- ICH GCP
- Registr klinických studií v USA
- Klinická studie NCT07575867
CLOT-LESS - CLOsure Tailored: LEss Antithrombotic Strategy After LAAC for Stroke Prevention (CLOT-LESS)
Přehled studie
Postavení
Podmínky
Detailní popis
This is a prospective, non-randomized, observational cohort study enrolling patients with non-valvular atrial fibrillation (NVAF).
Participants will be assigned to one of two groups based on clinical indication. LAAC group: Patients with NVAF undergoing left atrial appendage closure (LAAC) who will receive reduced-dose apixaban (2.5 mg BID) for 3 months, followed by complete withdrawal of antithrombotic therapy. The criterion for anticoagulation discontinuation will be a satisfactory result on transesophageal echocardiography (TEE) or cardiac computed tomography (CT) at 3 months post-implantation, confirming adequate device sealing without significant peri-device leak or device-related thrombosis. Participants will undergo additional TEE or cardiac CT at 6 and 12 months after the procedure and will be followed up by telephone at 18, 24, 30, and 36 months after enrollment.
Control group: Patients with NVAF indicated for long-term oral anticoagulation will receive standard full-dose direct oral anticoagulant (DOAC) therapy. Participants in the control group will be followed up by telephone at 3, 6, 12, 18, 24, 30, and 36 months after enrollment.
Observation period: 36 months. Devices used for LAAC will include the Watchman FLX (Boston Scientific, St. Paul, Minnesota, USA) and the Amplatzer Amulet (Abbott, St. Paul, Minnesota, USA).
Primary endpoint: A composite of major bleeding (BARC type ≥3), all-cause mortality, ischemic stroke, systemic embolism, device-related thrombosis (DRT), and significant peri-device leak over 36 months of follow-up.
Secondary endpoints: Individual components of the primary composite endpoint over 36 months of follow-up.
Propensity score matching will be used to create balanced comparison groups for statistical analysis, adjusting for baseline differences between cohorts.
Typ studie
Zápis (Odhadovaný)
Kontakty a umístění
Studijní kontakt
- Jméno: Timofey Brontveyn, Medical doctor
- Telefonní číslo: +79150579995
- E-mail: tbrontveyn.md@gmail.com
Studijní záloha kontaktů
- Jméno: Karapet Davtyan, Professor
- Telefonní číslo: +79037758779
- E-mail: kdavtyan@gnicpm.ru
Studijní místa
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Moscow, Rusko, 101990
- Nábor
- Federal State Budgetary Institution National Medical Research Center for Therapy and Preventive Medicine of the Ministry of Healthсare of the Russian Federation
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Kontakt:
- Timofey Brontveyn, Medical doctor
- Telefonní číslo: +79150579995
- E-mail: tbrontveyn.md@gmail.com
-
Kontakt:
- Karapet Davtyan, Professor
- Telefonní číslo: +79037758779
- E-mail: kdavtyan@gnicpm.ru
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Metoda odběru vzorků
Studijní populace
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.
Popis
Inclusion Criteria:
- 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;
Exclusion Criteria:
- 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);
- Indications for antiplatelet therapy or therapy with P2Y12 inhibitors at the time of inclusion and/or the predicted/unpredicted occurrence of such indications during the entire study period;
- 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;
- The patient participates in another study, with the exception of observational studies without therapeutic interventions;
- Pregnant or breast-feeding patients, patients planning pregnancy during the study period;
- The LAAC procedure was unsuccessful or interrupted for technical reasons;
- PDL (peridevice leak) ≥ 3 mm;
- Contraindications for one of the treatment regimens prescribed by the study protocol (including allergic reactions);
- Planned cardiac or non-cardiac surgical procedure within 30 days before or 90 days after LAAC. Minor procedures not requiring discontinuation of antithrombotic therapy are permitted (e.g., cardioversion, catheter ablation, cataract surgery);
- The patient has a heart tumor, active infection, signs of physiological tamponade;
- The documented life expectancy of the patient is less than 12 months;
Studijní plán
Jak je studie koncipována?
Detaily designu
Kohorty a intervence
Skupina / kohorta |
Intervence / Léčba |
|---|---|
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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
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Percutaneous left atrial appendage closure using Watchman FLX (Boston Scientific) or Amplatzer Amulet (Abbott) devices
Ostatní jména:
Reduced-dose apixaban 2.5 mg BID for 3 months post-LAAC, followed by complete withdrawal of antithrombotic therapy
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Standard-dose DOAC
Patients receiving long-term standard-dose direct oral anticoagulant (DOAC) therapy per current guidelines
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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
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Composite of major adverse events
Časové okno: 36 months from enrollment
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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)
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36 months from enrollment
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Major bleeding events
Časové okno: 36 months from enrollment
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Incidence of bleeding events classified as BARC type 3 or higher
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36 months from enrollment
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All-cause mortality
Časové okno: 36 months from enrollment
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Incidence of death from any cause
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36 months from enrollment
|
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Ischemic stroke
Časové okno: 36 months from enrollment
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Incidence of ischemic cerebrovascular events confirmed by imaging
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36 months from enrollment
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Systemic embolism
Časové okno: 36 months from enrollment
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Incidence of systemic embolic events excluding stroke
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36 months from enrollment
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Device-related thrombosis
Časové okno: 36 months from enrollment
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Incidence of thrombus formation on the LAAC device detected by imaging (LAAC group only)
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36 months from enrollment
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Peri-device leak
Časové okno: 36 months from enrollment
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Incidence of peri-device leak >3 mm detected by transesophageal echocardiography or cardiac CT (LAAC group only)
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36 months from enrollment
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Spolupracovníci a vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: 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
Publikace a užitečné odkazy
Obecné publikace
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Cévní onemocnění
- Kardiovaskulární choroby
- Patologické procesy
- Srdeční choroba
- Arytmie, srdeční
- Embolie a trombóza
- Patologické stavy, příznaky a symptomy
- Fibrilace síní
- Tromboembolismus
- Krvácení
- Vyšetřovací techniky
- Terapeutika
- Katetrizace
- Srdeční katetrizace
- N (4) -olylcytosin arabinosid
- Apixaban
- BID PROTEIN, LIDSKÝ
- Uzavření přívěsků z levého síní
Další identifikační čísla studie
- 03-03/26
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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