- Cardiac-related criteria: Previous intracardiac thrombus, Free-floating ball thrombus, Intracardiac tumor, known left ventricular or aortic thrombus, active endocarditis
- Active bleeding or high risk for bleeding contraindicating anticoagulant therapy
- Concomitant drugs/therapies: Indication for anticoagulant therapy for a condition other than nonvalvular AF or atrial flutter (eg, VTE). Concomitant use of anticoagulant drugs, including VKA, or factor IIa or factor Xa inhibitors. Chronic aspirin therapy >100 mg or dual antiplatelet therapy. Concomitant use of strong inhibitors of both cytochrome P450 (CYP) 3A4 and P glycoprotein (P-gp), ie, all human immunodeficiency virus protease inhibitors and the following azole antimycotics agents—ketoconazole, itraconazole, voriconazole, and posaconazole—if used systemically
- Concomitant conditions: Childbearing potential without proper contraceptive measures, pregnancy, or breast feeding. Hypersensitivity to investigational treatment. Calculated creatinine clearance [CrCl] < 15 mL/minute at the screening visit. Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk. Any severe condition that would limit life expectancy to less than 3 months (eg, advanced malignancy, etc.). Planned invasive procedure with potential for uncontrolled bleeding or increased risk of stroke, including major surgery, cardiac catheterization, or cardioversion prior to the end-of-treatment TEE. Inability to take oral medication. Ongoing drug addiction or alcohol abuse
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point is the percentage of subjects with complete resolution of left atrial or left atrial appendage thrombus at the end of treatment.
Complete resolution is characterized as the subject is completely thrombus-free confirmed on transesopheagel echocardiography
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 6 weeks after the start of study drug |
|
E.5.2 | Secondary end point(s) |
1) Categories of thrombus outcome: resolved, reduced, unchanged, enlarged or new
2) The composite number of stroke and non-central nervous system systemic embolism events
3)The number of all bleeding events |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For categories of thrombus outcome, it is at 6 weeks after the start of study drug.
For composite number of stroke, non-central nervous system systemic events, it is upto 12 weeks after the start of study drug |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarkers (collected from VKA/NOAC naive/untreated subgroup )of prothrombotic status (plasma F 1+2 and TAT complex),biomarkers of inflammatory response (high-sensitivity interleukin-6 [hs-IL-6] and high-sensitivity C-reactive protein [hs-CRP]), biomarker of thrombogenesis (D-dimers), biomarker of fibrinolysis (PAI-1 antigen), biomarker of endothelial damage/dysfunction (vWF) |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
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 |
Bulgaria |
France |
Germany |
Poland |
Russian Federation |
Turkey |
Ukraine |
|
E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |