Best Antithrombotic Therapy in Patients With Acute Venous ThromboEmbolism While Taking Antiplatelets
- Conditions
- Venous Thromboembolic Disease
- Interventions
- Drug: Full-dose anticoagulant therapy (AC)Drug: Antiplatelet therapy (AP)
- Registration Number
- NCT05627375
- Brief 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.
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1400
Not provided
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description strategy of full-dose anticoagulant therapy alone (AC) Full-dose anticoagulant therapy (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. strategy of combined full-dose anticoagulant and antiplatelet therapies (AC+AP) Full-dose anticoagulant therapy (AC) 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 strategy of combined full-dose anticoagulant and antiplatelet therapies (AC+AP) Antiplatelet therapy (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
- Primary Outcome Measures
Name Time Method Clinically relevant bleeding end of the full-dose treatment period, up to 12 months Clinically relevant bleeding is composite of major bleeding events and clinically relevant non-major bleeding events).
- Secondary Outcome Measures
Name Time Method Clinically relevant non-major bleeding end of the full-dose treatment period, up to 12 months Net clinical benefit end of the full-dose AC treatment period, up to 12 months Net clinical benefit is defined by the composite of clinically relevant bleeding, recurrent venous thromboembolism, and major adverse ischemic cardiovascular and cerebrovascular events
recurrent venous thromboembolism end of the full-dose treatment period, up to 12 months proximal deep venous thromboembolism and/or pulmonary embolism symptomatic or incidental, and including fatal-PE
Major bleeding events end of the full-dose treatment period, up to 12 months arterial events end of the full-dose treatment period, up to 12 months 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),
venous thromboembolism (VTE) sequels end of the full-dose treatment period, up to 12 months 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
Trial Locations
- Locations (28)
HCL - Hôpital Edouard Herriot
🇫🇷Lyon, France
CHU de Nice - Hôpital Pasteur
🇫🇷Nice, France
CHU Besançon - Hôpital Jean Minjoz
🇫🇷Besançon, France
CHU Dijon
🇫🇷Dijon, France
CHRU Brest - Hôpital la Cavale Blanche
🇫🇷Brest, France
APHM - Hôpital la Timone
🇫🇷Marseille, France
APHP - Hôpital Bicêtre
🇫🇷Paris, France
CHU Angers
🇫🇷Angers, France
CHU Saint-Etienne
🇫🇷Saint-Étienne, France
CHU Montpellier
🇫🇷Montpellier, France
CHU Nancy - Hôpitaux de Brabois
🇫🇷Nancy, France
CHU Amiens
🇫🇷Amiens, France
CH le Corbusier - Firminy
🇫🇷Firminy, France
HCL - Lyon Sud
🇫🇷Lyon, France
APHP - Hôpital Européen Georges Pompidou HEGP
🇫🇷Paris, France
APHP - Hôpital Louis Mourier
🇫🇷Paris, France
CHU Nantes - Hôpital Hôtel-Dieu
🇫🇷Nantes, France
CHU Rouen
🇫🇷Rouen, France
CHU Strasbourg - Nouvel Hôpital Civil
🇫🇷Strasbourg, France
CHU Toulouse - Hôpital de Rangueil
🇫🇷Toulouse, France
CHU Tours
🇫🇷Tours, France
CHU Clermont-Ferrand - Hôpital Gabriel Montpied
🇫🇷Clermont-Ferrand, France
CHU Grenoble - Hôpital la Tronche
🇫🇷Grenoble, France
CH Le Puy - Hôpital Emile Roux
🇫🇷Le Puy-en-Velay, France
CHU Limoges
🇫🇷Limoges, France
CH du Forez - Montbrison
🇫🇷Montbrison, France
Clinique du Parc - Castelnau-le -lez
🇫🇷Castelnau-le-Lez, France
CH Toulon - Hôpital Sainte Musse
🇫🇷Toulon, France