Aortic Valve DiseasePhase 3DIAMONDNCT05687448
DIrect Oral Anticoagulation and Bioprothesis Aortic Valve
A Phase 3 study testing Apixaban 5 MG Oral Tablet and Aspirin 75 to 100mg once a day in people with Aortic Valve Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
DIAMOND study is a national, multicentre, randomized, parallel-group, open label study in patients (aged ≥18 years) with aortic bioprosthesis (excluding TAVI) at least 7 days after cardiac surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aortic Valve Disease
- What is being tested?
- Apixaban 5 MG Oral Tablet and Aspirin 75 to 100mg once a day
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,500 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2025to Mar 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥18 years of age
- Prior implantation of a surgical bioprosthesis in the aortic position at least 7 days and before hospital discharge (excluding TAVI)
- Participants currently not requiring chronic anticoagulation for another reason (atrial fibrillation, pulmonary embolism or any other condition)
- Patients affiliated to social security
- Patient able to give free, informed and written consent
Who cannot join
- Any cardiac surgery less than 7 days prior to enrollment or more than 1 month
- Mechanical valve in any position or combined valve surgery (mitral or tricuspid).
- Any major bleeding in the three months (90 days) prior to enrollment.
- Active bleeding or high risk of bleeding after cardiac surgery (i.e. hemopericardium) or lesion or condition considered as a significant risk factor for major bleeding according to investigator
- Atrial fibrillation requiring chronic anticoagulation
- Need to be on dual antiplatelet therapy (aspirin >100 mg daily and a P2Y12 inhibitor, i.e. clopidogrel, ticagrelor, prasugrel) or requiring chronic anticoagulation whatever the treatment (oral or injection).
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- Known hypersensitivity or other contraindications to apixaban (hepatic disease associated with coagulopathy and clinically relevant bleeding risk).
- Creatinine clearance <40 mL/min (Cockcroft) or patients requiring apixaban dose reduction.
- Known hypersensitivity or other contraindications to aspirin (Hypersensitivity to aspirin or any of the excipients, history of asthma induced by the administration of salicylates, ongoing peptic ulcer, constitutional or acquired hemorrhagic disease including gastrointestinal bleeding, history of hemorrhagic stroke and thrombocytopenia, pregnancy after 24 weeks of gestation, risk of bleeding, severe renal failure, severe hepatic impairment, uncontrolled severe heart failure
- Known hypersensitivity or other contraindications to heparin or low molecular weight heparin (history of heparin-induced thrombocytopenia, hypersensitivity to any of the excipients…)
- Ischemic stroke within 1 month or intracranial hemorrhage
- Active endocarditis at the time of screening for enrollment.
- Women of childbearing potential without efficient contraception, pregnant or breastfeeding women.
- Concomitant combined strong P-gp and CYP3A4 inducers or inhibitors.
- History of non-compliance
- Participation in another interventional study
- Active cancer or life expectancy less than 1 year
- Persons deprived of their liberty by judicial or administrative decision
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: DIrect Oral Anticoagulant for Antithrombotic Management Of Aortic Bioprothesis Valve implaNted Patients for Valvular Heart Disease Study
DIAMOND study is a national, multicentre, randomized, parallel-group, open label study in patients (aged ≥18 years) with aortic bioprosthesis (excluding TAVI) at least 7 days after cardiac surgery.
Experimental group:
Read more
Patients treated with apixaban 5 mg twice daily (BID)
Active Comparator group:
Aspirin 75 to 100mg once a day
The primary objective is to demonstrate that antithrombotic treatment with apixaban is superior to aspirin in patients with recent surgical bioprosthetic aortic valve replacement for the primary composite efficacy endpoint of death from any cause, myocardial infarction, stroke, systemic embolism, deep vein thrombosis, or pulmonary embolism and valve thrombosis after 105 days of follow-up.
Read the detailed description
Early antithrombotic management of patients who have undergone aortic valve replacement using a bioprosthesis remains a source of medical concern. The optimal antithrombotic strategy early after surgery remains controversial due to lack of high-quality evidence. Some observational studies support the use of vitamin K antagonists (VKAs) compared to aspirin (ASA) to significantly reduce the risk of thromboembolism but suffer from major source of bias inherent to retrospective analyses of observational data. A small, randomized trial found that VKA for 3 months significantly increased major bleeding compared with ASA, without reducing the rate of deaths or thromboembolic events but this study was underpowered for ischemic events. There is therefore a lack of evidence demonstrating the superiority of anticoagulant treatment compared to aspirin early after bioprosthetic aortic valve surgery. Current ESC guidelines recommend that ASA or VKA should be considered for 3 months after surgical implantation of an aortic bioprosthesis. At the opposite, current AHA/ACC guidelines recommend that anticoagulation with VKA to achieve an INR of 2.5 is reasonable for at least 3 months and for as long as 6 months for patients at low risk of bleeding (IIa, level B). However, anticoagulation by VKAs is currently underused and guideline recommendations are not followed by most clinicians as VKAs have major drawbacks: narrow therapeutic window, variable dose-response in individuals, interaction with several foods and drugs.
Despite their superiority to reduce bleeding in patients with non-valvular atrial fibrillation compared to VKAs, direct oral anticoagulants (DOACs) including apixaban have not been well evaluated in the first 3 months after surgical bioprosthetic valve implantation. A small, randomized trial found that edoxaban was non-inferior to warfarin for preventing thromboembolism and the occurrence of major bleeding in the first 3 months after aortic or mitral surgical bioprosthetic valve implantation. DOAC(s) are effective in patients with atrial fibrillation and bioprosthetic valve implanted after 3 months.
Finally, there is an unmet clinical need for an alternative to ASA or VKAs, such as an anti-Xa DOAC like apixaban, as anticoagulation in patients in the first 3 months after surgical bioprosthetic valve implantation.
The purpose of this study is to compare the efficacy of apixaban and aspirin on ischemic endpoints during the first 3 months after aortic surgical bioprosthetic valve implantation excluding TAVI.
- Conditions
- Aortic Valve Disease
- Being tested
- Apixaban 5 MG Oral Tablet, Aspirin 75 to 100mg once a day
- Keywords
- Anticoagulant, Aortic valve, Apixaban, Aspirin, Stroke, Hemorrhage
- Medical subject headings
- Aortic Valve Disease, Stroke, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apixaban 5 MG Oral TabletDrug
Also called Experimental Group
Patients treated with apixaban 5 mg twice daily (BID)
Aspirin 75 to 100mg once a dayDrug
Also called Active Comparator
Patients treated with Aspirin 75 to 100mg once a day
| Study group | Role | What they receive |
|---|---|---|
| Experimental Group | Experimental | Patients treated with apixaban 5 mg twice daily (BID) Receives: Drug: Apixaban 5 MG Oral Tablet |
| Active Comparator group: | Active comparator | Patients treated with Aspirin 75 to 100mg once a day Receives: Drug: Aspirin 75 to 100mg once a day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Adverse Clinical Events (MACE)
The primary endpoint is a composite efficacy endpoint including death from any cause, myocardial infarction, stroke, systemic embolism, deep vein thrombosis, or pulmonary embolism and valve thrombosis.
Measured: Up to 3.5 months
Secondary outcomes (12)
Bleeding
ISTH major and non-major clinically relevant bleeding
Measured: Up to 3.5 months
Death
Including cardiovascular and non cardiovascular death
Measured: Up to 3.5 months
Myocardial infarction
Measured: Up to 3.5 months
Stroke
Measured: Up to 3.5 months
Systemic embolism
Measured: Up to 3.5 months
Deep vein thrombosis or pulmonary embolism
Measured: Up to 3.5 months
Valve thrombosis
Measured: Up to 3.5 months
Bleeding
According to ISTH major and non-major clinically relevant bleeding, BARC and TIMI 6, BARC and TIMI Classifications
Measured: Up to 3.5 months
Echographic parameter of aortic valve
Variation of mean aortic gradient (mm/Hg)
Measured: Up to 3.5 months
Assessment of coagulation
Measured by thrombin generation in a subgroup population (n=216)
Measured: Up to 3.5 months
To evaluate platelet activation (sP-selectin) in a subgroup population (n = 216)
Measured: Up to 3.5 months
To build a population PK/PD in the experimental group
Measuring the apixaban concentration (anti-Xa activity expressed in ng/mL) (apixaban, n = 108)
Measured: Up to 3.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2023
- Study startSep 2025 (estimated)
- Primary completionSep 2025 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic Valve DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This study is a national, multicentre, randomized, parallel-group, open label study in patients (aged ≥18 years) with aortic bioprosthesis at least 7 days after cardiac surgery. Experimental group: Patients treated with apixaban 5 mg twice daily (BID) Active Comparator group: Aspirin 75 to 100mg once a day
- Masking
- None (open label)
- Enrolment
- 1,500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Guillaume DILLINGER, Professor, Principal investigator, Assistance Publique Hôpitaux Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05687448
- Sponsor's protocol ID
- 2024-516643-64-00
- Acronym
- DIAMOND
- Status last verified
- Jun 2025
- First submitted
- 26 Sep 2022
- Last updated
- 12 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DIrect Oral Anticoagulant for Antithrombotic Management Of Aortic Bioprothesis Valve implaNted Patients for Valvular Heart Disease Study
- ClinicalTrials.gov ID
- NCT05687448
- Acronym / sponsor ID
- DIAMOND / 2024-516643-64-00
- Conditions
- Aortic Valve Disease
- Keywords
- Anticoagulant, Aortic valve, Apixaban, Aspirin, Stroke, Hemorrhage
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 1,500 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2025 (estimated)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Mar 2029 (estimated)
- First posted
- 18 Jan 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.
DIAMOND study is a national, multicentre, randomized, parallel-group, open label study in patients (aged ≥18 years) with aortic bioprosthesis (excluding TAVI) at least 7 days after cardiac surgery.
Experimental group:
Patients treated with apixaban 5 mg twice daily (BID)
Active Comparator group:
Aspirin 75 to 100mg once a day
The primary objective is to demonstrate that antithrombotic treatment with apixaban is superior to aspirin in patients with recent surgical bioprosthetic aortic valve replacement for the primary composite efficacy endpoint of death from any cause, myocardial infarction, stroke, systemic embolism, deep vein thrombosis, or pulmonary embolism and valve thrombosis after 105 days of follow-up.
Detailed description
Early antithrombotic management of patients who have undergone aortic valve replacement using a bioprosthesis remains a source of medical concern. The optimal antithrombotic strategy early after surgery remains controversial due to lack of high-quality evidence. Some observational studies support the use of vitamin K antagonists (VKAs) compared to aspirin (ASA) to significantly reduce the risk of thromboembolism but suffer from major source of bias inherent to retrospective analyses of observational data. A small, randomized trial found that VKA for 3 months significantly increased major bleeding compared with ASA, without reducing the rate of deaths or thromboembolic events but this study was underpowered for ischemic events. There is therefore a lack of evidence demonstrating the superiority of anticoagulant treatment compared to aspirin early after bioprosthetic aortic valve surgery. Current ESC guidelines recommend that ASA or VKA should be considered for 3 months after surgical implantation of an aortic bioprosthesis. At the opposite, current AHA/ACC guidelines recommend that anticoagulation with VKA to achieve an INR of 2.5 is reasonable for at least 3 months and for as long as 6 months for patients at low risk of bleeding (IIa, level B). However, anticoagulation by VKAs is currently underused and guideline recommendations are not followed by most clinicians as VKAs have major drawbacks: narrow therapeutic window, variable dose-response in individuals, interaction with several foods and drugs.
Despite their superiority to reduce bleeding in patients with non-valvular atrial fibrillation compared to VKAs, direct oral anticoagulants (DOACs) including apixaban have not been well evaluated in the first 3 months after surgical bioprosthetic valve implantation. A small, randomized trial found that edoxaban was non-inferior to warfarin for preventing thromboembolism and the occurrence of major bleeding in the first 3 months after aortic or mitral surgical bioprosthetic valve implantation. DOAC(s) are effective in patients with atrial fibrillation and bioprosthetic valve implanted after 3 months.
Finally, there is an unmet clinical need for an alternative to ASA or VKAs, such as an anti-Xa DOAC like apixaban, as anticoagulation in patients in the first 3 months after surgical bioprosthetic valve implantation.
The purpose of this study is to compare the efficacy of apixaban and aspirin on ischemic endpoints during the first 3 months after aortic surgical bioprosthetic valve implantation excluding TAVI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This study is a national, multicentre, randomized, parallel-group, open label study in patients (aged ≥18 years) with aortic bioprosthesis at least 7 days after cardiac surgery. Experimental group: Patients treated with apixaban 5 mg twice daily (BID) Active Comparator group: Aspirin 75 to 100mg once a day
| Arm | Type | Receives |
|---|---|---|
| Experimental Group | Experimental | Drug: Apixaban 5 MG Oral TabletPatients treated with apixaban 5 mg twice daily (BID) |
| Active Comparator group: | Active comparator | Drug: Aspirin 75 to 100mg once a dayPatients treated with Aspirin 75 to 100mg once a day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female ≥18 years of age
- Prior implantation of a surgical bioprosthesis in the aortic position at least 7 days and before hospital discharge (excluding TAVI)
- Participants currently not requiring chronic anticoagulation for another reason (atrial fibrillation, pulmonary embolism or any other condition)
- Patients affiliated to social security
- Patient able to give free, informed and written consent
Key exclusion criteria (18 listed)
- Any cardiac surgery less than 7 days prior to enrollment or more than 1 month
- Mechanical valve in any position or combined valve surgery (mitral or tricuspid).
- Any major bleeding in the three months (90 days) prior to enrollment.
- Active bleeding or high risk of bleeding after cardiac surgery (i.e. hemopericardium) or lesion or condition considered as a significant risk factor for major bleeding according to investigator
- Atrial fibrillation requiring chronic anticoagulation
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 |
|---|---|---|
| Apixaban 5 MG Oral TabletAlso: Experimental GroupPatients treated with apixaban 5 mg twice daily (BID) | Drug | Experimental Group |
| Aspirin 75 to 100mg once a dayAlso: Active ComparatorPatients treated with Aspirin 75 to 100mg once a day | Drug | Active Comparator group: |
Primary outcome
Major Adverse Clinical Events (MACE)
Time frame: Up to 3.5 months
The primary endpoint is a composite efficacy endpoint including death from any cause, myocardial infarction, stroke, systemic embolism, deep vein thrombosis, or pulmonary embolism and valve thrombosis.
12 secondary outcomes
Bleeding
Time frame: Up to 3.5 months
Death
Time frame: Up to 3.5 months
Myocardial infarction
Time frame: Up to 3.5 months
Stroke
Time frame: Up to 3.5 months
Systemic embolism
Time frame: Up to 3.5 months
Deep vein thrombosis or pulmonary embolism
Time frame: Up to 3.5 months
Valve thrombosis
Time frame: Up to 3.5 months
Bleeding
Time frame: Up to 3.5 months
Echographic parameter of aortic valve
Time frame: Up to 3.5 months
Assessment of coagulation
Time frame: Up to 3.5 months
To evaluate platelet activation (sP-selectin) in a subgroup population (n = 216)
Time frame: Up to 3.5 months
To build a population PK/PD in the experimental group
Time frame: Up to 3.5 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2025.
- Individual participant dataSharing planned: No
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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.
Jean-Guillaume DILLINGER, Professor principal investigator
Assistance Publique Hôpitaux Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban 5 MG Oral Tablet and Aspirin 75 to 100mg once a day in people with Aortic Valve Disease, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 5 inclusion and 18 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: opening soon, as of the sponsor's last update on 12 Jun 2025. 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 France. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean-Guillaume DILLINGER, Professor (+33 1 49 95 86 74, jean-guillaume.dillinger@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Adverse Clinical Events (MACE) (time frame: Up to 3.5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jun 2025.