Valve Disease, HeartPhase 3SAFE-HEARTNCT07434661
Apixaban VS Warfarin in AF Pts First Three Months After Repair or BIO AVR MVR
A Phase 3 study testing Apixaban and Warfarin in people with Valve Disease, Heart and Atrial Fibrillation (AF), run by Meshalkin Research Institute of Pathology of Circulation at 1 site in Russia.
Trial summary
SAFE-HEART is a single-centre, randomized controlled trial comparing the safety and efficiency of Apixaban versus Warfarin in the early period (3 months) after repair or bioprosthetics of the mitral and aortic valve cardiac surgery in patients with atrial fibrillation requiring oral anticoagulation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Valve Disease, Heart, Atrial Fibrillation (AF), Valve Replacement Surgery
- What is being tested?
- Apixaban and Warfarin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteRussia
- Study dates
- Feb 2026to Jan 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
- Age ≥18 years at the time of enrolment
- Open heart aortic or mitral valve repair or biological valve replacement in the last 10 days
- Atrial fibrillation requiring anticoagulation (including pre-existing or post-operative atrial fibrillation),
- Informed consent from either the patient or a substitute decision-maker.
Who cannot join
- Mechanical valve replacement
- Antiphospholipid syndrome (triple positive)
- Severe renal failure (Cockcroft-Gault equation; creatinine clearance <15 ml/min)
- Known significant liver disease (Child-Pugh classification B and C)
- Left ventricular thrombus
- Ongoing bleeding, hemorrhagic disorders, or bleeding diathesis
Show all 9Show fewer
- Known contraindication for any DOAC or VKA
- Women who are pregnant, breastfeeding, or of childbearing potential
- Follow-up not possible
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Maria Agarkova contact
Russia1 site
"E.Meshalkin National Medical Research Center" of the Ministry of Health of the Russian Federation
Novosibirsk
About this study
Official title: Safety and Efficacy of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in the First Three Months After Mitral or Aortic Biological Valve Replacement or Repair
SAFE-HEART is a single-centre, randomized controlled trial comparing the safety and efficiency of Apixaban versus Warfarin in the early period (3 months) after repair or bioprosthetics of the mitral and aortic valve cardiac surgery in patients with atrial fibrillation requiring oral anticoagulation.
Read the detailed description
Oral anticoagulation with vitamin K antagonists (VKAs) is currently recommended for 3 months following surgical reconstruction or bioprosthetic replacement of the mitral and aortic valves, regardless of rhythm status.
Despite their effectiveness, the use of warfarin is limited by its narrow therapeutic index, which requires frequent international normalized ratio (INR) measurements to ensure adequate anticoagulation levels. This key limitation leads to failure to maintain target INR levels and treatment discontinuation. Additionally, in the first 3 months after heart surgery, the duration of the therapeutic period is short, even with careful monitoring by experienced physicians.
Over the past decade, direct oral anticoagulants (DOACs)-factor Xa or thrombin inhibitors-have gained widespread use in anticoagulant therapy. It has been demonstrated that DOAC treatment in patients with atrial fibrillation reduces the risk of stroke or systemic embolism and carries a similar risk of major bleeding compared to VKAs during long-term follow-up in patients with atrial fibrillation. Moreover, they offer rapid onset of action, fixed dosing, no need for laboratory monitoring, and minimal interactions with food and other medications. In the postoperative period, DOAC use may also shorten hospital stays and reduce costs.
However, the safety of DOACs in the first months after surgical valve correction (reconstruction/bioprosthetic replacement of the mitral and aortic valves) remains uncertain, which is reflected in the recommendation classes for anticoagulant therapy following these procedures.
The purpose of this study is to establish whether Apixaban is as safe and effective as Warfarin in the first 3 months after reconstruction or bioprosthetics of the mitral and aortic valvescardiac surgery in patients with atrial fibrillation requiring oral anticoagulation.
- Conditions
- Valve Disease, Heart, Atrial Fibrillation (AF), Valve Replacement Surgery, Aortic Valve Surgery, Mitral Valve Annuloplasty, Mitral Valve Repair
- Keywords
- anticoagulation, bioprosthetics, atrial fibrillation, mitral valve repair, aortic valve repair, Apixaban, Warfarin
- Medical subject headings
- Heart Valve Diseases, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Patients in the intervention group will receive Apixaban at doses recommended for the indication, adjusted for their renal function is required.
WarfarinDrug
Patients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range.
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Active comparator | Patients in the intervention group will receive Apixaban at doses recommended for the indication, adjusted for their renal function is required. Receives: Drug: Apixaban |
| Warfarin | Placebo comparator | Patients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range. Receives: Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Bleeding
Major bleeding defined as bleeding that results in death and/or symptomatic bleeding in a critical area or organ, bleeding into a surgical site requiring reoperation, bleeding leading to hospitalization (including presentation to an acute care facility without overnight stay) and/or bleeding that causes a drop in the hemoglobin level of 20g/L or more or that which requires the transfusion of ≥2 units of packed red blood cells or whole blood (as defined by the International Society of Thrombosis and Hemostasis)
Measured: 3 months
Death and/or thromboembolic complications
Stroke Myocardial infarction Intracardiac thrombosis Systemic embolism Deep vein thrombosis Pulmonary embolism
Measured: 3 months
Secondary outcomes (4)
Minor Bleeding
Measured: 3 months
Quality of Life - EQ-5D-5L
EQ-5D is a standardised instrument developed by the EuroQol Group to provide a simple, generic measure of HRQoL for clinical and economic appraisal The descriptive system measures five dimensions of health: MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN / DISCOMFORT and ANXIETY / DEPRESSION. Each dimension has five response levels: no problems, slight problems, moderate problems, severe problems, unable to/extreme problems. The respondent is asked to indicate his/her health state by checking the box next to the most appropriate response level for them in each of the five dimensions. Responses are coded as single-digit numbers expressing the severity level selected in each dimention.
The EQ VAS records the respondent's overall current health on a vertical visual analogue scale (0-100), where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The EQ VAS provides a quantitative measure of the patient's perception of their overall health.
Measured: 3 months
Patient Satisfaction with Anticoagulant treatment
This indicator will be assessed using a questionnaire (Perception of Anticoagulant Treatment Questionnaire (PACT-Q)). The Perception of Anticoagulant Treatment Questionnaire (PACT-Q) is a validated, two-part, 20-item patient-reported tool that measures expectations (PACT-Q1) before treatment and convenience/satisfaction (PACT-Q2) during treatment. All theitems of PACT-Q1 and PACT-Q2 parts are to be answeredon a 5-point Likert scale.
Measured: 3 months
Pleural or pericardial effusion requiring drainage
Incidence of pericarditis/pleuritis requiring drainage in both groups
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2026
- Study startFeb 2026 (estimated)
- Primary completionJan 2028 (estimated)
- Study completionJan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Valve Disease, HeartStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Meshalkin Research Institute of Pathology of Circulation
- Sponsor type
- Research network
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07434661
- Sponsor's protocol ID
- A568096267900
- Acronym
- SAFE-HEART
- Status last verified
- Jan 2026
- First submitted
- 21 Jan 2026
- Last updated
- 25 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in the First Three Months After Mitral or Aortic Biological Valve Replacement or Repair
- ClinicalTrials.gov ID
- NCT07434661
- Acronym / sponsor ID
- SAFE-HEART / A568096267900
- Conditions
- Valve Disease, Heart, Atrial Fibrillation (AF), Valve Replacement Surgery, Aortic Valve Surgery, Mitral Valve Annuloplasty, Mitral Valve Repair
- Keywords
- anticoagulation, bioprosthetics, atrial fibrillation, mitral valve repair, aortic valve repair, Apixaban, Warfarin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Meshalkin Research Institute of Pathology of CirculationResearch network
- Study start
- Feb 2026 (estimated)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jan 2029 (estimated)
- First posted
- 25 Feb 2026 (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.
SAFE-HEART is a single-centre, randomized controlled trial comparing the safety and efficiency of Apixaban versus Warfarin in the early period (3 months) after repair or bioprosthetics of the mitral and aortic valve cardiac surgery in patients with atrial fibrillation requiring oral anticoagulation.
Detailed description
Oral anticoagulation with vitamin K antagonists (VKAs) is currently recommended for 3 months following surgical reconstruction or bioprosthetic replacement of the mitral and aortic valves, regardless of rhythm status.
Despite their effectiveness, the use of warfarin is limited by its narrow therapeutic index, which requires frequent international normalized ratio (INR) measurements to ensure adequate anticoagulation levels. This key limitation leads to failure to maintain target INR levels and treatment discontinuation. Additionally, in the first 3 months after heart surgery, the duration of the therapeutic period is short, even with careful monitoring by experienced physicians.
Over the past decade, direct oral anticoagulants (DOACs)-factor Xa or thrombin inhibitors-have gained widespread use in anticoagulant therapy. It has been demonstrated that DOAC treatment in patients with atrial fibrillation reduces the risk of stroke or systemic embolism and carries a similar risk of major bleeding compared to VKAs during long-term follow-up in patients with atrial fibrillation. Moreover, they offer rapid onset of action, fixed dosing, no need for laboratory monitoring, and minimal interactions with food and other medications. In the postoperative period, DOAC use may also shorten hospital stays and reduce costs.
However, the safety of DOACs in the first months after surgical valve correction (reconstruction/bioprosthetic replacement of the mitral and aortic valves) remains uncertain, which is reflected in the recommendation classes for anticoagulant therapy following these procedures.
The purpose of this study is to establish whether Apixaban is as safe and effective as Warfarin in the first 3 months after reconstruction or bioprosthetics of the mitral and aortic valvescardiac surgery in patients with atrial fibrillation requiring oral anticoagulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Active comparator | Drug: ApixabanPatients in the intervention group will receive Apixaban at doses recommended for the indication, adjusted for their renal function is required. |
| Warfarin | Placebo comparator | Drug: WarfarinPatients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥18 years at the time of enrolment
- Open heart aortic or mitral valve repair or biological valve replacement in the last 10 days
- Atrial fibrillation requiring anticoagulation (including pre-existing or post-operative atrial fibrillation),
- Informed consent from either the patient or a substitute decision-maker.
Key exclusion criteria (9 listed)
- Mechanical valve replacement
- Antiphospholipid syndrome (triple positive)
- Severe renal failure (Cockcroft-Gault equation; creatinine clearance <15 ml/min)
- Known significant liver disease (Child-Pugh classification B and C)
- Left ventricular thrombus
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 |
|---|---|---|
| ApixabanPatients in the intervention group will receive Apixaban at doses recommended for the indication, adjusted for their renal function is required. | Drug | Apixaban |
| WarfarinPatients in the control group will receive VKA once daily; the individual dose will be titrated to achieve a guideline-recommended INR range. | Drug | Warfarin |
Primary outcome
Major Bleeding
Time frame: 3 months
Major bleeding defined as bleeding that results in death and/or symptomatic bleeding in a critical area or organ, bleeding into a surgical site requiring reoperation, bleeding leading to hospitalization (including presentation to an acute care facility without overnight stay) and/or bleeding that causes a drop in the hemoglobin level of 20g/L or more or that which requires the transfusion of ≥2 units of packed red blood cells or whole blood (as defined by the International Society of Thrombosis and Hemostasis)
Death and/or thromboembolic complications
Time frame: 3 months
Stroke Myocardial infarction Intracardiac thrombosis Systemic embolism Deep vein thrombosis Pulmonary embolism
4 secondary outcomes
Minor Bleeding
Time frame: 3 months
Quality of Life - EQ-5D-5L
Time frame: 3 months
Patient Satisfaction with Anticoagulant treatment
Time frame: 3 months
Pleural or pericardial effusion requiring drainage
Time frame: 3 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 25 Feb 2026.
- 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.
Maria Agarkova contact
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 and Warfarin in people with Valve Disease, Heart and Atrial Fibrillation (AF), run by Meshalkin Research Institute of Pathology of Circulation at 1 site in Russia.
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 4 inclusion and 9 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 25 Feb 2026. 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 Russia. 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. Some participants in this study may receive a placebo. 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 Alexander Afanasyev (+7 (383) 347-60-99, a_afanasyev@meshalkin.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Bleeding (time frame: 3 months). The study lists 2 primary outcomes in all. 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 25 Feb 2026.