Best Antithrombotic Therapy in patients with acute Venous ThromboEmbolism while taking antiplatelets: the BAT-VTE

The primary objective of this study is to demonstrate the superiority of **full-dose anticoagulant therapy** alone in reducing the risk of clinically relevant bleeding compared to the combination of antiplatelet and full-dose anticoagulant therapy in patients with acute **venous thromboembolism** (VTE) who are receiving antiplatelet therapy for secondary arterial prevention at the time of VTE diagnosis. This is clinically relevant as it aims to optimize antithrombotic therapy by potentially reducing bleeding complications, which are a significant concern in the management of VTE.

Secondary objectives include:

• Demonstrating the superiority of full-dose anticoagulant therapy alone over the combination therapy in terms of net clinical benefit.
• Assessing the safety of full-dose anticoagulant therapy alone compared to combination therapy in terms of clinically relevant bleeding, considering different VTE circumstances such as VTE provoked by a major transient factor, unprovoked VTE, and cancer-associated VTE.
• Evaluating the safety of full-dose anticoagulant therapy alone in terms of major bleeding compared to combination therapy.
• Assessing the efficacy of full-dose anticoagulant therapy alone in terms of vascular events compared to combination therapy.
• Evaluating the efficacy of full-dose anticoagulant therapy alone in terms of VTE sequels compared to combination therapy.

The clinical trial involves participants diagnosed with **acute venous thromboembolism event**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. The participants are not considered a vulnerable population. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants were selected based on specific criteria, including having acute, objectively confirmed symptomatic proximal deep-vein thrombosis or pulmonary embolism, with an indication for full-dose anticoagulant therapy for at least three months. Additionally, participants are required to be on antiplatelet therapy for secondary prevention of atherosclerotic cardiovascular diseases at the time of VTE diagnosis. The trial does not provide specific details regarding the general health status, lifestyle considerations such as diet or physical activity, or habits of the participants.

The clinical trial is designed to evaluate the efficacy of full-dose anticoagulant therapy compared to the combination of antiplatelet and full-dose anticoagulant therapy in patients with **acute venous thromboembolism** (VTE) who are receiving antiplatelet therapy for secondary arterial prevention. This is a randomized, double-blind, controlled trial with an estimated duration of up to 12 months. The trial aims to demonstrate the superiority of full-dose anticoagulant therapy alone in reducing the risk of clinically relevant bleeding events.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as the presence of symptomatic proximal deep-vein thrombosis or pulmonary embolism, and the indication for full-dose anticoagulant therapy for at least three months. Following randomization, participants will attend regular follow-up visits to monitor treatment adherence, assess clinical outcomes, and record any adverse events. The end-of-study visit will evaluate the primary endpoint of clinically relevant bleeding, defined as a composite of major and clinically relevant non-major bleeding events, as well as secondary endpoints including net clinical benefit and vascular events.

The expected length of participant involvement is up to 12 months, with the possibility of early termination if significant adverse events occur or if the participant withdraws consent. The trial will adhere to rigorous ethical standards and regulatory requirements to ensure the safety and well-being of all participants throughout the study period.

The clinical trial involves the administration of **INNOHEP** 10,000 UI anti-Xa/0.5 ml, a **solution for injection** in a pre-filled syringe. The active substance is **tinzaparin sodium**, a polymer-based anticoagulant. The medication is administered via **subcutaneous injection** at a maximum daily dose of 175 IU/kg, with a treatment period not exceeding 10 days. Participant compliance is monitored through regular assessments of injection technique and adherence to dosing schedules.

**COUMADINE** 2 mg, a **tablet** containing **warfarin sodium**, is used as a comparator treatment. This chemical-based anticoagulant is administered orally, with a maximum daily dose of 3 units. The treatment period extends up to 12 weeks. Compliance is monitored through pill counts and regular blood tests to ensure therapeutic levels are maintained.

**CALCIPARINE SOUS CUTANEE** 20,000 UI/0.8 ml, a **solution for injection**, contains **heparin calcium**. This polymer-based anticoagulant is administered via **intravenous use** at a maximum daily dose of 500 IU/kg, with a treatment duration of up to 10 days. Compliance is ensured through monitoring of infusion rates and regular blood coagulation tests.

**HEPARINE CHOAY** 5,000 UI/1 ml, a **solution for injection**, contains **heparin sodium**. This chemical-based anticoagulant is administered intravenously, with a maximum daily dose of 480 IU. The treatment period is limited to 10 days. Compliance is monitored through infusion logs and coagulation parameter assessments.

**Xarelto** 15 mg, a **film-coated tablet**, contains **rivaroxaban**, a chemical-based anticoagulant. It is administered orally, with a maximum daily dose of 30 mg, over a treatment period of 12 weeks. Compliance is monitored through pill counts and periodic blood tests to assess anticoagulation levels.

**Eliquis** 5 mg, a **film-coated tablet**, contains **apixaban**, another chemical-based anticoagulant. It is administered orally, with a maximum daily dose of 20 mg, over a 12-week period. Compliance is ensured through regular pill counts and blood tests to monitor therapeutic levels.

**SINTROM** 4 mg, a **tablet**, contains **acenocoumarol**, a chemical-based anticoagulant. It is administered orally, with a maximum daily dose of 3 units, over a 12-week period. Compliance is monitored through pill counts and regular blood tests to ensure appropriate anticoagulation.

**RESITUNE** 100 mg, a **gastro-resistant tablet**, contains **acetylsalicylic acid**. It is administered orally, with a maximum daily dose of 100 mg, over a 12-week period. Compliance is monitored through pill counts and periodic assessments of gastrointestinal tolerance.

**LOVENOX** 10,000 UI (100 mg)/1 ml, a **solution for injection** in a pre-filled syringe, contains **enoxaparin sodium**. This polymer-based anticoagulant is administered via **subcutaneous injection** at a maximum daily dose of 200 IU/kg, with a treatment period not exceeding 10 days. Compliance is monitored through regular assessments of injection technique and adherence to dosing schedules.

**Arixtra** 7.5 mg/0.6 ml, a **solution for injection** in a pre-filled syringe, contains **fondaparinux sodium**, a chemical-based anticoagulant. It is administered via **subcutaneous use** at a maximum daily dose of 7.5 mg, with a treatment period of up to 10 days. Compliance is monitored through regular assessments of injection technique and adherence to dosing schedules.

**KARDEGIC** 75 mg, an **oral solution**, contains **D,L-lysine acetylsalicylate**, a chemical-based anticoagulant. It is administered orally, with a maximum daily dose of 75 mg, over a 12-week period. Compliance is monitored through regular assessments of solution preparation and adherence to dosing schedules.

**FRAGMINE** 7,500 U.l. anti Xa/0.75 ml, a **solution for injection** in a pre-filled syringe, contains **dalteparin sodium**. This polymer-based anticoagulant is administered via **subcutaneous use** at a maximum daily dose of 200 IU/kg, with a treatment period not exceeding 10 days. Compliance is monitored through regular assessments of injection technique and adherence to dosing schedules.

**Plavix** 75 mg, a **film-coated tablet**, contains **clopidogrel**, a chemical-based antiplatelet agent. It is administered orally, with a maximum daily dose of 75 mg, over a 12-week period. Compliance is monitored through pill counts and periodic assessments of platelet function.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the occurrence of clinically relevant bleeding, which is defined as a composite of major bleeding events and clinically relevant non-major bleeding events, as per the International Society on Thrombosis and Haemostasis (ISTH) criteria. This will be evaluated at the end of the full-dose treatment period or up to 12 months.

Secondary endpoints include a net clinical benefit, which is a composite measure of clinically relevant bleeding, recurrent venous thromboembolism, and major adverse ischemic cardiovascular and cerebrovascular events. Additional secondary endpoints are the individual components of clinically relevant bleeding, major bleeding, and vascular events, which include recurrent venous thromboembolism and major adverse cardiovascular and cerebrovascular events. The trial will also assess VTE sequels, defined as the composite of post-thrombotic syndrome and/or post-pulmonary embolism syndrome.

The efficacy parameters will be collected and analyzed at the end of the full-dose treatment period or up to 12 months, ensuring a comprehensive evaluation of the treatment's impact on patients with acute **Venous ThromboEmbolism** (VTE) who are receiving antiplatelet therapy for secondary arterial prevention. The trial aims to demonstrate the superiority of full-dose anticoagulant therapy alone compared to the combination of antiplatelet and full-dose anticoagulant therapy in reducing the risk of clinically relevant bleeding.