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

Stroke Clinical Trial

— ANDES  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03568890
• Other study ID #: ANDES
• Status: Recruiting
• Phase: Phase 4
• Start date: September 1, 2018
• Est. completion date: September 1, 2026

Study information

• Verified date: December 2023
• Source: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
• Contact: Josep Rodes-Cabau, MD
• Phone: 418-656-8711
• Email: josep.rodes[@]criucpq.ulaval.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 510
• Est. completion date: September 1, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bleeding
• Left Atrial Appendage Closure
• Stroke
• Thrombosis
• TIA

Intervention

Drug:
• Rivaroxaban, dabigatran, apixaban, or edoxaban
Duration of treatment: 60 days
• Clopidogrel -75 mg/day
Duration of treatment: 60 days
• Low dose aspirin -80 to 125 mg/day-
Duration of treatment: 60 days

Locations

Country	Name	City	State
Canada	Josep Rodes-Cabau	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Country where clinical trial is conducted

Canada, 

References & Publications (16)

Asmarats L, Rodes-Cabau J. Percutaneous Left Atrial Appendage Closure: Current Devices and Clinical Outcomes. Circ Cardiovasc Interv. 2017 Nov;10(11):e005359. doi: 10.1161/CIRCINTERVENTIONS.117.005359. — View Citation

Bass JL. Transcatheter occlusion of the left atrial appendage--experimental testing of a new Amplatzer device. Catheter Cardiovasc Interv. 2010 Aug 1;76(2):181-5. doi: 10.1002/ccd.22536. — View Citation

Fauchier L, Cinaud A, Brigadeau F, Lepillier A, Pierre B, Abbey S, Fatemi M, Franceschi F, Guedeney P, Jacon P, Paziaud O, Venier S, Deharo JC, Gras D, Klug D, Mansourati J, Montalescot G, Piot O, Defaye P. Device-Related Thrombosis After Percutaneous Lef — View Citation

Jalal Z, Dinet ML, Combes N, Pillois X, Renou P, Sibon I, Iriart X, Thambo JB. Percutaneous left atrial appendage closure followed by single antiplatelet therapy: Short- and mid-term outcomes. Arch Cardiovasc Dis. 2017 Apr;110(4):242-249. doi: 10.1016/j.a — View Citation

January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; ACC/AHA Task Force Members. 2014 AHA/ACC/HRS guideline for the manageme — View Citation

Kar S, Hou D, Jones R, Werner D, Swanson L, Tischler B, Stein K, Huibregtse B, Ladich E, Kutys R, Virmani R. Impact of Watchman and Amplatzer devices on left atrial appendage adjacent structures and healing response in a canine model. JACC Cardiovasc Inte — View Citation

Lempereur M, Aminian A, Freixa X, Gafoor S, Kefer J, Tzikas A, Legrand V, Saw J. Device-associated thrombus formation after left atrial appendage occlusion: A systematic review of events reported with the Watchman, the Amplatzer Cardiac Plug and the Amule — View Citation

Lopez-Lopez JA, Sterne JAC, Thom HHZ, Higgins JPT, Hingorani AD, Okoli GN, Davies PA, Bodalia PN, Bryden PA, Welton NJ, Hollingworth W, Caldwell DM, Savovic J, Dias S, Salisbury C, Eaton D, Stephens-Boal A, Sofat R. Oral anticoagulants for prevention of s — View Citation

Main ML, Fan D, Reddy VY, Holmes DR, Gordon NT, Coggins TR, House JA, Liao L, Rabineau D, Latus GG, Huber KC, Sievert H, Wright RF, Doshi SK, Douglas PS. Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial — View Citation

O'Hara C, O'Hara GE, Jacques F, Champagne J, Lemyre M, Charbonneau L, O'Connor K, Bernier M, Beaudoin J, Rodes-Cabau J, Paradis JM. Run With the Hare and Hunt With the Hounds: Watchman Device Surgical Resection in the Setting of Recurrent Device Related T — View Citation

Rodes-Cabau J, O'Hara G, Paradis JM, Bernier M, Rodriguez-Gabella T, Regueiro A, O'Connor K, Beaudoin J, Puri R, Cote M, Champagne J. Changes in Coagulation and Platelet Activation Markers Following Transcatheter Left Atrial Appendage Closure. Am J Cardio — View Citation

Rodriguez-Gabella T, Nombela-Franco L, Regueiro A, Jimenez-Quevedo P, Champagne J, O'Hara G, Bernier M, Macaya C, Rodes-Cabau J. Single Antiplatelet Therapy Following Left Atrial Appendage Closure in Patients With Contraindication to Anticoagulation. J Am — View Citation

Saw J, Tzikas A, Shakir S, Gafoor S, Omran H, Nielsen-Kudsk JE, Kefer J, Aminian A, Berti S, Santoro G, Nietlispach F, Moschovitis A, Cruz-Gonzalez I, Stammen F, Tichelbacker T, Freixa X, Ibrahim R, Schillinger W, Meier B, Sievert H, Gloekler S. Incidence — View Citation

Schwartz RS, Holmes DR, Van Tassel RA, Hauser R, Henry TD, Mooney M, Matthews R, Doshi S, Jones RM, Virmani R. Left atrial appendage obliteration: mechanisms of healing and intracardiac integration. JACC Cardiovasc Interv. 2010 Aug;3(8):870-7. doi: 10.101 — View Citation

Tzikas A, Shakir S, Gafoor S, Omran H, Berti S, Santoro G, Kefer J, Landmesser U, Nielsen-Kudsk JE, Cruz-Gonzalez I, Sievert H, Tichelbacker T, Kanagaratnam P, Nietlispach F, Aminian A, Kasch F, Freixa X, Danna P, Rezzaghi M, Vermeersch P, Stock F, Stolco — View Citation

Verheugt FW, Granger CB. Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs. Lancet. 2015 Jul 18;386(9990):303-10. doi: 10.1016/S0140-6736(15)60245-8. Epub 2015 Mar 14. Erratum In: Lancet. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Device thrombosis (efficacy outcome)	Evaluated by TEE	60 days after LAAC
Primary	Combined outcome of all-cause mortality, bleeding, stroke, or Device thrombosis (Safety outcome)	Clinically evaluated and diagnosed by the center investigators and determining a treatment change.	60 days after LAAC
Secondary	Device thrombosis	Evaluated by TEE or computed tomography	12 months after LAAC
Secondary	Ischemic events	Stroke, TIA	60 days, 12-month, 2-year, 3-year, 4-year and 5-year follow-up
Secondary	Bleeding events		60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up
Secondary	Major or Life-threatening bleeding events		60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up
Secondary	Mortality	All cause mortality	60 days and 12-month, 2-year, 3-year, 4-year and 5-year follow-up