Best Antithrombotic Therapy in Patients With Acute Venous ThromboEmbolism While Taking Antiplatelets

Venous Thromboembolic Disease Clinical Trial

— BAT-VTE  

Official title:

Best Antithrombotic Therapy in Patients With Acute Venous ThromboEmbolism While Taking Antiplatelets

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05627375
• Other study ID #: 20PH285
• Status: Recruiting
• Phase: Phase 3
• Start date: August 16, 2023
• Est. completion date: December 2028

Study information

• Verified date: March 2024
• Source: Centre Hospitalier Universitaire de Saint Etienne
• Contact: Laurent BERTOLETTI, MD PhD
• Phone: (0)477829121
• Email: laurent.bertoletti[@]chu-st-etienne.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1400
• Est. completion date: December 2028
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolic Disease
• Venous Thromboembolism

Intervention

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
• Antiplatelet therapy (AP)
Aspirin (at a daily dose =100 mg) or Clopidogrel (at a daily dose =75mg)

Locations

Country	Name	City	State
France	CHU Amiens	Amiens
France	CHU Angers	Angers
France	CHU Besançon - Hôpital Jean Minjoz	Besançon
France	CHRU Brest - Hôpital la Cavale Blanche	Brest
France	Clinique du Parc - Castelnau-le -lez	Castelnau-le-Lez
France	CHU Clermont-Ferrand - Hôpital Gabriel Montpied	Clermont-Ferrand
France	CHU Dijon	Dijon
France	CH le Corbusier - Firminy	Firminy
France	CHU Grenoble - Hôpital la Tronche	Grenoble
France	CH Le Puy - Hôpital Emile Roux	Le Puy-en-Velay
France	CHU Limoges	Limoges
France	HCL - Hôpital Edouard Herriot	Lyon
France	HCL - Lyon Sud	Lyon
France	APHM - Hôpital la Timone	Marseille
France	CH du Forez - Montbrison	Montbrison
France	CHU Montpellier	Montpellier
France	CHU Nancy - Hôpitaux de Brabois	Nancy
France	CHU Nantes - Hôpital Hôtel-Dieu	Nantes
France	CHU de Nice - Hôpital Pasteur	Nice
France	APHP - Hôpital Bicêtre	Paris
France	APHP - Hôpital Européen Georges Pompidou HEGP	Paris
France	APHP - Hôpital Louis Mourier	Paris
France	CHU Rouen	Rouen
France	CHU Saint-Etienne	Saint-Étienne
France	CHU Strasbourg - Nouvel Hôpital Civil	Strasbourg
France	CH Toulon - Hôpital Sainte Musse	Toulon
France	CHU Toulouse - Hôpital de Rangueil	Toulouse
France	CHU Tours	Tours

Sponsors (2)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Saint Etienne	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Clinically relevant non-major bleeding		end of the full-dose treatment period, up to 12 months
Secondary	Major bleeding events		end of the full-dose treatment period, up to 12 months
Secondary	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
Secondary	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
Secondary	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