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): 4306
• 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 6 months)
• CHA2DS2-VASc score ≥2 in men and ≥3 in women

Exclusion criteria：

• Moderate-to-severe mitral stenosis or prior valve replacement surgery
• Severe stroke event within 6 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

• 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. Use of fibrinolytic agents within 48 hours of enrollment vii. Difficult-controlled hypertension (180mm Hg systolic and/or 100 mm Hg diastolic) viii. Diagnosis of malignancy within 6 months or radiotherapy

• Transient atrial fibrillation due to reversible triggers (e.g., after cardiac surgery, pulmonary embolism, untreated hyperthyroidism)
• Catheter ablation or surgery for AF is planned
• Severe renal impairment (estimated creatinine clearance ≤ 30 mL/min)
• Active infective endocarditis
• Active liver disease

Including but not limited to:

i. Persistent ALT, AST, Alk Phos > 2×U; ii. Known active hepatitis C (HCV RNA positive); iii. Active hepatitis B (HBs antigen +, anti-HBc IgM+); iv. Active hepatitis A

• anemia (hemoglobin level <100g/L) or thrombocytopenia (thrombocytopenia count <100 × 10^9/L)
• patients enrolled in another study drug trial within the past 30 days or at the same time
• Patients whose condition warrants standard-dose anticoagulation
• 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 recorded within 2 years after randomization	At 24-month after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Net clinical benefit	All-cause death, myocardial infarction, stroke, transient ischemic attack, systemic embolism, and major bleeding events within 2 years after randomization	At 24-month after randomization

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases

Study record dates

Study Major Dates

• Study Start (Estimated): January 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): October 31, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

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