CLOT-LESS - CLOsure Tailored: LEss Antithrombotic Strategy After LAAC for Stroke Prevention

NCT07575867 | Recruiting DMC

• 1 other identifier: 03-03/26
• Study Type: observational
• Target: 464
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, non-randomized, observational cohort study conducted at the FSBI "NMRC TPM" of the Ministry of Healthcare of the Russian Federation. Left atrial appendage closure (LAAC) has been shown to be non-inferior to oral anticoagulation for preventing cardioembolic events in patients with atrial fibrillation. However, the optimal post-procedural antithrombotic regimen following LAAC remains unclear, with no consensus on evidence-based therapy. Given current trends in cardiology favoring reduced-intensity antithrombotic strategies, this study aims to contribute to the evidence base by evaluating whether LAAC followed by reduced-dose apixaban (2.5 mg BID) for 3 months with subsequent complete withdrawal of antithrombotic therapy is superior to long-term standard-dose DOAC therapy in patients with non-valvular atrial fibrillation.

Conditions

Atrial Fibrillation; Stroke Prevention in Patients With Atrial Fibrillation; Left Atrial Appendage Closure; Hemorrhage; Anticoagulants / Administration & Dosage; Reduced-dose Apixaban; Thromboembolism

Keywords

atrial fibrillation; left atrial appendage closure; anticoagulants; reduced dose apixaban

Outcome Measures

Primary Outcomes (1)

• Composite of major adverse events

  Composite endpoint including: bleeding events (BARC type ≥3), all-cause death, ischemic stroke, systemic embolism, device-related thrombosis (DRT), and peri-device leak (\>3 mm)

  36 months from enrollment

Secondary Outcomes (6)

• Major bleeding events

  36 months from enrollment

• All-cause mortality

  36 months from enrollment

• Ischemic stroke

  36 months from enrollment

• Systemic embolism

  36 months from enrollment

• Device-related thrombosis

  36 months from enrollment

Study Arms (2)

LAAC with reduced-dose anticoagulation

Patients undergoing left atrial appendage closure (LAAC) with Watchman FLX or Amplatzer Amulet devices, followed by reduced-dose apixaban (2.5 mg BID) for 3 months with subsequent complete withdrawal of antithrombotic therapy

Device: Left Atrial Appendage Closure; Drug: Apixaban 2.5 mg BID

Standard-dose DOAC

Patients receiving long-term standard-dose direct oral anticoagulant (DOAC) therapy per current guidelines

Drug: Standard-dose DOAC

Interventions

Left Atrial Appendage Closure DEVICE

Percutaneous left atrial appendage closure using Watchman FLX (Boston Scientific) or Amplatzer Amulet (Abbott) devices

Also known as: LAAC

LAAC with reduced-dose anticoagulation

Apixaban 2.5 mg BID DRUG

Reduced-dose apixaban 2.5 mg BID for 3 months post-LAAC, followed by complete withdrawal of antithrombotic therapy

LAAC with reduced-dose anticoagulation

Standard-dose DOAC DRUG

Standard-dose DOAC therapy (e.g., apixaban 5 mg BID, rivaroxaban 20 mg daily, or other DOAC per physician discretion) continued for the duration of follow-up

Standard-dose DOAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population comprises adults with documented non-valvular atrial fibrillation who require stroke prevention therapy. Two distinct cohorts will be enrolled: Cohort 1 (LAAC group): Patients with non-valvular atrial fibrillation and elevated thromboembolic risk who have relative or absolute contraindications to long-term oral anticoagulation, history of bleeding complications on anticoagulation, or patient preference for a non-pharmacological stroke prevention strategy. These patients will undergo percutaneous left atrial appendage closure. Cohort 2 (Control group): Patients with non-valvular atrial fibrillation and elevated thromboembolic risk who are appropriate candidates for and willing to continue long-term standard-dose direct oral anticoagulant therapy. Both cohorts will be recruited from the same institution during the same time period to minimize selection bias related to temporal trends in clinical practice.

You may qualify if:

• Age ≥18 years;
• Documented nonvalvular AF (≥30 seconds on ECG within previous 12 months);
• CHA2DS2-VASc score ≥3 for women and ≥2 for men;
• Signed informed consent to participate in the study;

You may not qualify if:

• Active indication for anticoagulation OTHER than atrial fibrillation at the time of enrollment and/or the predicted/unpredicted occurrence of such indications during the entire study period (e.g., mechanical valve, acute VTE, recent PE requiring \>3 months anticoagulation);
• Inability to tolerate at least 3 months of apixaban therapy (for LAAC arm);
• The presence of mechanical prosthetic heart valves, mitral stenosis of severe or moderate degree;
• Active DVT requiring anticoagulation;
• Congenital or acquired haemostasis disorders, rheumatic heart disease or recurrent deep vein thrombosis;
• Left ventricular ejection fraction (LVEF) \< 30%;
• Glomerular filtration rate (GFR) \< 30 ml/min (stage IV or V chronic kidney disease) or dialysis patient;
• Severe liver failure, including cirrhosis and Child-Pugh Class C/D;
• NYHA class IV congestive heart failure;
• The patient had a myocardial infarction - MI with or without ST segment elevation (STEMI, NSTEMI) with or without intervention, within 30 days before LAAC;
• The patient had a stroke (of any cause, ischemic or hemorrhagic) within 30 days before LAAC;
• Intracardiac thrombus before LAAC;
• Major bleeding according to BARC criteria (type 3 and higher) within 30 days before LAAC or before randomization;
• Amyloid cardiomyopathy;
• Platelet count \< 100,000 x 109/l;

Sponsors & Collaborators

• National Medical Research Center for Therapy and Preventive Medicine: lead

Study Sites (1)

Federal State Budgetary Institution National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthсare of the Russian Federation

Moscow, 101990, Russia

RECRUITING

Related Publications (13)

• Potpara T, Grygier M, Hausler KG, Nielsen-Kudsk JE, Berti S, Genovesi S, Marijon E, Boveda S, Tzikas A, Boriani G, Boersma LVA, Tondo C, De Potter T, Lip GYH, Schnabel RB, Bauersachs R, Senzolo M, Basile C, Bianchi S, Osmancik P, Schmidt B, Landmesser U, Dohner W, Hindricks G, Kovac J, Camm AJ. Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper. Europace. 2024 Mar 30;26(4):euae035. doi: 10.1093/europace/euae035. Erratum In: Europace. 2024 May 2;26(5):euae142. doi: 10.1093/europace/euae142.

  PMID: 38291925 BACKGROUND

• Continisio S, Montonati C, Angelini F, Bocchino PP, Carbonaro C, Giacobbe F, Dusi V, De Filippo O, Ielasi A, Giannino G, Boldi E, Fabris T, D'Ascenzo F, De Ferrari GM, Tarantini G. Single versus dual antiplatelet therapy following percutaneous left atrial appendage closure-A systematic review and meta-analysis. Eur J Clin Invest. 2024 Aug;54(8):e14209. doi: 10.1111/eci.14209. Epub 2024 Apr 10.

  PMID: 38597271 BACKGROUND

• Kramer A, Korsholm K, Nielsen-Kudsk JE. Single antiplatelet therapy following Amplatzer left atrial appendage occlusion. EuroIntervention. 2024 Mar 4;20(5):e301-e311. doi: 10.4244/EIJ-D-23-00684.

  PMID: 38436367 BACKGROUND

• Li X, Jin Q, Yao Y, Zhang X, Lv Q. Clinical Effectiveness and Safety Comparison between Reduced Rivaroxaban Dose and Dual Antiplatelet Therapy for Nonvalvular Atrial Fibrillation Patients Following Percutaneous Left Atrial Appendage Closure: A Prospective Observational Study. Rev Cardiovasc Med. 2023 Nov 27;24(11):335. doi: 10.31083/j.rcm2411335. eCollection 2023 Nov.

  PMID: 39076450 BACKGROUND

• Cepas-Guillen PL, Flores-Umanzor E, Regueiro A, Brugaletta S, Ibanez C, Sanchis L, Sitges M, Rodes-Cabau J, Sabate M, Freixa X. Low Dose of Direct Oral Anticoagulants after Left Atrial Appendage Occlusion. J Cardiovasc Dev Dis. 2021 Oct 28;8(11):142. doi: 10.3390/jcdd8110142.

  PMID: 34821695 BACKGROUND

• Faroux L, Cruz-Gonzalez I, Arzamendi D, Freixa X, Nombela-Franco L, Peral V, Caneiro-Queija B, Mangieri A, Trejo-Velasco B, Asmarats L, Regueiro A, McInerney A, Mas-Llado C, Estevez-Loureiro R, Laricchia A, O'Hara G, Rodes-Cabau J. Short-term direct oral anticoagulation or dual antiplatelet therapy following left atrial appendage closure in patients with relative contraindications to chronic anticoagulation therapy. Int J Cardiol. 2021 Jun 15;333:77-82. doi: 10.1016/j.ijcard.2021.02.054. Epub 2021 Feb 27.

  PMID: 33647365 BACKGROUND

• Bergmann MW, Betts TR, Sievert H, Schmidt B, Pokushalov E, Kische S, Schmitz T, Meincke F, Stein KM, Boersma LVA, Ince H. Safety and efficacy of early anticoagulation drug regimens after WATCHMAN left atrial appendage closure: three-month data from the EWOLUTION prospective, multicentre, monitored international WATCHMAN LAA closure registry. EuroIntervention. 2017 Sep 20;13(7):877-884. doi: 10.4244/EIJ-D-17-00042.

  PMID: 28606886 BACKGROUND

• Freixa X, Cruz-Gonzalez I, Cepas-Guillen P, Millan X, Antunez-Muinos P, Flores-Umanzor E, Asmarats L, Regueiro A, Lopez-Tejero S, Li CP, Sanchis L, Rodes-Cabau J, Arzamendi D. Low-Dose Direct Oral Anticoagulation vs Dual Antiplatelet Therapy After Left Atrial Appendage Occlusion: The ADALA Randomized Clinical Trial. JAMA Cardiol. 2024 Oct 1;9(10):922-926. doi: 10.1001/jamacardio.2024.2335.

  PMID: 39110427 BACKGROUND

• Vignali L, Gurgoglione FL, Barocelli F, Cattabiani MA, Solinas E, Maini A, Tadonio I, Benatti G, Pela G, Coli S, Ardissino D, Niccoli G. Looking for optimal antithrombotic strategy after transcatheter left atrial appendage occlusion: a real-world comparison of different antiplatelet regimens. Int J Cardiol. 2023 Jan 15;371:92-99. doi: 10.1016/j.ijcard.2022.09.066. Epub 2022 Sep 29.

  PMID: 36181948 BACKGROUND

• Zhou Q, Liu X, Gu ZC, Yang X, Huang XH, Wu YZ, Tao YY, Wei M. Short-term antiplatelet versus anticoagulant therapy after left atrial appendage closure: a systematic review and meta-analysis. J Thromb Thrombolysis. 2024 Feb;57(2):194-203. doi: 10.1007/s11239-023-02919-2. Epub 2024 Jan 5.

  PMID: 38180590 BACKGROUND

• Wazni OM, Saliba WI, Nair DG, Marijon E, Schmidt B, Hounshell T, Ebelt H, Skurk C, Oza S, Patel C, Kanagasundram A, Sadhu A, Sundaram S, Osorio J, Mark G, Gupta M, DeLurgio DB, Olson J, Nielsen-Kudsk JE, Boersma LVA, Healey JS, Phillips KP, Asch FM, Wolski K, Roy K, Christen T, Sutton BS, Stein KM, Reddy VY; OPTION Trial Investigators. Left Atrial Appendage Closure after Ablation for Atrial Fibrillation. N Engl J Med. 2025 Apr 3;392(13):1277-1287. doi: 10.1056/NEJMoa2408308. Epub 2024 Nov 16.

  PMID: 39555822 BACKGROUND

• Raffo C, Greco A, Capodanno D. Antithrombotic therapy after left atrial appendage occlusion. Expert Rev Cardiovasc Ther. 2025 Apr;23(4):141-152. doi: 10.1080/14779072.2025.2486154. Epub 2025 Apr 3.

  PMID: 40151884 BACKGROUND

• Osmancik P, Herman D, Neuzil P, Hala P, Taborsky M, Kala P, Poloczek M, Stasek J, Haman L, Branny M, Chovancik J, Cervinka P, Holy J, Kovarnik T, Zemanek D, Havranek S, Vancura V, Peichl P, Tousek P, Lekesova V, Jarkovsky J, Novackova M, Benesova K, Widimsky P, Reddy VY; PRAGUE-17 Trial Investigators. 4-Year Outcomes After Left Atrial Appendage Closure Versus Nonwarfarin Oral Anticoagulation for Atrial Fibrillation. J Am Coll Cardiol. 2022 Jan 4;79(1):1-14. doi: 10.1016/j.jacc.2021.10.023. Epub 2021 Nov 5.

  PMID: 34748929 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation; Hemorrhage; Thromboembolism

Interventions

Left Atrial Appendage Closure; apixaban; BID protein, human; N(4)-oleylcytosine arabinoside

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis; Vascular Diseases

Intervention Hierarchy (Ancestors)

Cardiac Catheterization; Catheterization; Therapeutics; Investigative Techniques

Study Officials

• Karapet Davtyan, Professor

  Federal State Budgetary Institution National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthсare of the Russian Federation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timofey Brontveyn, Medical doctor

CONTACT

+79150579995; tbrontveyn.md@gmail.com

Karapet Davtyan, Professor

CONTACT

+79037758779; kdavtyan@gnicpm.ru

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2026
• First Posted: May 8, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2032
• Study Completion (Estimated): April 1, 2032
• Last Updated: May 8, 2026

Record last verified: 2026-05

Locations

RU (1)