Low-dose NOAC Versus GDMT After LAAO (RECORD-III)

Low-dose Rivaroxaban Monotherapy Versus Guideline Determined Medication Therapy After Left Atrial Appendage Occlusion: a Randomized, Open-label, Multicentre, Superiority Trial

The increased risk of Atrial fibrillation (AF) regarding thromboembolic stroke is predominantly due to the formation and embolization of clots from within the left atrial appendage (LAA). Percutaneous left atrial appendage occlusion (LAAO) is a nonpharmacological strategy for stroke prevention in patients with AF. Data from randomized trials, including PROTECT-AF, PREVAIL, and Prague-17, have suggested that LAAO has comparable efficacy to warfarin or NOACs. Considering these results, LAAO was recommended by the American College of Cardiology (ACC) and European Society of Cardiology (ESC) guidelines as a non-pharmacological stroke prevention strategy for patients with NVAF who have contraindications or are unsuitable for OAC.

The PROTECT-AF and PREVAIL trials stipulated the use of standardized antithrombotic medications which were designed to minimize the risk of stroke, systemic embolism, or device-related thrombosis. This antithrombotic strategy was subsequently endorsed by the guidelines, briefly, patients with LAAO were discharged on warfarin and aspirin for 45 days post-LAAO, if there was no leak or a leak ≤5 mm under transesophageal echocardiography (TEE) at 45-day follow-up, antithrombotic strategies shall switch to dual antiplatelet therapy (DAPT) until 6 months post-LAAO, and then aspirin thereafter.

Although LAAO was recommended by medical societies, previous patient-level meta-analyses have implied that compared with oral anticoagulation, LAAO had significantly more ischemic strokes, suggesting the inability of LAAO to prevent an ischemic stroke from sources beyond LAA. Will a combined strategy of LAAO and OAC further reduce the risk of stroke? The investigators hypothesized that a long-term low dose-Rivaroxaban (10mg daily) post-LAAO might be a potent supplement to the residue risk of ischemic stroke.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Rivaroxaban 15mg; Drug: Rivaroxaban 10mg; Drug: Rivaroxaban 2.5mg; Drug: Aspirin 100mg; Drug: Clopidogrel 75mg

• Study Type: Interventional
• Enrollment (Estimated): 4220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chao Gao, M.D., Ph.D.; Phone Number: +86-18629551066; Email: woshigaochao@gmail.com
• Study Contact Backup: Name: Ruining Zhang, BSc; Phone Number: +86-15802990370; Email: ruining-zhang@qq.com

Study Locations

• China
  • Shannxi
    • Xi'an, Shannxi, China, 710032
      • Recruiting
      • Ling Tao
      • Contact: Chao Gao, M.D., Ph.D.; Phone Number: +8618629551066; Email: woshigaochao@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Non-valvular atrial fibrillation (NVAF) patients with successful left atrial appendage occlusion (LAAO)
2. Eligible for guideline-directed anti-thrombotic therapy
3. Able to understand and provide informed consent and comply with all study medications

Exclusion Criteria:

1. Under the age of 18
2. Unable to give informed consent or currently participating in another trial and not yet at its primary endpoint
3. Patient is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential according to local practice)
4. Concurrent medical condition with a life expectancy of less than two years
5. Haemodynamical unstable
6. Known contraindication to medications such as heparin, antiplatelet or anticoagulation drugs, or contrast
7. Peridevice leak > 5mm as assessed immediately after LAAO or any other procedure-related complications
8. Comorbidities other than atrial fibrillation that required long term use of anticoagulation (such as implanted mechanical valve)
9. Percutaneous coronary intervention (PCI) within 1 year.
10. The patient had or is planning to have any cardiac or non-cardiac interventional or surgical procedure within 30 days prior to or 60 days after the WATCHMAN device implant (e.g., PCI, cardioversion, cardiac surgery)
11. Ongoing overt bleeding
12. Previous stroke/TIA within 30 days of enrolment
13. Symptomatic carotid artery disease
14. Severe renal insufficiency (CrCl≤30ml/min/1.73m2)

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 novel oral anti-coagulation (NOAC)-based anti-thrombotic therapy; HAS-BLED<3: Rivaroxaban 15 mg QD for 3 months, followed by Rivaroxaban 10 mg QD indefinitely HAS-BLED≥3: Rivaroxaban 10 mg QD for 3 months, followed by Rivaroxaban 2.5 mg bid indefinitely	Drug: Rivaroxaban 15mg; QD; Drug: Rivaroxaban 10mg; QD; Drug: Rivaroxaban 2.5mg; B.I.D
Active Comparator: Guideline determined medication therapy (GDMT); HAS-BLED<3: Rivaroxaban 15 mg QD + Aspirin 100mg QD for 3 months, then Aspirin 100mg QD indefinitely HAS-BLED≥3: Aspirin 100mg QD + Clopidogrel 75mg QD for 3 months, then Aspirin 100mg QD indefinitely	Drug: Rivaroxaban 15mg; QD; Drug: Aspirin 100mg; QD; Drug: Clopidogrel 75mg; QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of the composite endpoint of any death, any stroke, systemic embolism, and The Bleeding Academic Research Consortium (BARC)-defined 3 or 5 bleeding events	24 months post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of the composite endpoint of any death, any stroke, systemic embolism, and BARC defined 3 or 5 bleeding events		45 days, 6, 12 months (Time-to-event)
Rate of the composite endpoint of any death, any stroke, systemic embolism		45 days, 6, 12, 24 months (Time-to-event)
Rate of the BARC type 3 or 5 bleeding events		45 days, 6, 12, 24 months (Time-to-event)
Rate of the composite endpoint of any death, any stroke, systemic embolism, myocardial infarction (MI)		45 days, 6, 12, 24 months (Time-to-event)
Rate of any death		45 days, 6, 12, 24 months (Time-to-event)
Rate of any stroke		45 days, 6, 12, 24 months (Time-to-event)
Rate of systemic embolism		45 days, 6, 12, 24 months (Time-to-event)
Rate of myocardial infarction (MI)		45 days, 6, 12, 24 months (Time-to-event)
Rate of BARC type 2, 3 or 5 bleeding events		45 days, 6, 12, 24 months (Time-to-event)
Rate of BARC type 2 bleeding events		45 days, 6, 12, 24 months (Time-to-event)
Rate of BARC type 3 bleeding events		45 days, 6, 12, 24 months (Time-to-event)
Rate of BARC type 5 bleeding events		45 days, 6, 12, 24 months (Time-to-event)
Rate of GUSTO defined major bleeding and/or minor bleeding	Global Use of Strategies to Open Occluded Arteries, (GUSTO) defined major bleeding and/or minor bleeding	45 days, 6, 12, 24 months (Time-to-event)
Rate of TIMI defined major bleeding and/or minor bleeding	Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding and/or minor bleeding	45 days, 6, 12, 24 months (Time-to-event)
Rate of ISTH defined major bleeding and/or clinically relevant minor bleeding	International Society on Thrombosis and Haemostasis (ISTH) defined major bleeding and/or clinically relevant minor bleeding	45 days, 6, 12, 24 months (Time-to-event)
Rate of patient adherence to allocated medication	Adherence is defined as the participant who uses the medication strategies in this trial achieving 80% of the time on the therapeutic range	45 days, 6, 12, 24 months (Binary)
Scores of the National Institutes of Health Stroke Scale (NIHSS) questionnaire	The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.	45 days, 6, 12, 24 months (Continuous)
Scores of the Modified Rankin Scale (mRS)	The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials.	45 days, 6, 12, 24 months (Continuous)
Scores of the 5-level EQ-5D version (EQ-5D-5L) questionnaire	The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.	45 days, 6, 12, 24 months (Continuous)

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Study Chair: Ling Tao, M.D., Ph.D., Xijing Hospital; Study Chair: Chao Gao, M.D., Ph.D., Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: June 28, 2023
• First Submitted That Met QC Criteria: July 24, 2023
• First Posted (Actual): July 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; Left atrial appendage occlusion; Anti-coagulation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Aspirin; Clopidogrel; Rivaroxaban
• Other Study ID Numbers: RECORD-III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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