Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis

NCT02664649 | Completed Phase 3 DMC

• 2 other identifiers: P1411022015-001676-21
• Study Type: interventional
• Target: 1,510
• Locations: 4 countries
• Sites: 4

Brief Summary

ATLANTIS is a multicenter, phase IIIb, prospective, open-label, randomized trial. The objective of this study is to demonstrate superiority of a strategy of anticoagulation with apixaban (Anti-Xa Group) as compared to the current standard of care in patients who have undergone a successful TAVI procedure. The randomization is stratified according to the presence or not of a mandatory indication for anticoagulation for a reason other than the TAVI procedure (e.g. atrial fibrillation or DVT/PE).

Conditions

Symptomatic Aortic Stenosis; Eligible for Transcatheter Aortic Valve Replacement

Keywords

TAVR; Apixaban; Anticoagulant; VKA; Antiplatelet therapy; Aortic stenosis

Outcome Measures

Primary Outcomes (1)

• Composite of death, myocardial infarction, stroke, systemic embolism, intracardiac or bioprosthesis thrombus, any episode of deep vein thrombosis or pulmonary embolism, life-threatening or disabling or major bleeding at one year follow-up.

  life-threatening or disabling or major bleeding defined according to VARC-2 definitions over one year follow-up.

  up to 13 months

Secondary Outcomes (5)

• Presence or not of an indication (other than TAVI) for anticoagulation described in the medical record.

  from screening to randomization

• First occurrence of any event of the following composite criteria: a) Death, MI, any stroke through one year of randomization, b) Death, any stroke/TIA or systemic embolism c) Each individual parameter of the primary endpoint

  up to 13 months

• Minor bleedings (BARC 2 or 3a)

  up to 13 months

• Any bleeding

  up to 13 months

• Any evidence for valve thrombosis including hypoattenuated leaflet thickening (HALT)

  up to 13 months

Study Arms (2)

Apixaban

EXPERIMENTAL

Investigational Product is open label apixaban 5 mg tablets taken orally two times a day for 12 months. Subjects with 2 or more of the following characteristics will take apixaban 2.5 mg tablets orally twice daily: age ≥80 years, body weight \<60 kg, serum creatinine ≥1.5 mg/dL \[133 μMol/L\]. \- Also, subjects with severe renal insufficiency \[calculated Creatinine Clearance (Cr.Cl.) (Cockroft-Gault) between 15-29 ml/min\] will take apixaban 2.5 mg tablets orally twice daily

Drug: Apixaban

Standard of care

ACTIVE COMPARATOR

VKA or Antiplatelet therapy

Drug: Standard of care

Interventions

Apixaban DRUG

Investigational Product is open label apixaban 5 mg tablets taken orally two times a day for 12 months. Subjects with 2 or more of the following characteristics will take apixaban 2.5 mg tablets orally twice daily: age ≥80 years, body weight \<60 kg, serum creatinine ≥1.5 mg/dL \[133 μMol/L\]. \- Also, subjects with severe renal insufficiency \[calculated Creatinine Clearance (Cr.Cl.) (Cockroft-Gault) between 15-29 ml/min\] will take apixaban 2.5 mg tablets orally twice daily

Also known as: Brand name : Eliquis drug class : anticoagulant, factor-Xa inhibitor

Apixaban

Standard of care DRUG

VKA or Antiplatelet therapy

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients after clinically successful TAVI procedures irrespective of prior antithrombotic treatment are eligible for randomization.
• Ability to understand and to comply with the study protocol.
• Written informed consent.
• Men and women ≥18 years of age.
• Creatinine Clearance \< 15mL/min (Cockcroft formula) or patient undergoing dialysis.
• Mechanical valves.
• Known severe mitral valve stenosis requiring an intervention.
• Unsuccessful TAVI requiring re-intervention.
• Ongoing major bleeding or vascular complication (patients may become candidate to the study once stabilized).
• Prior history of intracranial haemorrhage.
• Recent cerebro-vascular event (CVE) or transient ischemic attack on anticoagulant therapy (\<6 weeks).
• Cardiogenic shock manifested by low cardiac output, vasopressor or respiratory dependence, or mechanical hemodynamic support.
• Planned major surgery during follow-up defined as high-bleeding risk according to ESC/EHRA and requiring interruption of the study drug with bridging
• Concomitant medical illness (terminal malignancy) that is associated with expected survival less than one year.
• Concomitant use of prasugrel or ticagrelor.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Action Research Group: collaborator
• Bristol-Meyers Squibb & Pfizer: collaborator

Study Sites (4)

ACTION Study Group, Institut de Cardiologie, Centre Hospitalier Universitaire Pitié Salpêtrière (APHP), UPMC

Paris, 75013, France

Location

Division of Cardiology and Angiology II, University Heart Center Freiburg

Bad Krozingen, Südring 15, 79189, Germany

Location

Unità Operativa di Cardiologia Fondazione Gabriele Monasterio C.N.R.

Massa, Via Aurelia Sud, 54100, Italy

Location

Hospitalet de Llobregat-Hospital Universitari de Bellvitge

Barcelona, Cardiologia Feixa Llarga, S/n, 08907, Spain

Location

Related Publications (4)

• Montalescot G, Redheuil A, Vincent F, Desch S, De Benedictis M, Eltchaninoff H, Trenk D, Serfaty JM, Charpentier E, Bouazizi K, Prigent M, Guedeney P, Salloum T, Berti S, Cequier A, Lefevre T, Leprince P, Silvain J, Van Belle E, Neumann FJ, Portal JJ, Vicaut E, Collet JP; ATLANTIS Investigators of the ACTION Group. Apixaban and Valve Thrombosis After Transcatheter Aortic Valve Replacement: The ATLANTIS-4D-CT Randomized Clinical Trial Substudy. JACC Cardiovasc Interv. 2022 Sep 26;15(18):1794-1804. doi: 10.1016/j.jcin.2022.07.014. Epub 2022 Aug 31.

  PMID: 36137682 DERIVED

• Collet JP, Van Belle E, Thiele H, Berti S, Lhermusier T, Manigold T, Neumann FJ, Gilard M, Attias D, Beygui F, Cequier A, Alfonso F, Aubry P, Baronnet F, Ederhy S, Kasty ME, Kerneis M, Barthelemy O, Lefevre T, Leprince P, Redheuil A, Henry P, Portal JJ, Vicaut E, Montalescot G; ATLANTIS Investigators of the ACTION Group. Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial. Eur Heart J. 2022 Aug 1;43(29):2783-2797. doi: 10.1093/eurheartj/ehac242.

  PMID: 35583186 DERIVED

• Collet JP, Berti S, Cequier A, Van Belle E, Lefevre T, Leprince P, Neumann FJ, Vicaut E, Montalescot G. Oral anti-Xa anticoagulation after trans-aortic valve implantation for aortic stenosis: The randomized ATLANTIS trial. Am Heart J. 2018 Jun;200:44-50. doi: 10.1016/j.ahj.2018.03.008. Epub 2018 Mar 10.

  PMID: 29898848 DERIVED

• Piayda K, Zeus T, Sievert H, Kelm M, Polzin A. Subclinical leaflet thrombosis. Lancet. 2018 Mar 10;391(10124):937-938. doi: 10.1016/S0140-6736(18)30534-8. No abstract available.

  PMID: 29536857 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

apixaban; Factor Xa Inhibitors; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anticoagulants; Hematologic Agents; Therapeutic Uses; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Jean-Philippe COLLET

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: January 27, 2016
• Study Start: August 26, 2016
• Primary Completion: October 15, 2020
• Study Completion: October 15, 2020
• Last Updated: February 25, 2021

Record last verified: 2021-02

Locations

DE (1); FR (1); IT (1); ES (1)