AntiCoagulation Versus AcetylSalicylic Acid After Transcatheter Aortic Valve Implantation

NCT ID: NCT05035277

Last Updated: 2022-11-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 360 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-04
• Study Completion Date: 2026-11-30

Brief Summary

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.

Detailed Description

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.

Conditions

Aortic Stenosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Acetylsalicylic acid

Patients in the active control arm will receive 75 mg acetylsalicylic acid once daily indefinitely.

Group Type: ACTIVE_COMPARATOR

Acetylsalicylic acid

Intervention Type: DRUG

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

Direct oral anticoagulation (DOAC)

Patients in the experimental arm will receive an anti Xa-type DOAC (apixaban, rivaroxaban or edoxaban) in approved therapeutic dose for 12 months. The choice of DOAC agent will be made by the treating clinician after discussion with the patient. After 12 months, these patients will abort DOAC therapy. Acetylsalicylic acid, 75 mg once daily will be started after DOAC discontinuation and continued indefinitely.

Group Type: EXPERIMENTAL

Apixaban

Intervention Type: DRUG

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

Rivaroxaban

Intervention Type: DRUG

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

Edoxaban

Intervention Type: DRUG

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

Interventions

Acetylsalicylic acid

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

Intervention Type: DRUG

Apixaban

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

Intervention Type: DRUG

Rivaroxaban

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

Intervention Type: DRUG

Edoxaban

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

Intervention Type: DRUG

Other Intervention Names

B01A C06; B01A F02; B01A F01; B01A F03

Eligibility Criteria

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

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Oslo

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Øyvind Lie

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Øyvind H Lie, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Oslo University Hospital

Locations

Haukeland University Hospital

Bergen, , Norway

Site Status: NOT_YET_RECRUITING

Oslo Univesity Hospital - Ullevål

Oslo, , Norway

Site Status: NOT_YET_RECRUITING

Oslo University Hospital - Rikshospitalet

Oslo, , Norway

Site Status: RECRUITING

Countries

Norway

Central Contacts

Øyvind H Lie, MD, PhD

Role: CONTACT

oyvlie@gmail.com

+4793429011

Facility Contacts

Jon Herstad, MD

Role: primary

jon.herstad@helse-bergen.no

Anders Opdahl, MD PhD

Role: primary

Øyvind Lie, MD PhD

Role: primary

oyvlie@gmail.com

+4793420911

References

VARC-3 WRITING COMMITTEE; Genereux P, Piazza N, Alu MC, Nazif T, Hahn RT, Pibarot P, Bax JJ, Leipsic JA, Blanke P, Blackstone EH, Finn MT, Kapadia S, Linke A, Mack MJ, Makkar R, Mehran R, Popma JJ, Reardon M, Rodes-Cabau J, Van Mieghem NM, Webb JG, Cohen DJ, Leon MB. Valve Academic Research Consortium 3: updated endpoint definitions for aortic valve clinical research. Eur Heart J. 2021 May 14;42(19):1825-1857. doi: 10.1093/eurheartj/ehaa799.

Reference Type: BACKGROUND

PMID: 33871579 (View on PubMed)

Dodgson CS, Beitnes JO, Klove SF, Herstad J, Opdahl A, Undseth R, Eek CH, Broch K, Gullestad L, Aaberge L, Lunde K, Bendz B, Lie OH. An investigator-sponsored pragmatic randomized controlled trial of AntiCoagulation vs AcetylSalicylic Acid after Transcatheter Aortic Valve Implantation: Rationale and design of ACASA-TAVI. Am Heart J. 2023 Nov;265:225-232. doi: 10.1016/j.ahj.2023.08.010. Epub 2023 Aug 25.

Reference Type: DERIVED

PMID: 37634655 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

2021-001554-61

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

247400

Identifier Type: -

Identifier Source: org_study_id