AntiCoagulation Versus AcetylSalicylic Acid After Transcatheter Aortic Valve Implantation

NCT05035277 | Completed Phase 3 DMC

• 2 other identifiers: 2474002021-001554-61
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 3

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.

Conditions

Aortic Stenosis

Keywords

Transcatheter Aortic Valve Implantation; Transcatheter Aortic Valve Replacement; Antithrombotic therapy; Anticoagulation therapy; Antiplatelet therapy

Outcome Measures

Primary Outcomes (4)

• Hypo-attenuated leaflet thickening

  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.

  12 months

• Safety composite - Incidence of Treatment Emergent Adverse Clinical Outcome

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

  12 months

• Major adverse cardiovascular events (MACE)

  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.

  5 years

• Major adverse cardiovascular events (MACE)

  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.

  10 years

Secondary Outcomes (10)

• Clinical efficacy

  12 months

• Safety composite, superiority

  12 months

• Thromboembolic events

  12 months

• Bleeding events

  12 months

• All-cause mortality

  12 months

Other Outcomes (30)

• CT signs of valve degeneration

  12 months

• Echocardiographic signs of valve degeneration

  12 months

• Cardiac function

  12 months

Study Arms (2)

Acetylsalicylic acid

ACTIVE COMPARATOR

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

Drug: Acetylsalicylic acid

Direct oral anticoagulation (DOAC)

EXPERIMENTAL

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.

Drug: Apixaban; Drug: Rivaroxaban; Drug: Edoxaban

Interventions

Acetylsalicylic acid DRUG

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

Also known as: B01A C06

Acetylsalicylic acid

Apixaban DRUG

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

Also known as: B01A F02

Direct oral anticoagulation (DOAC)

Rivaroxaban DRUG

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

Also known as: B01A F01

Direct oral anticoagulation (DOAC)

Edoxaban DRUG

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

Also known as: B01A F03

Direct oral anticoagulation (DOAC)

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oslo University Hospital: lead
• University of Oslo: collaborator

Study Sites (3)

Oslo Univesity Hospital - Ullevål

Oslo, Oslo, 0424, Norway

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

Oslo University Hospital - Rikshospitalet

Oslo, 0772, Norway

Location

Related Publications (2)

• 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.

  PMID: 33871579 BACKGROUND

• 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.

  PMID: 37634655 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

Aspirin; apixaban; Rivaroxaban; edoxaban

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Thiophenes; Sulfur Compounds; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Øyvind H Lie, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Separate endpoint adjudication committee blinded to randomized allocation of patients to treatment groups
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Parallel group prospective randomized open blinded endpoint (PROBE) trial

Study Record Dates

• First Submitted: August 19, 2021
• First Posted: September 5, 2021
• Study Start: December 4, 2021
• Primary Completion: June 5, 2026
• Study Completion: June 5, 2026
• Last Updated: June 9, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Will be made available with the publication of the primary analysis and remain available for 1 year. Thereafter, it can be made available upon request.
• Access Criteria: Researchers and clinicians with valid medical questions to be addressed. The data will not be available for commercial use.

Locations

NO (3)