Apixaban for the Prevention of Latent Biological Valve Thrombosis

NCT06184113 | Unknown Phase 4

• 1 other identifier: 8.1-23/77-3; 02/013 AG
• Study Type: interventional
• Target: 166
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first three months. Hypo-attenuated leaflet thickening on cardiac compute tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. The investigators hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reduction of hypo-attenuated leaflet thickening of bioprosthetic valves after aortic valve replacement. Methods: In this prospective, open-label, randomized trial patients without an indication for oral anticoagulation undergoing isolated aortic valve replacement surgery with novel rapid-deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first three months and 100 mg of acetylsalicylic acid thereafter. The control group will have 100 mg of acetylsalicylic acid once a day indefinitely. After the three-month treatment period a contrast enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess possible superiority of the treatment group in the prevention of hypo-attenuated leaflet thickening three months after randomization. Secondary objective is to assess possible noninferiority for safety of apixaban-based strategy when compared to acetylsalicylic acid at three months. Discussion: Antithrombotic therapy after aortic valve replacement surgery is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic event. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses.

Conditions

Aortic Valve Replacement; Antithrombotic Therapy; Bioprosthetic Valve Thrombosis; Rapid Deployment Valves

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with hypo-attenuated leaflet thickening

  Hypo-attenuated leaflet thickening is identified as increased thickness of one or more leaflets of the bioprosthetic valve on contrast-enhanced electrocardiogram gated cardiac computed tomography. Grade 3 on a 4-tier semiquantitative grading scale describes more than 50% and less than 75% of leaflet involvement. Grade 3 or higher of hypo-attenuated leaflet thickening of at least one bioprosthetic valve leaflet will be considered.

  At the end of treatment at 3 months

Secondary Outcomes (1)

• Proportion of patients with bleeding, thromboembolic event, or death

  From enrolment to the end of treatment at 3 months

Other Outcomes (8)

• Rate of hypo-attenuated leaflet thickening

  At the end of treatment at 3 months

• Rate of reduced leaflet mobility

  At the end of treatment at 3 months

• Proportion of patients in each NYHA functional class

  At the end of treatment at 3 months

Study Arms (2)

Intervention Arm

EXPERIMENTAL

Patients randomised to the intervention arm will receive an open-label dose adjusted apixaban twice a day. The treatment will be continued for three months. After the tree-month treatment period apixaban will be stopped and acetylsalicylic acid will be started.

Procedure: Aortic valve replacement surgery; Diagnostic Test: Computed tomography; Diagnostic Test: Echocardiography

Control Arm

ACTIVE COMPARATOR

Patients assigned to the control arm will receive an open-label low dose acetylsalicylic acid indefinitely.

Procedure: Aortic valve replacement surgery; Diagnostic Test: Computed tomography; Diagnostic Test: Echocardiography

Interventions

Aortic valve replacement surgery PROCEDURE

Patients undergoing first-time isolated aortic valve replacement with a rapid deployment biological prosthesis.

Control Arm; Intervention Arm

Computed tomography DIAGNOSTIC_TEST

All the study patients will undergo a computed tomography imaging to assess for hypo-attenuated leaflet thickening and reduced leaflet mobility of the biological prosthesis following the three-month treatment period.

Control Arm; Intervention Arm

Echocardiography DIAGNOSTIC_TEST

All the study patients will undergo a transthoracic echocardiography before hospital discharge and following the three-month treatment period.

Control Arm; Intervention Arm

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Men and women aged 65 or older with aortic valve stenosis undergoing successful isolated first-time aortic valve replacement with a rapid deployment bioprosthetic valve
• Signed informed consent to participate in the research

You may not qualify if:

• Indication for long-term use of anticoagulant therapy
• Indication for dual antiplatelet therapy
• Contraindication to anticoagulation or antiplatelet therapy
• Inability to start the study drug within the planned randomization period
• History of atrial fibrillation
• Known hemorrhagic diathesis
• Presence of other significant heart pathology
• Prior open-heart surgery
• Presence of liver failure or other coagulopathy
• Aortic valve infective endocarditis
• Severe renal failure
• Allergy to iodine contrast

Sponsors & Collaborators

• Clinical Hospital Centre Zagreb: lead

Study Sites (1)

University Hospital Center Zagreb

Zagreb, 10000, Croatia

RECRUITING

Related Publications (1)

• Kopjar T, Gasparovic H, Paar MH, Lovric D, Cerina P, Tokic T, Milicic D. Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial. Trials. 2024 May 16;25(1):324. doi: 10.1186/s13063-024-08175-w.

  PMID: 38755709 DERIVED

MeSH Terms

Interventions

Tomography, X-Ray Computed; Echocardiography

Intervention Hierarchy (Ancestors)

Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Radiographic Image Enhancement; Image Enhancement; Photography; Radiography; Tomography, X-Ray; Tomography; Cardiac Imaging Techniques; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Study Officials

• Tomislav Kopjar, MD, PhD

  Clinical Hospital Centre Zagreb

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tomislav Kopjar, MD, PhD

CONTACT

+385 (1) 2367 520; tomislav.kopjar@kbc-zagreb.hr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 3, 2023
• First Posted: December 28, 2023
• Study Start: December 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: January 3, 2024

Record last verified: 2023-12

Locations

CR (1)