Clinical trial NCT05627375: Best Antithrombotic Therapy in Patients With Acute Venous ThromboEmbolism While Taking Antiplatelets
Official title: Best Antithrombotic Therapy in Patients With Acute Venous ThromboEmbolism While Taking Antiplatelets
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Venous Thromboembolic Disease
Keywords: deep venous thrombosis
pulmonary embolism
anticoagulant
antiplatelet
Venous Thromboembolism
Direct oral anticoagulants
major adverse ischemic cardiovascular and cerebrovascular event
secondary prevention
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2022-11-25
Enrollment: 1400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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

Primary outcomes:
measure: Clinically relevant bleeding
timeFrame: end of the full-dose treatment period, up to 12 months
Secondary outcomes:
measure: Net clinical benefit
timeFrame: end of the full-dose AC treatment period, up to 12 months
measure: Clinically relevant non-major bleeding
timeFrame: end of the full-dose treatment period, up to 12 months
measure: Major bleeding events
timeFrame: end of the full-dose treatment period, up to 12 months
measure: recurrent venous thromboembolism
timeFrame: end of the full-dose treatment period, up to 12 months
measure: arterial events
timeFrame: end of the full-dose treatment period, up to 12 months
measure: venous thromboembolism (VTE) sequels
timeFrame: end of the full-dose treatment period, up to 12 months
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: CHU Besançon - Hôpital Jean Minjoz
city: Brest
country: France
facility: CHRU Brest - Hôpital la Cavale Blanche
city: Castelnau-le-Lez
country: France
facility: Clinique du Parc - Castelnau-le -lez
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand - Hôpital Gabriel Montpied
city: Dijon
country: France
facility: CHU Dijon
city: Firminy
country: France
facility: CH le Corbusier - Firminy
city: Grenoble
country: France
facility: CHU Grenoble - Hôpital la Tronche
city: Le Puy-en-Velay
country: France
facility: CH Le Puy - Hôpital Emile Roux
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: HCL - Hôpital Edouard Herriot
city: Lyon
country: France
facility: HCL - Lyon Sud
city: Marseille
country: France
facility: APHM - Hôpital la Timone
city: Montbrison
country: France
facility: CH du Forez - Montbrison
city: Montpellier
country: France
facility: CHU Montpellier
city: Nancy
country: France
facility: CHU Nancy - Hôpitaux de Brabois
city: Nantes
country: France
facility: CHU Nantes - Hôpital Hôtel-Dieu
city: Nice
country: France
facility: CHU de Nice - Hôpital Pasteur
city: Paris
country: France
facility: APHP - Hôpital Bicêtre
city: Paris
country: France
facility: APHP - Hôpital Européen Georges Pompidou HEGP
city: Paris
country: France
facility: APHP - Hôpital Louis Mourier
city: Rouen
country: France
facility: CHU Rouen
city: Saint-Étienne
country: France
facility: CHU Saint-Etienne
city: Strasbourg
country: France
facility: CHU Strasbourg - Nouvel Hôpital Civil
city: Toulon
country: France
facility: CH Toulon - Hôpital Sainte Musse
city: Toulouse
country: France
facility: CHU Toulouse - Hôpital de Rangueil
city: Tours
country: France
facility: CHU Tours
Study officials:
affiliation: CHU SAINT-ETIENNE
name: Laurent BERTOLETTI, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: