Low-dose Versus Standard-dose Rivaroxaban in Elderly Patients With Atrial Fibrillation

The Efficacy and Safety of Low-dose Versus Standard-dose Rivaroxaban in Elderly Patients With Atrial Fibrillation

To evaluate the efficacy and safety of low-dose versus standard-dose rivaroxaban anticoagulation therapy in elderly patients with atrial fibrillation.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Atrial Fibrillation; Major Adverse Cardiac Events; Anticoagulant Adverse Reaction
• Intervention / Treatment: Drug: low-dose rivaroxaban; Drug: Standard-dose rivaroxaban

• Study Type: Interventional
• Enrollment (Estimated): 4374
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zhe Zheng, MD, PhD; Phone Number: +86 010 88396051; Email: zhengzhe@fuwai.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• Age ≥70 years
• Patients with atrial fibrillation (atrial fibrillation rhythm of at least 30 seconds duration recorded by ECG or Holter within 1 year)
• CHA2DS2-VASc score ≥2 in men and ≥3 in women
• Able to cooperate in signing ICFs

Exclusion criteria：

• Moderate-to-severe mitral stenosis, or prior mechanical valve replacement surgery, or unresected atrial myxoma, or known left ventricular thrombus
• Prior biological valve replacement or valve repair surgery within 6 months
• Left ventricular assist device implantation status
• Severe stroke event within 3 months or any stroke within 14 days Major stroke events were defined as those with a Modified Rankin Scale score of 3-5.

Score 3: moderately disabled, requiring some assistance but walking without assistance; Score 4: severe disability, unable to walk independently, unable to meet their own needs without the help of others; Score 5: severe disability, bedridden, incontinent, requiring ongoing care and attention

• Transient ischemic attack (TIA) occurred within 3 days
• Transient atrial fibrillation due to reversible triggers (e.g., after cardiac surgery, pulmonary embolism, untreated hyperthyroidism)
• Prior or planning to undergo atrial fibrillation catheter ablation, drug cardioversion, electroconversion, or major surgery in 3 months; Prior catheter or surgical ablation > 3 months without atrial fibrillation electrocardiogram records
• Prior or planning to undergo left atrial appendage occlusion
• Active infective endocarditis
• High or increasing risk for bleeding i. Traumatic surgery that has been completed within the last 3 months or is planned within the next 3 months ii. Previous severe intracranial, intraocular, spinal cord, retroperitoneal, or nontraumatic intra-articular hemorrhage.

iii. Gastrointestinal bleeding within the past year iv. Symptomatic or gastroscopic peptic ulcer within the last month v. Hemorrhagic constitution or coagulopathy vi. Difficult-controlled hypertension (180mm Hg systolic and/or 100 mm Hg diastolic)

• Severe renal impairment (estimated creatinine clearance ≤ 15 mL/min)
• Active liver disease

Including but not limited to:

i. Persistent ALT, AST > 2×ULN; ii. TBil > 1.5×ULN; iii. Known active hepatitis A, B or C; iv. Cirrhosis

• Hemoglobin level <100g/L or thrombocytopenia count <100 × 10^9/L
• Having conditions warrant standard-dose or low-dose anticoagulation treatment (non-AF, such as VTE)
• Having conditions warrant warfarin anticoagulation treatment
• Daily dose of aspirin >100mg
• Having received dual antiplatelet therapy or intravenous antiplatelet drugs within 5 days (note: P2Y12 receptor antagonist alone or ≤ 100mg aspirin alone can be enrolled)
• Having received fibrinolysis treatment in 10 days or planning to use fibrinolytic drugs
• Having conditions warrant the following medications: CYP3A4 and P-gp inhibitors (itraconazole, ketoconazole, voriconazole, posaconazole, clarithromycin, erythromycin, fluconazole, ritonavir, dronedarone, etc.), selective serotonin reuptake inhibitors (SSRI)/serotonin norepinephrine reuptake inhibitors (SNRI) drugs (fluoxetine, paroxelin, etc.) CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort, etc.), long-term use of NSAIDs
• Having allergic or adverse reactions to any excipients (including but not limited to lactose, starch, etc.) in rivaroxaban tablets, including but not limited to hereditary lactose or galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption, etc.
• Having diagnosed with malignant tumors within 6 months, or receiving radiotherapy/chemotherapy, with an expected lifespan of no more than 3 years
• Antiphospholipid syndrome
• Having been enrolled in another interventional clinical trial within the past 30 days or at the same time
• Mental disorders, communication barriers, cognitive impairment, or other serious illnesses that may affect the participation in this study
• Known poor adherence to study follow-up or taking study drugs
• Other conditions deemed by the investigator to be inappropriate for enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose rivaroxaban; 15mg q.d. rivaroxaban for 2 years after randomization. The dose should be reduced in the following special conditions: 1. Creatinine clearance <50 mL/min; 2. Body weight ≤60kg; 3. Age ≥80 years old. In the low-dose group, the dose was reduced from the usual 15mg q.d. to 10mg q.d. .	Drug: low-dose rivaroxaban; Rivaroxaban 15mg q.d. (The dose should be reduced to 10mg q.d. in the following special populations: 1. Creatinine clearance <50 mL/min; 2. Body weight ≤60kg; 3. Age ≥80 years old)
Active Comparator: Standard-dose rivaroxaban; 20mg q.d. rivaroxaban for 2 years after randomization. The dose should be reduced in the following special conditions: 1. Creatinine clearance <50 mL/min; 2. Body weight ≤60kg; 3. Age ≥80 years old. In the standard-dose group, the dose was reduced from the 20mg q.d. to 15mg q.d. .	Drug: Standard-dose rivaroxaban; Rivaroxaban 20mg q.d. (The dose should be reduced to 15mg q.d. in the following special populations: 1. Creatinine clearance <50 mL/min; 2. Body weight ≤60kg; 3. Age ≥80 years old)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular and cerebrovascular events(MACCE)	A composite endpoint of clinical events including cardiovascular death, myocardial infarction, stroke, and systemic embolism was firstly recorded after randomization	Through study completion, an estimated average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding events	A composite endpoint of ISTH major bleeding events and clinically relevant non major bleeding events was recorded after randomization	Through study completion, an estimated average of 2 years
Net clinical benefit	A composite endpoint of all-cause death, myocardial infarction, stroke, transient ischemic attack, systemic embolism, ISTH major bleeding events and clinically relevant non major bleeding events after randomization	Through study completion, an estimated average of 2 years
Components of all primary and secondary outcome measures	All-cause death, myocardial infarction, stroke, transient ischemic attack, systemic embolism, ISTH major bleeding events and clinically relevant non major bleeding events after randomization	Through study completion, an estimated average of 2 years

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: October 25, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 31, 2023

Study Record Updates

• Last Update Posted (Actual): July 18, 2024
• Last Update Submitted That Met QC Criteria: July 16, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Cardiovascular Diseases; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: NCRC2022002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No