Aortic Valve ReplacementPhase 4NCT06184113
Apixaban for the Prevention of Latent Biological Valve Thrombosis
A Phase 4 study testing Aortic valve replacement surgery, Computed tomography and Echocardiography in people with Aortic Valve Replacement and Antithrombotic Therapy, run by Clinical Hospital Centre Zagreb at 1 site in Croatia.
Trial 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. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Aortic Valve Replacement, Antithrombotic Therapy, Bioprosthetic Valve Thrombosis
- What is being tested?
- Aortic valve replacement surgery, Computed tomography and Echocardiography
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 166 participants
- Where
- 1 siteCroatia
- Study dates
- Dec 2023to Dec 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Croatia1 site, 1 recruiting
- Recruiting
University Hospital Center Zagreb
Zagreb, 10000
Tomislav Kopjar, MD PhD
About this study
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
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
- Being tested
- Aortic valve replacement surgery, Computed tomography, Echocardiography
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aortic valve replacement surgeryProcedure or surgery
Patients undergoing first-time isolated aortic valve replacement with a rapid deployment biological prosthesis.
Computed tomographyDiagnostic 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.
EchocardiographyDiagnostic test
All the study patients will undergo a transthoracic echocardiography before hospital discharge and following the three-month treatment period.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Aortic valve replacement surgery; Diagnostic Test: Computed tomography; Diagnostic Test: Echocardiography |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At the end of treatment at 3 months
Secondary outcomes (1)
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.
Measured: From enrolment to the end of treatment at 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2023
- Study startDec 2023 (estimated)
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve ReplacementStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 166 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Hospital Centre Zagreb
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tomislav Kopjar, Clinical Hospital Centre Zagreb
- Investigators
- Tomislav Kopjar, MD, PhD, Principal investigator, Clinical Hospital Centre Zagreb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06184113
- Sponsor's protocol ID
- 8.1-23/77-3; 02/013 AG
- Status last verified
- Dec 2023
- First submitted
- 3 Dec 2023
- Last updated
- 3 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38755709
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06184113
- Acronym / sponsor ID
- 8.1-23/77-3; 02/013 AG
- Conditions
- Aortic Valve Replacement, Antithrombotic Therapy, Bioprosthetic Valve Thrombosis, Rapid Deployment Valves
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 166 participants (estimated)
- Lead sponsor
- Clinical Hospital Centre ZagrebUniversity, hospital or other
- Study start
- Dec 2023 (estimated)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 28 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Arm | Experimental | Procedure: Aortic valve replacement surgery, Diagnostic Test: Computed tomography, Diagnostic Test: EchocardiographyPatients 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. |
| Control Arm | Active comparator | Procedure: Aortic valve replacement surgery, Diagnostic Test: Computed tomography, Diagnostic Test: EchocardiographyPatients assigned to the control arm will receive an open-label low dose acetylsalicylic acid indefinitely. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aortic valve replacement surgeryPatients undergoing first-time isolated aortic valve replacement with a rapid deployment biological prosthesis. | Procedure or surgery | Control Arm, Intervention Arm |
| Computed tomographyAll 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. | Diagnostic test | Control Arm, Intervention Arm |
| EchocardiographyAll the study patients will undergo a transthoracic echocardiography before hospital discharge and following the three-month treatment period. | Diagnostic test | Control Arm, Intervention Arm |
Primary outcome
Proportion of patients with hypo-attenuated leaflet thickening
Time frame: At the end of treatment at 3 months
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.
1 secondary outcome
Proportion of patients with bleeding, thromboembolic event, or death
Time frame: From enrolment to the end of treatment at 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2024.
- Derived from this study: PubMed 38755709Kopjar 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.
Related trials for Aortic Valve Replacement
Recruiting
Trial of the F2 Filter and Delivery System for Embolic Protection During TAVR
Aortic Stenosis Treated With TAVI, Aortic Diseases
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
RecruitingObservational study
Valve Performance of the SAPIEN 3 Ultra RESILIA Valve: A Prospective Registry With Central Echocardiography Analysis.
Aortic Valve Stenosis, Transcatheter Aortic Valve Replacement
Active, not recruiting
Medtronic Evolut Transcatheter Aortic Valve Replacement in Low Risk Patients
Aortic Valve Stenosis
Recruiting
SYMmetric Valve fraME Expansion To Reduce hYpoattenuated Leaflet Thickening After Balloon-expandable TAVI: the SYMMETRY Trial
Aortic Valve Stenosis and/or Insufficiency, Hypoattenuated Leaflet Thickening
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tomislav Kopjar, MD, PhD principal investigator
Clinical Hospital Centre Zagreb
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Aortic valve replacement surgery, Computed tomography and Echocardiography in people with Aortic Valve Replacement and Antithrombotic Therapy, run by Clinical Hospital Centre Zagreb at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tomislav Kopjar, MD, PhD (+385 (1) 2367 520, tomislav.kopjar@kbc-zagreb.hr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with hypo-attenuated leaflet thickening (time frame: At the end of treatment at 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06184113, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2024.