excessive atrial ectopy or short atrial runs and high embolism risk MedDRA version: 20.0 Level: LLT Classification code 10042601 Term: Supraventricular ectopics System Organ Class: 100000004849
Conditions
Interventions
Trade Name: Xarelto 10 mg comprimé pelliculé
Product Name: XARELTO 10 mg
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Rivaroxaban
CAS Number: 366789-02-8
Concentration unit: mg milligram(s)
Sponsors
Assistance Publique - Hôpitaux de Paris
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: o Patients = 65 years old o Diagnosis of excessive supraventricular ectopy activity defined as = 1% PAC / 24 h or any atrial runs = 20 PACs on a 24-hour Holter ECG monitoring (the indication for the Holter will be let at the discretion of the doctor according to international guidelines indication) o High risk embolism defined by a CHA2DS2VASC score = 3 o Written consent from patient o Patients able to attend consultations and Cerebral MRI at baseline and 24 months at the participating centre. o Ability to understand and comply with the study protocol o Affiliation of social security regime Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 550
Exclusion criteria
Exclusion criteria: o According to the SmPC, any contraindication to Rivaroxaban (particularly patients with ongoing major bleeding, vascular complication, prior haemorrhagic stroke or over recent stroke) or one of its excipients. o Inability to perform cerebral MRI o Life expectancy <24 months o History of major hemorrhage after taking rivaroxaban o Documented atrial fibrillation or any other indication for oral anticoagulation o Patients with previous documented AF o Valvular congenital heart disease o Anticoagulant agents in the month prior to the inclusion visit o Acute coronary syndrome, coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery) or in the past 30 days o Requires long-term antiplatelet therapy other than aspirin (i.e., patient requires any platelet aggregation inhibitor in addition to study treatment, in particular, the combination of two platelet aggregation inhibitors) o Ongoing need for strong inhibitors of both CYP3A4 and P-glycoprotein (e.g., ketoconazole, itraconazole, ritonavir or clarithromycin) o Ongoing need for strong inducers of both CYP3A4 and P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin) o Participants considered by the investigator to be unsuitable for the study for any of the following reasons: ? Patient refuse the treatment with rivaroxaban or anticipated to have poor compliance on study drug treatment ? Unwilling to attend study follow-up visits o cancer or other life threatening conditions o Severe, disabling stroke within the previous 6 months, or any stroke within the previous 14 days o Conditions associated with an increased risk of bleeding: a. Major surgery within the previous month b. Planned surgery or intervention within the next 3 months c. History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding d. Gastrointestinal hemorrhage within the past year e. Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days f. Hemorrhagic disorder or bleeding diathesis g. Need for anticoagulant treatment of disorders other than atrial fibrillation h. Fibrinolytic agents within 48 hours of study entry i. Uncontrolled hypertension (systolic blood pressure greater than 180 mm Hg and/or diastolic blood pressure greater than 100 mm Hg) j. Recent malignancy or radiation therapy (within 6 months) and not expected to survive 3 years o Severe renal impairment (estimated creatinine clearance <30 mL/min or less) o Active infective endocarditis o Active liver disease, including but not limited to, associated or not with coagulopathy and a clinically significant risk of bleeding, including cirrhotic patients with a Child Pugh class B or C score. o Persistent ALT, AST, Alk Phos greater than twice the upper limit of the normal range o Known active hepatitis C (positive HCV RNA) o Known active hepatitis B (HBs antigen +, anti HBc IgM +) o Known active hepatitis A o Anemia (hemoglobin level less than 110 g/L) or thrombocytopenia (platelet count less than 150 X 109/L) o Patients who have received an investigational drug in the past 30 days o Patients considered unreliable by the investigator, or having any condition which, in the opinion of the investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse) o Patient with cardiac prosthetic devices : Reveal, pace-maker, automatic implantable defibrillator o Participation in another interventional clinical trial o Patient on
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the Short Run AF study is to evaluate the efficacy and safety of long term anticoagulation with rivaroxaban against standard of care (SOC) in patients with ESVEA and CHA2DS2VASC score =3 on the incidence of ischemic stroke and peripheral embolism after 2 years follow-up and the occurrence of major bleeding events. ;Secondary Objective: Secondary objectives will include: -Efficacy-related objectives: oTo compare randomized groups on net clinical benefit, major cardiovascular events, overall survival, cognitive decline. oTo compare randomized groups on individual components of composite primary and secondary efficacy endpoints -Exploratory objectives: oTo describe and compare between randomized groups the incidence of documented atrial fibrillation diagnosed from patient symptoms or systematic 24 hours ECG Holter performed at 1 year and 2-year follow-up. oTo evaluate through cerebral MRI the incidence of asymptomatic cerebral damage including silent cerebral ischemia and microbleeds at 2-year follow-up. -Safety-related objectives: oTo assess the occurrence of life-threatening or fatal bleeding, clinically relevant non-major bleeding intracranial hemorrhage and minor bleeding ;Primary end point(s): The primary efficacy endpoint is the first ischemic stroke or peripheral embolism detected clinically and on systematic cerebral MRIs in a time-to-event analysis. The primary safety outcome is major bleeding at any site in the body according to the criteria of the International Society of Thrombosis and Hemostasis (ISTH) ;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will include: - Efficacy-related endpoints: o A composite of ischemic stroke, peripheral embolism or major bleeding (net clinical benefit); a composite of death from cardiovascular causes, stroke, systemic embolism, myocardial infarction (major cardiovascular events); death from any cause; cognitive decline as assessed by the MMS (26). o Individual components of composite primary and secondary efficacy endpoints - Exploratory endpoints: o Incidence of documented atrial fibrillation diagnosed from patient symptoms or systematic 24 hours ECG Holter performed at 1- and 2-year follow-up. o Incidence of asymptomatic MRI-detected cerebral damage including silent cerebral ischemia and microbleeds at 2-year follow up. - Safety-related endpoints: o Life-threatening or fatal bleeding events, clinically relevant non-major bleeding intracranial hemorrhage and minor bleeding events. Bleeding severity will be assessed according to ISTH classification. ;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
France
Contacts
Public Contactproject Manager
Assistance Publique - Hôpitaux de Paris
Outcome results
None listed