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

• ClinicalTrials.gov Identifier: NCT05627375
• Recruitment Status: Recruiting
• First Posted: November 25, 2022
• Last Update Posted: March 6, 2024
• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborator: Ministry of Health, France
• Information provided by (Responsible Party): Centre Hospitalier Universitaire de Saint Etienne

Tracking Information

• First Submitted Date: November 16, 2022
• First Posted Date: November 25, 2022
• Last Update Posted Date: March 6, 2024
• Actual Study Start Date: August 16, 2023
• Estimated Primary Completion Date: December 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 13, 2023)

Clinically relevant bleeding [ Time Frame: 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).

Original Primary Outcome Measures (submitted: November 16, 2022)

Clinically relevant bleeding [ Time Frame: end of the full-dose treatment period or 12 months ]

Clinically relevant bleeding is composite of major bleeding events and clinically relevant non-major bleeding events).

Current Secondary Outcome Measures (submitted: April 7, 2023)

• Net clinical benefit [ Time Frame: 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
• Clinically relevant non-major bleeding [ Time Frame: end of the full-dose treatment period, up to 12 months ]
• Major bleeding events [ Time Frame: end of the full-dose treatment period, up to 12 months ]
• recurrent venous thromboembolism [ Time Frame: 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
• arterial events [ Time Frame: 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 [ Time Frame: 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

Original Secondary Outcome Measures (submitted: November 16, 2022)

• Net clinical benefit [ Time Frame: end of the full-dose treatment period or 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
• Clinically relevant non-major bleeding [ Time Frame: end of the full-dose treatment period or 12 months ]
• Major bleeding events [ Time Frame: end of the full-dose treatment period or 12 months ]
• recurrent venous thromboembolism [ Time Frame: end of the full-dose treatment period or 12 months ]
  proximal deep venous thromboembolism and/or pulmonary embolism symptomatic or incidental, and including fatal-PE
• arterial events [ Time Frame: end of the full-dose treatment period or 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 [ Time Frame: end of the full-dose treatment period or 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)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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).

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Venous Thromboembolic Disease

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

Study Arms

• 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.

  Intervention: Drug: Full-dose anticoagulant therapy (AC)
• 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

  Interventions:

  • Drug: Full-dose anticoagulant therapy (AC)
  • Drug: Antiplatelet therapy (AP)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 16, 2022): 1400
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2028
• Estimated Primary Completion Date: December 2027 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Laurent BERTOLETTI, MD PhD; (0)477829121 ext +33; laurent.bertoletti@chu-st-etienne.fr

Contact: Carine LABRUYERE; (0)477120469 ext +33; carine.labruyere@chu-st-etienne.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT05627375
• Other Study ID Numbers: 20PH285
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
• Original Responsible Party: Same as current
• Current Study Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Original Study Sponsor: Same as current
• Collaborators: Ministry of Health, France

Investigators

• Principal Investigator: Laurent BERTOLETTI, MD PhD; CHU Saint-Etienne

• PRS Account: Centre Hospitalier Universitaire de Saint Etienne
• Verification Date: March 2024