Best Antithrombotic Therapy in Patients With Acute Venous ThromboEmbolism While Taking Antiplatelets (BAT-VTE)

Venous thromboembolism (VTE) and atherosclerotic cardiovascular disease share common risk factors and frequently coexist in the same patients.

Their management requires use of antithrombotic agents: anticoagulant therapy (AC) for secondary prevention of VTE recurrence, antiplatelet (AP) for secondary prevention of major adverse ischemic cardiovascular and cerebrovascular event (MACCE) in patients with atherosclerotic cardiovascular disease (coronary artery disease, atherosclerotic cerebrovascular disease, lower extremity peripheral arterial disease).

Side effects of antithrombotic drugs are the 1st cause of emergency admission and hospitalization for an adverse drug reaction (mainly bleeding), and the combination of AC with AP strongly increases this risk.

Study Overview

• Status: Recruiting
• Conditions: Venous Thromboembolic Disease
• Intervention / Treatment: Drug: Antiplatelet therapy (AP); Drug: Full-dose anticoagulant therapy (AC)

Detailed Description

Up to one third of VTE patients receive concomitant AP therapy, with conflicting results on patient outcomes. Concomitant therapy (AC+AP) has been associated with a higher risk of bleeding (up to 3-fold) when aspirin was associated with vitamin-K antagonist (VKA) in a multicenter cohort study, or with direct oral anticoagulants (DOACs) for acute VTE in a post-hoc subgroup analysis. Conversely, patients with acute VTE in whom clinicians decided to maintain AC+AP were found to have an increased risk of MACCE without any higher risk of bleeding, in a multicenter registry. However, in most cases, the type (aspirin or another) and indication (primary versus secondary prevention) of AP was unknown, as was the duration of the combination AC+AP, and therefore these observational results may be confounded. Therefore, there is persistent equipoise regarding the benefit/risk of combining an antiplatelet therapy with anticoagulation in patients undergoing treatment for VTE, when there is a prior history of atherosclerotic cardiovascular disease. This may explain why clinical practice varies widely.

Considering the conflicting data about the risk of bleeding in patients on AP therapy for secondary prevention, who need to start full-dose anticoagulant therapy for acute VTE, a randomized trial comparing the two strategies, in patients with acute VTE and with history of stable atherosclerotic cardiovascular disease is needed and justified.

The investigators hypothesize that a strategy based on the prescription of a full-dose AC therapy alone will decrease the risk of bleeding, when compared to the the strategy of combined AP and full-dose AC therapies, and that this strategy will translate in a positive net clinical benefit (a composite of clinically relevant bleeding, recurrent venous thromboembolism, and major adverse ischemic cardiovascular and cerebrovascular events).

• Study Type: Interventional
• Enrollment (Estimated): 1400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Laurent BERTOLETTI, MD PhD; Phone Number: +33 (0)477829121; Email: laurent.bertoletti@chu-st-etienne.fr
• Study Contact Backup: Name: Carine LABRUYERE; Phone Number: +33 (0)477120469; Email: carine.labruyere@chu-st-etienne.fr

Study Locations

• France
  • Amiens, France
    • Recruiting
    • CHU Amiens
    • Principal Investigator: Marie-Antoinette SEVESTRE-PIETRI, MD PhD
  • Angers, France
    • Recruiting
    • CHU Angers
    • Principal Investigator: Pierre-Marie ROY, MD PhD
  • Besançon, France
    • Recruiting
    • CHU Besancon - Hôpital Jean Minjoz
    • Principal Investigator: Nicolas MENNEVEAU, MD PhD
  • Brest, France
    • Recruiting
    • CHRU Brest - Hôpital la Cavale Blanche
    • Principal Investigator: Francis COUTURAUD, MD PhD
  • Castelnau-le-Lez, France
    • Recruiting
    • Clinique du Parc - Castelnau-le -lez
    • Principal Investigator: Dominique BRISOT, MD
  • Clermont-Ferrand, France
    • Recruiting
    • CHU Clermont-Ferrand - Hôpital Gabriel Montpied
    • Principal Investigator: Jeannot SCHMIDT, MD PhD
  • Dijon, France
    • Recruiting
    • CHU Dijon
    • Principal Investigator: Nicolas Falvo, MD
  • Firminy, France
    • Recruiting
    • CH le Corbusier - Firminy
    • Principal Investigator: François BALLEREAU, MD
  • Grenoble, France
    • Recruiting
    • CHU Grenoble - Hôpital la Tronche
    • Principal Investigator: Gilles PERNOD, MD PhD
  • Le Puy-en-Velay, France
    • Recruiting
    • CH Le Puy - Hôpital Emile Roux
    • Principal Investigator: Mathieu VALADIER, MD
  • Limoges, France
    • Recruiting
    • CHU Limoges
    • Principal Investigator: Philippe LACROIX, MD PhD
  • Lyon, France
    • Recruiting
    • HCL - Hôpital Edouard Herriot
    • Principal Investigator: Hélène DESMURS, MD
  • Lyon, France
    • Recruiting
    • HCL - Lyon Sud
    • Principal Investigator: Claire GRANGE, MD
  • Marseille, France
    • Recruiting
    • APHM - Hôpital la Timone
    • Principal Investigator: Gabrielle SARLON, MD PhD
  • Montbrison, France
    • Recruiting
    • CH du Forez - Montbrison
    • Principal Investigator: Mikaël MARTINEZ, MD
  • Montpellier, France
    • Recruiting
    • CHU Montpellier
    • Principal Investigator: Isabelle QUERE, MD PhD
  • Nancy, France
    • Recruiting
    • CHU Nancy - Hôpitaux de Brabois
    • Principal Investigator: Stéphane ZUILY, MD PhD
  • Nantes, France
    • Recruiting
    • CHU Nantes - Hôpital Hotel-Dieu
    • Principal Investigator: Jérôme CONNAULT, MD
  • Nice, France
    • Recruiting
    • CHU de Nice - Hopital Pasteur
    • Principal Investigator: Emile FERRARI, MD PhD
  • Paris, France
    • Recruiting
    • APHP - Hôpital Bicêtre
    • Principal Investigator: David MONTANI, MD PhD
  • Paris, France
    • Recruiting
    • APHP - Hôpital Européen Georges Pompidou HEGP
    • Principal Investigator: Olivier SANCHEZ, MD PhD
  • Paris, France
    • Recruiting
    • APHP - Hôpital Louis Mourier
    • Principal Investigator: Isabelle MAHE, MD PhD
  • Rouen, France
    • Recruiting
    • CHU Rouen
    • Principal Investigator: Ygal BENHAMOU, MD
  • Saint-Etienne, France
    • Recruiting
    • CHU Saint-Etienne
    • Principal Investigator: Laurent Bertoletti, MD PhD
  • Strasbourg, France
    • Recruiting
    • CHU Strasbourg - Nouvel Hopital Civil
    • Principal Investigator: Dominique STEPHAN, MD PhD
  • Toulon, France
    • Recruiting
    • CH Toulon - Hôpital Sainte Musse
    • Principal Investigator: Antoine ELIAS, MD
  • Toulouse, France
    • Recruiting
    • CHU Toulouse - Hopital de Rangueil
    • Principal Investigator: Alessandra BURA-RIVIERE, MD PhD
  • Tours, France
    • Recruiting
    • CHU Tours
    • Principal Investigator: Denis ANGOULVANT, MD PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria

• Signed informed consent
• Patients with acute objectively confirmed symptomatic proximal deep-vein thrombosis (DVT) or pulmonary embolism (PE) (with or without deep-vein thrombosis). Proximal deep-vein thrombosis is defined as thrombosis involving at least the popliteal vein or a more proximal vein of the lower limb.
• Indication of full-dose anticoagulant therapy for at least 3 months.
• Prescription of antiplatelet therapy for secondary prevention of atherosclerotic cardiovascular diseases, at the time of VTE diagnosis
• Life expectancy more than 3 months
• Social security affiliation

Exclusion Criteria:

• Unable to give informed consent
• Active bleeding or a high risk of bleeding contraindicating anticoagulant treatment; a systolic blood pressure of more than 180 mm Hg or a diastolic blood pressure of more than 110 mm Hg
• Anticoagulation for more than 5 days prior to randomization
• Active pregnancy or expected pregnancy or no effective contraception
• Isolated distal deep vein thrombosis
• Antiplatelet therapy prescribed for primary prevention of cardiovascular disease
• Indication to maintain a dual-antiplatelet therapy.
• Triple positive antiphospholipid syndrome, with arterial thrombosis
• Major cardiovascular and cerebrovascular event in the past 12 months for acute coronary syndrome, and in the past 6 months for cerebrovascular diseases and peripheral arterial diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: strategy of full-dose anticoagulant therapy alone (AC); The experimental group receiving full-dose anticoagulant therapy alone (AC). Anticoagulant (AC) therapy :at the investigator's discretion in accordance with international recommendations for the management of DVT/PE Antiplatelet therapy will be stopped.	Drug: Full-dose anticoagulant therapy (AC); Anticoagulant (AC) therapy: at the investigator's discretion in accordance with international recommendations for the management of DVT/PE
Active Comparator: strategy of combined full-dose anticoagulant and antiplatelet therapies (AC+AP); The control group receiving the standard of care: Antiplatelet therapy will be combined to full-dose anticoagulant therapy. Anticoagulant (AC) therapy :at the investigator's discretion in accordance with international recommendations for the management of DVT/PE Antiplatelet (AP) therapy : Aspirin or Clopidogrel	Drug: Antiplatelet therapy (AP); Aspirin (at a daily dose ≤100 mg) or Clopidogrel (at a daily dose ≤75mg); Drug: Full-dose anticoagulant therapy (AC); Anticoagulant (AC) therapy: at the investigator's discretion in accordance with international recommendations for the management of DVT/PE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically relevant bleeding	Clinically relevant bleeding is composite of major bleeding events and clinically relevant non-major bleeding events).	end of the full-dose treatment period, up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically relevant non-major bleeding		end of the full-dose treatment period, up to 12 months
Major bleeding events		end of the full-dose treatment period, up to 12 months
recurrent venous thromboembolism	proximal deep venous thromboembolism and/or pulmonary embolism symptomatic or incidental, and including fatal-PE	end of the full-dose treatment period, up to 12 months
arterial events	major adverse cardiovascular and cerebrovascular events (nonfatal ischemic stroke, nonfatal myocardial infarction, acute lower limb ischemia, lower limb amputation or revascularization for vascular causes, cardiovascular deaths),	end of the full-dose treatment period, up to 12 months
Net clinical benefit	Net clinical benefit is defined by the composite of clinically relevant bleeding, recurrent venous thromboembolism, and major adverse ischemic cardiovascular and cerebrovascular events	end of the full-dose AC treatment period, up to 12 months
venous thromboembolism (VTE) sequels	post-thrombotic syndrome (defined as a Villalta score up to 4) and post-PE syndrome (defined as the combination of a persistant dyspnea with a NYHA (New York Heart Association) scale more than I with residual vascular obstruction on lung scan	end of the full-dose treatment period, up to 12 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Laurent BERTOLETTI, MD PhD, Centre Hospitalier Universitaire de Saint Etienne

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 16, 2022
• First Submitted That Met QC Criteria: November 16, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: anticoagulant; Venous Thromboembolism; pulmonary embolism; secondary prevention; deep venous thrombosis; antiplatelet; Direct oral anticoagulants; major adverse ischemic cardiovascular and cerebrovascular event
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thromboembolism; Thrombosis; Pulmonary Embolism; Venous Thrombosis; Venous Thromboembolism; Anticoagulants
• Other Study ID Numbers: 20PH285

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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