A Phase 4 interventional study of Aortic valve replacement surgery and Computed tomography in Aortic Valve Replacement, Antithrombotic Therapy and Bioprosthetic Valve Thrombosis, sponsored by Clinical Hospital Centre Zagreb. Recruiting at 1 site in Croatia. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2024-01-03.
Sponsored by Clinical Hospital Centre Zagreb · Phase 4, Interventional, and Treatment
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.
1,506 studies on the registry are indexed under Thrombosis; 238 are open to participants now.
This study's planned enrollment of 166 is above the median of 106 across 849 interventional studies indexed under Thrombosis.
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Exclusion Criteria:
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
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
Patients undergoing first-time isolated aortic valve replacement with a rapid deployment biological prosthesis.
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.
All the study patients will undergo a transthoracic echocardiography before hospital discharge and following the three-month treatment period.
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.
Time frame: At the end of treatment at 3 months
Proportion of patients with bleeding, thromboembolic event, or death
The safety composite outcome will be comprised of all types of VARC-3 bleeding events, thromboembolic events (myocardial infarction and stroke), and death from any cause.
Time frame: From enrolment to the end of treatment at 3 months
Rate of 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 which will be considered significant. Grade 3 or higher will be considered significant.
Time frame: At the end of treatment at 3 months
Rate of reduced leaflet mobility
Leaflet restriction caused by hypo-attenuated leaflet thickening can be described as reduced leaflet mobility. Using computed tomography, reduced leaflet motion will be assessed on short-axis reformatted images during systole and 4D volume rendering images. The extent can be described per leaflet, using a 4-tier grading scale in systole: (1) not present, (2) \< 50% restriction in leaflet excursion, (3) ≥50% restriction in leaflet excursion and (4) immobile leaflet. Grade 3 or higher will be considered significant.
Time frame: At the end of treatment at 3 months
Proportion of patients in each NYHA functional class
New York Heart Association functional classification of heart failure. Class I, no limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation or shortness of breath. Class II, slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, shortness of breath or chest pain. Class III, marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, shortness of breath or chest pain. Class IV, symptoms of heart failure at rest. Any physical activity causes further discomfort.
Time frame: At the end of treatment at 3 months
Rates of bioprosthetic valve deterioration
Stage 1 is described with morphological valve deterioration without significant hemodynamic changes. Stage 2 is characterized with moderate hemodynamic valve deterioration with an increase in mean transvalvular gradient ≥10 mmHg, and Stage 3 with severe hemodynamic valve deterioration with an increase in mean transvalvular gradient ≥20 mmHg.
Time frame: At the end of treatment at 3 months
Rate of VARC-3 bleeding events
A descriptive classification scheme for VARC-3 bleeding, like the Bleeding Academic Research Consortium classification has been proposed. It includes 4-type bleeding scale: Type 1 (minor), Type 2 (major), Type 3 (life-threatening), and Type 4 (leading to death) bleeding.
Time frame: From enrolment to the end of treatment at 3 months
Proportion of patients with myocardial infarction
Myocardial infarction with elevated biomarkers cTn values with at least symptoms of acute ischaemia, new ischaemic ECG changes, new pathologic Q-waves, imaging evidence of a new loss of viable myocardium or new wall motion abnormality, identification of a coronary thrombus by angiography or autopsy.
Time frame: From enrolment to the end of treatment at 3 months
Proportion of patients with stroke
All stroke (ischaemic stroke, haemorrhagic stroke, or any stroke not otherwise specified) with signs and symptoms and with pathology or neuroimaging evidence of central nervous system infarction, or absence of other apparent causes.
Time frame: From enrolment to the end of treatment at 3 months
Proportion of patients that died
All cause mortality.
Time frame: From enrolment to the end of treatment at 3 months
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Clinical Hospital Centre Zagreb