Optimal PeriproCeduraL AnticOagulation in Structural Transseptal Interventions (STOP CLOT)

Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions

The transcatheter edge to edge mitral valve repair (TEER) and left atrial appendage closure (LAAC) are the interventional cardiology procedures that require periprocedural anticoagulation with unfractionated heparin (UFH). The UFH is administered either before or immediately after transseptal puncture, at the discretion of the operator

The aim of the study is to establish the optimal timing of initiation of periprocedural anticoagulation in patients undergoing structural heart interventions requiring transseptal puncture (TEER and LAAC), Patients who undergo TEER implantation or LAAC procedure will be randomized to two groups:

1. Early UFH administration. The iv. bolus of UFH (100Units/kg) will be given after obtained femoral vein access and at least 5 minutes prior to the start of the TSP.
2. Late UFH administration. The iv. bolus of UFH (100Units/kg) will be given immediately after TSP, defined as the introduction of transseptal sheath into the left atrium.

Study Overview

• Status: Enrolling by invitation
• Conditions: Atrial Fibrillation; Mitral Regurgitation; Anticoagulation
• Intervention / Treatment: Other: early anticoagulation; Other: late anticoagulation

• Study Type: Interventional
• Enrollment (Estimated): 410
• Phase: Phase 4

Contacts and Locations

Study Locations

• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne Gdański Uniwersytet Medyczny
  • Katowice, Poland
    • Górnośląskie Centrum Medyczne im. Leszka Gieca Śląskiego Uniwersytetu Medycznego
  • Lublin, Poland
    • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
  • Poznan, Poland, 60-355
    • Uniwersytecki Szpital Kliniczny W Poznaniu
  • Warsaw, Poland
    • Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years on the day of signing the informed consent form.
2. Planned treatment of mitral regurgitation using the TEER technique (MitraClip or Pascal system) or planned left atrial appendage closure (Watchman system or Amplatzer system).
3. The participant expresses willingness to comply with the study protocol, in particular the protocol-defined follow-up visits.
4. The participant is willing to provide written informed consent to participate in the study.

Exclusion Criteria:

1. Pregnant or lactating women, and women of childbearing potential who do not agree to use at least two methods of contraception (oral contraceptives, barrier methods, approved contraceptive implants, injectable depot contraceptives, intrauterine devices, or tubal ligation). This does not apply to women who are postmenopausal (≥ 1 year from last menses) for ≥ 2 years AND, if < 55 years old, have a negative pregnancy test within 24 hours prior to randomization, or have undergone surgical sterilization.
2. Any diagnosed, acquired, or congenital bleeding or coagulation disorders (e.g., diagnosed thrombophilia, bleeding diatheses).
3. INR > 1.5 within 24 hours prior to the procedure in patients chronically treated with vitamin K antagonists.
4. Last dose of non-vitamin K antagonist oral anticoagulant (NOAC) < 48 hours before the procedure, in patients receiving NOAC therapy.
5. Last dose of low-molecular-weight heparin (LMWH) < 12 hours before the procedure, in patients receiving LMWH therapy.
6. Presence of contraindications to brain magnetic resonance imaging (e.g., claustrophobia, metallic implants/prostheses).

7. Presence of cardiac implantable electronic devices (implantable cardioverter-defibrillator [ICD], permanent pacemaker, or cardiac resynchronization therapy [CRT] system) in the following situations:

   • Epicardial leads
   • Left disconnected leads or non-functional or damaged devices
   • Devices implanted within abdominal wall
   • Pacemaker dependent patients (Lack of escape rhythm > 30 bpm).
   • Patients in whom less than 6 weeks have elapsed since system implantation or replacement.
   • Patients in whom pre-MRI system interrogation reveals abnormalities in system function or cardiac arrhythmias that, in the opinion of the supervising electrophysiology team, could compromise MRI safety.
   • Patients whose device battery on the day of the MRI examination has less than 20% voltage between nominal and ERI, or the projected device longevity is less than 1 year.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early UFH administration; The iv. bolus of UFH (100Units/kg) will be given after obtained femoral vein access and at least 5 minutes prior to the start of the TSP.	Other: early anticoagulation; Anticoagulation prior to transseptal puncture
Active Comparator: Late UFH administration; The iv. bolus of UFH (100Units/kg) will be given immediately after TSP, defined as the introduction of transseptal sheath into the left atrium.	Other: late anticoagulation; Anticoagulation after transseptal puncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. MACCE 2. Intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transsesophageal echocardiography 3. Occurrence of new ischemic lesions with diameter ≥4 mm in brain MR performed 2-5 days after procedure	Major adverse cardiac and cerebrovascular events (MACCE) will include: death (all-cause and cardiovascular), stroke, TIA, non-fatal myocardial infarction or peripheral embolization, within 30 days from the index procedure.	Within 30 days from the index procedure

Secondary Outcome Measures

Outcome Measure	Time Frame
Moderate and severe bleeding complications (BARC 2-5) including cardiac tamponade requiring intervention during the index hospitalization	during the hospitalization related to the index procedure but up to 30 days from randomization
Occurrence of new ischemic brain lesion in the MR examination performed within 2-5 days post index procedure.	within 2-5 days post index procedure
Intraprocedural fresh thrombus formation in the right or left atrium as assessed with periprocedural transsesophageal echocardiography	during index procedure
Major adverse cardiac and cerebrovascular events death (all-cause and cardiovascular), stroke, TIA, non-fatal myocardial infarction or peripheral embolization, within 30 days from the index procedure.	within 30 days from index procedure

Collaborators and Investigators

• Sponsor: National Institute of Cardiology, Warsaw, Poland
• Collaborators: Medical Research Agency, Poland; Soft Communication, Poland
• Investigators: Principal Investigator: Jerzy Pręgowski, MD, PhD, National Institute of Cardiology

Publications and helpful links

General Publications

• Pregowski J, Pracon R, Mioduszewska A, Skowronski J, Sondergaard L, Mintz GS, Capodanno D, Kim SW, De Baker O, Wacinski P, Wojakowski W, Rdzanek A, Grygier M, Chmielecki M, Franco LN, Stoklosa P, Firek B, Marczak M, Milosz B, Chmielak Z, Demkow M, Witkowski A. Strategy to optimize PeriproCeduraL AnticOagulation in structural transseptal interventions: Design and rationale of the STOP CLOT trial. Am Heart J. 2024 May;271:68-75. doi: 10.1016/j.ahj.2024.02.015. Epub 2024 Feb 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 14, 2022
• First Submitted That Met QC Criteria: March 28, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 14, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Valve Diseases; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Mitral Valve Insufficiency
• Other Study ID Numbers: ABM/2020/1/00002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: to be defined
• IPD Sharing Time Frame: IPD sharing will be considered after study completion and publication of the results.
• IPD Sharing Access Criteria: to be defined
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No