Skip to main content
OpenTrials
Completed

NCT Number: NCT05035277

AntiCoagulation Versus AcetylSalicylic Acid After Transcatheter Aortic Valve Implantation

ACASA-TAVI is a pragmatic randomized controlled trial assessing the value of anticoagulation therapy versus the standard antiplatelet therapy after transcatheter aortic valve implantation in patients with aortic stenosis. The trial will assess the efficacy of direct oral anticoagulation (DOAC) therapy compared to the standard single antiplatelet therapy to prevent degeneration of the valve and its safety in co-primary endpoints with blinded endpoint adjudication. The effect of DOAC therapy on hard clinical outcomes will be assessed during long-term follow-up.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Aortic Stenosis Aortic Valve Disease Aortic Valve Stenosis Cardiovascular Diseases Heart Diseases Heart Valve Diseases Ventricular Outflow Obstruction

Age range

65 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Oslo Univesity Hospital - Ullevål, Oslo, Norway

Loading trial locations.

About this study

Aortic stenosis is a highly prevalent valvular disease and an important cause of morbidity and mortality in the elderly population. Transcatheter aortic valve implantation (TAVI) is an effective intervention in patients with severe aortic stenosis and low surgical risk. The procedure is highly effective, safe, and widely implemented. Current recommendations support transcatheter treatment of younger patients, including patients from 65 years of age with low surgical risk. This practice increases the importance of long-term valve maintenance.

Observational data have suggested that early signs of valve degeneration (i.e. hypo-attenuated leaflet thickening/thrombosis/reduced leaflet motion) are associated with an increased risk of embolic events. This is an increasing problem with emerging indications in younger populations. Because both ischemic and bleeding complications after TAVI can be life-threatening, it is important to establish the optimal anti-thrombotic treatment regime. Use of oral anticoagulation after implantation for bioprosthetic valves have been associated with resolved valve degeneration and possible favourable clinical effects.

The current practice guidelines recommend that oral anticoagulation may be considered for 3 months after open surgical bioprosthetic valve implantation. Patients with an independent indication for oral anticoagulation (i.e. atrial fibrillation or venous thromboembolism) are recommended to continue this treatment lifelong, but there is no recommendation for oral anticoagulation following TAVI in patients without other indications. In patients without indication for oral anticoagulation, the use of double anti-platelet therapy for 3-6 months following TAVI is recommended. However, single anti-platelet therapy with acetylsalicylic acid (ASA) without clopidogrel has been reported to improve bleeding outcomes and a composite of bleeding and ischemic outcomes. The effect of on oral anticoagulation-based treatment strategy compared to the standard single anti-platelet treatment strategy for valve maintenance after TAVI is unknown.

Increased anti-thrombotic treatment intensity may come at the cost of increased bleeding risk. Dual anti-platelet therapy and combination therapy with anticoagulation and anti-platelet therapy have both been associated with unfavourable outcomes. Combined anti-platelet and anti-coagulation treatment has been shown to reduce valve degeneration at the cost of increased bleeding. Conversely, single anti-platelet therapy and anti-coagulation with a direct oral anti-coagulant (DOAC) have been associated with similar bleeding risk. Bleeding rates in patients treated with anti-coagulation after TAVI have been reported to be slightly higher than in patients treated with ASA after TAVI, but patients with conventional indications for anti-coagulation have higher baseline bleeding risk than those without such indications. Therefore, the risk of bleeding in patients treated with DOAC or ASA following TAVI may be similar, but no randomized trials have been performed.

ACASA-TAVI will include 360 patients > 65 years and < 80 years of age who have undergone successful TAVI and have no conventional indication for DOAC in a prospective randomized open-label blinded-endpoint (PROBE) study. The intervention arm will be 12 month therapy with an anti-Xa type DOAC (without antiplatelet therapy) and the active control arm will be standard dose ASA. After 12 months, the intervention group will be switched to ASA maintenance. All patients will undergo clinical assessment, cardiac CT and echocardiography at 12 months with blinded endpoint adjudication by an independent committee.

Outcome measures will comply with the Valve Academic Research Consortium 3 (VARC-3) consensus, and are described in detail in the protocol. The co-primary endpoints at 12 months, hypo-attenuated leaflet thickening (HALT) and safety composite, must both be met for the trial to declare success.

The effect of the DOAC therapy on long-term major adverse cardiovascular events (MACE) will be assessed after 5 years and 10 years.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Successful trans-catheter aortic valve implantation in patients aged >65 and <80 years old at the time of the procedure.

Exclusion criteria

  • Strict indication for anticoagulation or anti-platelet drugs
  • Strict contraindication for anticoagulation or anti-platelet drugs
  • Overt cognitive failure
  • Failure to obtain written informed consent
  • Concomitant use of inducers or inhibitors of CYP3A4 or P-glycoprotein

Treatment and study plan

acetylsalicylic acid

Drug

Acetylsalicylic acid 75 mg once daily is the current standard-of-care in TAVI patients without other indications for anticoagulation therapy.

Other names: B01A C06

Apixaban

Drug

Standard dose apixaban will be one of the options for the patients in the experimental arm.

Other names: B01A F02

Rivaroxaban

Drug

Standard dose rivaroxaban will be one of the options for the patients in the experimental arm.

Other names: B01A F01

Edoxaban

Drug

Standard dose edoxaban will be one of the options for the patients in the experimental arm.

Other names: B01A F03

Primary outcomes

  1. Hypo-attenuated leaflet thickening

    Time frame: 12 months

    First co-primary endpoint. The presence of hypo-attenuated leaflet thickening on dedicated cardiac CT after 12 months will be registered by a blinded expert reader. Intention-to-treat, superiority.

  2. Safety composite - Incidence of Treatment Emergent Adverse Clinical Outcome

    Time frame: 12 months

    Second co-primary outcome. Composite of VARC-3 bleeding events, thromboembolic events (myocardial infarction or stroke) and all-cause mortality. Per-protocol, non-inferiority.

  3. Major adverse cardiovascular events (MACE)

    Time frame: 5 years

    Primary outcome during long-term follow-up. The rate of the composite of Cardiac death, Aortic valve re-intervention, Stroke, Myocardial infarction, Heart failure hospitalization and Major, life-threatening, or disabling bleeding.

  4. Major adverse cardiovascular events (MACE)

    Time frame: 10 years

    Primary outcome during long-term follow-up. The rate of the composite of Cardiac death, Aortic valve re-intervention, Stroke, Myocardial infarction, Heart failure hospitalization and Major, life-threatening, or disabling bleeding.

Secondary outcomes

  1. Clinical efficacy

    Time frame: 12 months

    First hierarchical secondary outcome. Composite of of Freedom from all-cause mortality, Freedom from all stroke, Freedom from hospitalization for procedure- or valve-related causes, Freedom from KCCQ overall summary score <45 or decline from baseline of >10 points. Intention-to-treat, superiority.

  2. Safety composite, superiority

    Time frame: 12 months

    Second hierarchical secondary outcome. Composite of VARC-3 bleeding events, thromboembolic events (myocardial infarction or stroke) and all-cause mortality. Same endpoint as second co-primary outcome, but intention-to-treat, superiority.

  3. Thromboembolic events

    Time frame: 12 months

    Third hierarchical secondary outcome. Composite of myocardial infarction or stroke of any cause. Intention-to-treat population.

  4. Bleeding events

    Time frame: 12 months

    Fourth hierarchical secondary outcome. Bleeding events according to VARC-3 definitions. Intention-to-treat population.

  5. All-cause mortality

    Time frame: 12 months

    Fifth hierarchical secondary outcome. Intention-to-treat population.

  6. The number of adverse events

    Time frame: 12 months

    First secondary safety endpoint. Safety population.

  7. The number of serious adverse events

    Time frame: 12 months

    Second secondary safety endpoint. Safety population.

  8. Life-threatening or disabling bleeding

    Time frame: 12 months

    Third secondary safety endpoint. Safety population. VARC-3 definition.

  9. Major bleeding

    Time frame: 12 months

    Fourth secondary safety endpoint. Safety population. VARC-3 definition.

  10. Minor bleeding

    Time frame: 12 months

    Fifth secondary safety endpoint. Safety population. VARC-3 definition.

Other outcomes

  1. CT signs of valve degeneration

    Time frame: 12 months

    Exploratory outcome. Any evidence of reduced leaflet mobility, hypo-attenuated leaflet thickening or thrombus.

  2. Echocardiographic signs of valve degeneration

    Time frame: 12 months

    Exploratory outcome. Change in transaortic pressure gradient assessed by echocardiography.

  3. Cardiac function

    Time frame: 12 months

    Exploratory outcome. Change in left ventricular global longitudinal strain assessed by echocardiography.

  4. Non-procedure-related life-threatening or disabling bleeding

    Time frame: 12 months

    Exploratory outcome. VARC-3 definition.

  5. Number of major adverse clinical events

    Time frame: 12 months

    Exploratory outcome. Defined as stroke or transient ischemic attack of any cause, myocardial infarction, re-intervention on the aortic valve, death (cardiac, all-cause, non-cardiac) and heart failure hospitalization

  6. Troponin T

    Time frame: 12 months

    Exploratory outcome. Assessment of blood samples.

  7. N-terminal pro-B-type natriuretic peptide

    Time frame: 12 months

    Exploratory outcome. Assessment of blood samples.

  8. Infective endocarditis

    Time frame: 12 months

    Exploratory outcome. Definition by Duke criteria.

  9. Change in quality of life - Kansas City Cardiomyopathy Questionnaire

    Time frame: 12 months

    Exploratory outcome. Assessed by change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score (score 0-100, Higher value indicates better quality of life).

  10. Cognitive function

    Time frame: 12 months

    Exploratory outcome. Assessed by change in the Mini-cog score

  11. Clinical efficacy

    Time frame: 5 years

    Composite of of Freedom from all-cause mortality, Freedom from all stroke, Freedom from hospitalization for procedure- or valve-related causes, Freedom from KCCQ overall summary score <45 or decline from baseline of >10 points. Intention-to-treat, superiority.

  12. All-cause mortality

    Time frame: 5 years

    Fifth hierarchical secondary outcome. Intention-to-treat population.

  13. Echocardiographic signs of valve degeneration

    Time frame: 5 years

    Exploratory outcome. Change in transaortic pressure gradient assessed by echocardiography.

  14. Cardiac function

    Time frame: 5 years

    Exploratory outcome. Change in left ventricular global longitudinal strain assessed by echocardiography.

  15. N-terminal pro-B-type natriuretic peptide

    Time frame: 5 years

    Exploratory outcome. Assessment of blood samples.

  16. Troponin T

    Time frame: 5 years

    Exploratory outcome. Assessment of blood samples.

  17. Individual components of MACE

    Time frame: 5 years

    Exploratory outcome. Assessment of the individual components of MACE (the primary outcome at long-term follow-up).

  18. Change in quality of life - Kansas City Cardiomyopathy Questionnaire

    Time frame: 5 years

    Exploratory outcome. Assessed by change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score (score 0-100, Higher value indicates better quality of life).

  19. Cognitive function

    Time frame: 5 years

    Exploratory outcome. Assessed by change in the Mini-cog score

  20. Infective endocarditis

    Time frame: 5 years

    Exploratory outcome. Definition by Duke criteria.

  21. Clinical efficacy

    Time frame: 10 years

    Composite of of Freedom from all-cause mortality, Freedom from all stroke, Freedom from hospitalization for procedure- or valve-related causes, Freedom from KCCQ overall summary score <45 or decline from baseline of >10 points. Intention-to-treat, superiority.

  22. All-cause mortality

    Time frame: 10 years

    Fifth hierarchical secondary outcome. Intention-to-treat population.

  23. Echocardiographic signs of valve degeneration

    Time frame: 10 years

    Exploratory outcome. Change in transaortic pressure gradient assessed by echocardiography.

  24. Cardiac function

    Time frame: 10 years

    Exploratory outcome. Change in left ventricular global longitudinal strain assessed by echocardiography.

  25. N-terminal pro-B-type natriuretic peptide

    Time frame: 10 years

    Exploratory outcome. Assessment of blood samples.

  26. Troponin T

    Time frame: 10 years

    Exploratory outcome. Assessment of blood samples.

  27. Individual components of MACE

    Time frame: 10 years

    Exploratory outcome. Assessment of the individual components of MACE (the primary outcome at long-term follow-up).

  28. Change in quality of life - Kansas City Cardiomyopathy Questionnaire

    Time frame: 10 years

    Exploratory outcome. Assessed by change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score (score 0-100, Higher value indicates better quality of life).

  29. Cognitive function

    Time frame: 10 years

    Exploratory outcome. Assessed by change in the Mini-cog score

  30. Infective endocarditis

    Time frame: 10 years

    Exploratory outcome. Definition by Duke criteria.

Sponsors and collaborators

Lead sponsor

Oslo University Hospital

Other

Collaborators

  • University of Oslo

Registry information

Acronym: ACASA-TAVI

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Sep 5, 2021
Registry last updated
Jun 9, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.