Clinical trial NCT05960721: Low-dose NOAC Versus GDMT After LAAO
Official title: Low-dose Rivaroxaban Monotherapy Versus Guideline Determined Medication Therapy After Left Atrial Appendage Occlusion: a Randomized, Open-label, Multicentre, Superiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Keywords: Left atrial appendage occlusion
Anti-coagulation
Atrial Fibrillation
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2023-07-27
Enrollment: 4220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: 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
timeFrame: 24 months post randomization
Secondary outcomes:
measure: Rate of the composite endpoint of any death, any stroke, systemic embolism, and BARC defined 3 or 5 bleeding events
timeFrame: 45 days, 6, 12 months (Time-to-event)
measure: Rate of the composite endpoint of any death, any stroke, systemic embolism
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of the BARC type 3 or 5 bleeding events
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of the composite endpoint of any death, any stroke, systemic embolism, myocardial infarction (MI)
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of any death
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of any stroke
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of systemic embolism
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of myocardial infarction (MI)
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of BARC type 2, 3 or 5 bleeding events
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of BARC type 2 bleeding events
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of BARC type 3 bleeding events
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of BARC type 5 bleeding events
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of GUSTO defined major bleeding and/or minor bleeding
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of TIMI defined major bleeding and/or minor bleeding
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of ISTH defined major bleeding and/or clinically relevant minor bleeding
timeFrame: 45 days, 6, 12, 24 months (Time-to-event)
measure: Rate of patient adherence to allocated medication
timeFrame: 45 days, 6, 12, 24 months (Binary)
measure: Scores of the National Institutes of Health Stroke Scale (NIHSS) questionnaire
timeFrame: 45 days, 6, 12, 24 months (Continuous)
measure: Scores of the Modified Rankin Scale (mRS)
timeFrame: 45 days, 6, 12, 24 months (Continuous)
measure: Scores of the 5-level EQ-5D version (EQ-5D-5L) questionnaire
timeFrame: 45 days, 6, 12, 24 months (Continuous)
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Ling Tao
state: Shannxi
Study officials:
affiliation: Xijing Hospital
name: Ling Tao, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: Xijing Hospital
name: Chao Gao, M.D., Ph.D.
role: STUDY_CHAIR
References: