Short-Term Anticoagulation Versus Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure

Phase 4

Recruiting

• Conditions: Bleeding; Stroke; Left Atrial Appendage Closure; TIA; Thrombosis
• Interventions: Drug: Rivaroxaban, dabigatran, apixaban, or edoxaban; Drug: Clopidogrel -75 mg/day; Drug: Low dose aspirin -80 to 125 mg/day-

• Registration Number: NCT03568890
• Lead Sponsor: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Brief Summary

The objective of the study is to compare short-term (8 weeks) anticoagulation therapy (DOAC) vs. antiplatelet therapy for the prevention of device thrombosis following transcatheter LAAC.

Detailed Description

Transcatheter left atrial appendage closure (LAAC) has emerged as an alternative to anticoagulation for preventing thromboembolic events in patients with atrial fibrillation. Whereas most complications associated with LAAC have decreased over time, the occurrence of device thrombosis remains a concern, with an incidence of 1 to 17%. Antithrombotic therapy for preventing device thrombosis following LAAC has evolved empirically, with antiplatelet therapy being the most commonly prescribed treatment. However, the rates of device thrombosis post-LAAC remain relatively high and have not decreased over time despite of increasing operator/center experience and the arrival of newer generation devices. This is of particular concern if we consider that LAAC is a preventive treatment. Experimental and mechanistic studies have suggested enhanced thrombin generation (and not platelet activation) within the days-weeks following the procedure as the most important mechanism involved in device thrombosis and appropriate short-term anticoagulation therapy with DOAC should translate into a significant reduction in the rate of device thrombosis post-LAAC.

Therefore, the objective of the study is to compare short-term (60 days) anticoagulation therapy (DOAC) vs. antiplatelet therapy for the prevention of device thrombosis following transcatheter LAAC.

It is estimated that 350 patients will take part in the study.

Update: A blinded interim analysis was performed with the analysis of clinical and TEE (central echo core lab) data from the initial 155 patients included in the study. Based on the results of the interim analysis, and considering the total number of events and the high rate (20%) of patients with either early cessation of the allocated treatment (before the 60-day TEE examination) or missing TEE at 60 days, it was decided to increase the sample size by 160 patients up to a total of 510 patients. This would ensure to include at least 350 patients with a TEE examination performed while receiving the allocated antithrombotic treatment.

Study Timeline

• Study First Submitted: 2018-06-14
• Study First Submitted QC: 2018-06-22
• Study First Posted: 2018-06-26
• Study Start: 2018-09-01
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-18
• Last Update Posted: 2023-12-22
• Primary Completion: 2025-12-01
• Study Completion: 2026-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 510

Inclusion Criteria

• Successful transcatheter LAAC with any approved device
• Age≥18 years old

Exclusion Criteria

• Absolute contraindications for anticoagulation therapy
• Absolute contraindications for antiplatelet therapy
• End-stage renal disease (CrCl <15 ml/min)
• Recent percutaneous revascularization with drug-eluting stents requiring dual antiplatelet therapy
• Prior intracranial hemorrhage
• Contraindications for TEE
• Severe pericardial effusion within the first 24 hrs following LAAC
• Major/life-threatening bleeding event within the month prior to LAAC
• Multiple bleeding events (minor or major) within the month prior to LAAC
• Major/life-threatening bleeding within the first 24 hrs following LAAC

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anticoagulation therapy	Rivaroxaban, dabigatran, apixaban, or edoxaban	Direct oral anticoagulants (rivaroxaban, dabigatran, apixaban, or edoxaban; with dosage according to guideline recommendations) for 60 days.
Antiplatelet therapy	Clopidogrel -75 mg/day	Dual antiplatelet therapy with clopidogrel -75 mg/day- and low dose aspirin -80 to 125 mg/day for 60 days.
Antiplatelet therapy	Low dose aspirin -80 to 125 mg/day-	Dual antiplatelet therapy with clopidogrel -75 mg/day- and low dose aspirin -80 to 125 mg/day for 60 days.

Primary Outcome Measures

Name	Time	Method
Device thrombosis (efficacy outcome)	60 days after LAAC	Evaluated by TEE
Combined outcome of all-cause mortality, bleeding, stroke, or Device thrombosis (Safety outcome)	60 days after LAAC	Clinically evaluated and diagnosed by the center investigators and determining a treatment change.

Secondary Outcome Measures

Name	Time	Method
Ischemic events	60 days, 12-month, 2-year, 3-year, 4-year and 5-year follow-up	Stroke, TIA
Device thrombosis	12 months after LAAC	Evaluated by TEE or computed tomography
Bleeding events	60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up
Major or Life-threatening bleeding events	60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up
Mortality	60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up	All cause mortality

Trial Locations

Locations (1)

Josep Rodes-Cabau; 🇨🇦 Quebec, Canada