Evaluation of Heparin Sodium Versus Placebo for Optimizing Periprocedural Anticoagulation in Patients Undergoing Transseptal Interventions

The primary objective of the STOP CLOT Trial is to determine the optimal timing for initiating **anticoagulation** in patients undergoing interventional procedures that require transseptal puncture, such as Transcatheter Edge-to-Edge Repair (TEER) and Left Atrial Appendage Closure (LAAC). This is clinically relevant as it aims to enhance patient safety and procedural outcomes by minimizing the risk of thromboembolic events and bleeding complications associated with these procedures. The study evaluates the use of **heparin sodium** as the active anticoagulant agent, compared to a placebo, to establish the most effective periprocedural anticoagulation strategy.

The clinical trial focuses on **periprocedural anticoagulant treatment** in patients undergoing Transcatheter Edge-to-Edge Repair (TEER) or transcatheter left atrial appendage closure surgery. The sponsor has not provided information regarding the total number of participants. The study population includes both male and female subjects aged 18 years and older, with no specific vulnerable populations selected. Participants are required to have a planned mitral TEER or left atrial appendage closure procedure. They must express willingness to adhere to the study protocol, particularly concerning follow-up visits, and provide informed consent. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria emphasize the participants' readiness to comply with the study requirements and their eligibility for the specified interventional procedures.

The clinical trial is designed to evaluate the optimal timing for initiating **anticoagulation** in patients undergoing interventional procedures requiring transseptal puncture, such as Transcatheter Edge-to-Edge Repair (TEER) and Left Atrial Appendage Closure (LAAC). This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to run from March 14, 2022, to June 30, 2025, with participant involvement lasting up to 100 days, depending on individual treatment periods.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age above 18 years and planned mitral TEER or LAAC procedure. Following the screening, eligible participants will be randomized to receive either **heparin sodium** or a physiological saline solution as a control. The primary efficacy endpoint is a composite of major adverse cardiac and cerebrovascular events (MACCE) within 30 days post-procedure, intraprocedural new thrombus formation, and new ischemic lesions on brain MRI. Secondary endpoints include moderate or severe bleeding complications and additional MACCE assessments.

Study visits will include follow-up assessments to monitor for adverse events and efficacy outcomes, with brain MRI performed 2 to 5 days post-procedure to detect new ischemic lesions. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any remaining health concerns are addressed. Participants may be terminated early from the study if they experience significant adverse events, withdraw consent, or fail to adhere to the study protocol. The trial aims to provide valuable insights into the management of anticoagulation in patients undergoing these specific interventional procedures.

The clinical trial involves the administration of **Heparin Sodium**, marketed under the name HEPARINUM WZF, 5,000 IU/ml, as a **solution for injection**. This experimental medication is provided by ZAKLADY FARMACEUTYCZNE POLPHARMA S.A. The pharmaceutical form is a solution intended for injection, with a maximum daily dose of 100 IU/kg and a total maximum dose of 1 IU/kg. The treatment period is limited to 100 days. The route of administration is via injection, and the medication is not formulated for pediatric use. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, a **Physiological Saline Solution** is used as a comparator treatment. This solution, known as Injectio Natrii Chlorati Isotonica Polpharma, 9 mg/ml, serves as a placebo in the study. The saline solution is not associated with any active pharmaceutical ingredient and is utilized to maintain the integrity of the study's blinding process. The administration details, including dosage and route, are not specified, as the primary role of this solution is to act as a control within the trial framework.

Efficacy in the clinical trial titled "Strategy To Optimize PeriproCeduraL AnticOagulation in Structural Transseptal Interventions (STOP CLOT Trial)" will be assessed using a composite primary efficacy endpoint. This endpoint includes the occurrence of major adverse cardiac and cerebrovascular events (MACCE), such as death, stroke, transient ischemic attack (TIA), myocardial infarction, or peripheral embolization within 30 days post-procedure. Additionally, the formation of new thrombi in the right or left atrium during the procedure, as evaluated by periprocedural transesophageal echocardiography (TEE), and the appearance of new ischemic lesions with a diameter of ≥4 mm on brain MRI conducted 2 to 5 days after the procedure, will be measured.

The secondary efficacy endpoint focuses on safety and includes moderate or severe bleeding complications (BARC 2-5), including cardiac tamponade requiring intervention during the index hospitalization. It also considers intraprocedural new thrombus formation in the atria assessed by TEE, the occurrence of new ischemic brain lesions on MRI within 2 to 5 days post-procedure, and MACCE within 30 days from the index procedure. These endpoints will be systematically collected and analyzed to determine the efficacy of the anticoagulation strategy in patients undergoing procedures like Transcatheter Edge-to-Edge Repair (TEER) and Left Atrial Appendage Closure (LAAC).