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

NCT ID: NCT05627375

Last Updated: 2025-03-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

1400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-16

Study Completion Date

2028-12-31

Brief Summary

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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

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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).

Conditions

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Venous Thromboembolic Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Full-dose anticoagulant therapy (AC)

Intervention Type DRUG

Anticoagulant (AC) therapy: at the investigator's discretion in accordance with international recommendations for the management of DVT/PE

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

Group Type ACTIVE_COMPARATOR

Full-dose anticoagulant therapy (AC)

Intervention Type DRUG

Anticoagulant (AC) therapy: at the investigator's discretion in accordance with international recommendations for the management of DVT/PE

Antiplatelet therapy (AP)

Intervention Type DRUG

Aspirin (at a daily dose ≤100 mg) or Clopidogrel (at a daily dose ≤75mg)

Interventions

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Full-dose anticoagulant therapy (AC)

Anticoagulant (AC) therapy: at the investigator's discretion in accordance with international recommendations for the management of DVT/PE

Intervention Type DRUG

Antiplatelet therapy (AP)

Aspirin (at a daily dose ≤100 mg) or Clopidogrel (at a daily dose ≤75mg)

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Health, France

OTHER_GOV

Sponsor Role collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Laurent BERTOLETTI, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CHU SAINT-ETIENNE

Locations

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CHU Amiens

Amiens, , France

Site Status RECRUITING

CHU Angers

Angers, , France

Site Status RECRUITING

CHU Besançon - Hôpital Jean Minjoz

Besançon, , France

Site Status RECRUITING

CHRU Brest - Hôpital la Cavale Blanche

Brest, , France

Site Status RECRUITING

Clinique du Parc - Castelnau-le -lez

Castelnau-le-Lez, , France

Site Status RECRUITING

CHU Clermont-Ferrand - Hôpital Gabriel Montpied

Clermont-Ferrand, , France

Site Status RECRUITING

CHU Dijon

Dijon, , France

Site Status RECRUITING

CH le Corbusier - Firminy

Firminy, , France

Site Status RECRUITING

CHU Grenoble - Hôpital la Tronche

Grenoble, , France

Site Status RECRUITING

CH Le Puy - Hôpital Emile Roux

Le Puy-en-Velay, , France

Site Status RECRUITING

CHU Limoges

Limoges, , France

Site Status RECRUITING

HCL - Hôpital Edouard Herriot

Lyon, , France

Site Status RECRUITING

HCL - Lyon Sud

Lyon, , France

Site Status RECRUITING

APHM - Hôpital la Timone

Marseille, , France

Site Status RECRUITING

CH du Forez - Montbrison

Montbrison, , France

Site Status RECRUITING

CHU Montpellier

Montpellier, , France

Site Status RECRUITING

CHU Nancy - Hôpitaux de Brabois

Nancy, , France

Site Status RECRUITING

CHU Nantes - Hôpital Hôtel-Dieu

Nantes, , France

Site Status RECRUITING

CHU de Nice - Hôpital Pasteur

Nice, , France

Site Status RECRUITING

APHP - Hôpital Bicêtre

Paris, , France

Site Status RECRUITING

APHP - Hôpital Européen Georges Pompidou HEGP

Paris, , France

Site Status RECRUITING

APHP - Hôpital Louis Mourier

Paris, , France

Site Status RECRUITING

CHU Rouen

Rouen, , France

Site Status RECRUITING

CHU Saint-Etienne

Saint-Etienne, , France

Site Status RECRUITING

CHU Strasbourg - Nouvel Hôpital Civil

Strasbourg, , France

Site Status RECRUITING

CH Toulon - Hôpital Sainte Musse

Toulon, , France

Site Status RECRUITING

CHU Toulouse - Hôpital de Rangueil

Toulouse, , France

Site Status RECRUITING

CHU Tours

Tours, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Laurent BERTOLETTI, MD PhD

Role: CONTACT

(0)477829121 ext. +33

Carine LABRUYERE

Role: CONTACT

(0)477120469 ext. +33

Other Identifiers

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20PH285

Identifier Type: -

Identifier Source: org_study_id

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