Clinical trial NCT01839357: Exploring the Efficacy of Once Daily Oral Rivaroxaban for Treatment of Thrombus in Left Atrial/Left Atrial Appendage in Subjects With Nonvalvular Atrial Fibrillation or Atrial Flutter
Official title: An Open-label, International, Multicenter, Interventional Study Exploring the Efficacy of Once-daily Oral Rivaroxaban (BAY 59-7939) for the Treatment of Left Atrial/Left Atrial Appendage Thrombus in Subjects With Nonvalvular Atrial Fibrillation or Atrial Flutter
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Keywords: Rivaroxaban
Oral anticoagulant
Nonvalvular atrial fibrillation
Left atrial thrombus
Transesophageal echocardiography
Thrombus resolution
Stroke
Thromboembolism
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2013-04-24
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A study for subjects with atrial fibrillation (AF) or atrial flutter who are diagnosed with left atrial (LA) or left atrial appendage (LAA) thrombus. The study will assign subjects to rivaroxaban for treatment of thrombi. The study will measure thrombus outcomes based on echo image and common clinical outcomes such as bleeding and stroke or thromboembolism.


Eligibility criteria: Inclusion Criteria:

* Men or women aged \>/= 18 years
* Hemodynamically stable nonvalvular AF or atrial flutter
* LA/LAA thrombus documented at baseline by transesophageal 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
* 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

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 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, venous thromboembolism). 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

Primary outcomes:
measure: The percentage of subjects with complete resolution of left atrial or left atrial appendage thrombus at the end of treatment
timeFrame: After 6 weeks
Secondary outcomes:
measure: Categories of thrombus outcome in subjects: resolved, reduced, unchanged, enlarged or new
timeFrame: After 6 weeks
measure: The composite number of stroke and non-central nervous system systemic embolism events
timeFrame: Up to 12 weeks
measure: The number of all bleeding events
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Creteil
country: France
city: Marseille
country: France
city: Paris
country: France
city: TOULOUSE cedex
country: France
city: Bonn
country: Germany
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Warszawa
country: Poland
city: Wroclaw
country: Poland
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Saratov
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Istanbul
country: Turkey
city: Istanbul
country: Turkey
city: Istanbul
country: Turkey
city: Samsun
country: Turkey
city: Donetsk
country: Ukraine
city: Kiev
country: Ukraine
city: Odesa
country: Ukraine
city: Uzhhorod
country: Ukraine
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Lip GY, Hammerstingl C, Marin F, Cappato R, Meng IL, Kirsch B, Morandi E, van Eickels M, Cohen A. Rationale and design of a study exploring the efficacy of once-daily oral rivaroxaban (X-TRA) on the outcome of left atrial/left atrial appendage thrombus in nonvalvular atrial fibrillation or atrial flutter and a retrospective observational registry providing baseline data (CLOT-AF). Am Heart J. 2015 Apr;169(4):464-71.e2. doi: 10.1016/j.ahj.2014.12.020. Epub 2015 Jan 6.