Clinical trial NCT06184113: Apixaban for the Prevention of Latent Biological Valve Thrombosis
Official title: Comparison of Apixaban and Aspirin for the Prevention of Latent Bioprosthetic Valve Thrombosis After Aortic Valve Replacement Surgery: Study Protocol for a Prospective Randomized Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Aortic Valve Replacement
Antithrombotic Therapy
Bioprosthetic Valve Thrombosis
Rapid Deployment Valves
Lead sponsor: Clinical Hospital Centre Zagreb
Sponsor class: OTHER
First posted: 2023-12-28
Enrollment: 166
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Proportion of patients with hypo-attenuated leaflet thickening
timeFrame: At the end of treatment at 3 months
Secondary outcomes:
measure: Proportion of patients with bleeding, thromboembolic event, or death
timeFrame: From enrolment to the end of treatment at 3 months
Other outcomes:
measure: Rate of hypo-attenuated leaflet thickening
timeFrame: At the end of treatment at 3 months
measure: Rate of reduced leaflet mobility
timeFrame: At the end of treatment at 3 months
measure: Proportion of patients in each NYHA functional class
timeFrame: At the end of treatment at 3 months
measure: Rates of bioprosthetic valve deterioration
timeFrame: At the end of treatment at 3 months
measure: Rate of VARC-3 bleeding events
timeFrame: From enrolment to the end of treatment at 3 months
measure: Proportion of patients with myocardial infarction
timeFrame: From enrolment to the end of treatment at 3 months
measure: Proportion of patients with stroke
timeFrame: From enrolment to the end of treatment at 3 months
measure: Proportion of patients that died
timeFrame: From enrolment to the end of treatment at 3 months
Locations:
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb
Study officials:
affiliation: Clinical Hospital Centre Zagreb
name: Tomislav Kopjar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: