Anticoagulation Alone Versus Anticoagulation and Aspirin Following Transcatheter Aortic Valve Interventions (1:1) (AVATAR)

Anticoagulation Alone Versus Anticoagulation and Aspirin Following Transcatheter Aortic Valve Interventions - an Open, Multicenter Randomized Controlled Trial With Two Parallel Arms (1:1)

The main objective of this study is to demonstrate that a single anticoagulant therapy is superior to a combination of anticoagulant and antiplatelet therapy on the net clinical benefit estimated at 12 months after a Transcatheter Aortic Valve Intervention (TAVI) according to BARC2 criteria (bleeding complications; Mehran et al 2011) and VARC2 (other complications; Kappetein et al 2012)..

Study Overview

• Status: Recruiting
• Conditions: Transcatheter Aortic Valve Replacement
• Intervention / Treatment: Drug: Vitamin K antagonist or direct oral anticoagulant treatment; Drug: Aspirin

Detailed Description

The secondary objectives of this study are to evaluate the following at 3 months, 6 months and 12 months after TAVI in both groups:

1. Mortality (all causes).
2. Cardiovascular mortality.
3. The occurrence of myocardial infarction.
4. The occurrence of stroke.
5. The occurrence of valve thrombosis.
6. The occurrence of major bleeding (BARC ≥ 3).
7. The occurrence of minor bleeding (2 ≤ BARC <3).
8. Treatment compliance.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Guillaume Cayla, MD, PhD; Phone Number: +33.(0)4.66.68.31.49; Email: guillaume.cayla@chu-nimes.fr
• Study Contact Backup: Name: Carey Suehs, PhD; Phone Number: +33.(0)4.66.68.67.88; Email: carey.suehs@chu-nimes.fr

Study Locations

• France
  • Montpellier, France, 34295
    • Recruiting
    • CHRU de Montpellier - Hôpital Arnaud de Villeneuve
    • Principal Investigator: Florence LECLERCQ, MD, PhD
    • Sub-Investigator: Jean-Christophe Macia, MD
  • Montpellier cedex 2, France, 34960
    • Recruiting
    • Clinique du Millenaire
    • Sub-Investigator: Christophe Piot, MD, PhD
    • Sub-Investigator: Gilles Levy, MD
    • Sub-Investigator: François Rivalland, MD
  • Nîmes Cedex 09, France, 30029
    • Recruiting
    • CHRU de Nîmes - Hôpital Universitaire Carémeau
    • Principal Investigator: Guillaume CAYLA, MD, PhD
    • Sub-Investigator: Laurent Schmutz, MD
  • Nîmes Cedex 1, France, 30032
    • Not yet recruiting
    • Hôpital Privé Les Franciscaines
    • Sub-Investigator: Eric Maupas, MD
  • Perpignan, France, 66000
    • Recruiting
    • Clinique Saint-Pierre
    • Sub-Investigator: Gabriel Robert, MD
  • Perpignan, France, 66046
    • Recruiting
    • CH de Perpignan - Hôpital Saint Jean
    • Sub-Investigator: Frédéric Targosz, MD
    • Sub-Investigator: Delphine Delseny, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient or his/her representative must have given free and informed consent and signed the consent
• The patient must be insured or beneficiary of a health insurance plan
• The patient is available for 12 months of follow-up
• The patient underwent a successful transcutaneous implant procedure for an aortic valve
• The patient required anticoagulant treatment (AVK or DOAC) excepted rivaroxaban the day of inclusion
• The patient is stable on anticoagulant treatment

Exclusion Criteria:

• The patient is participating in another study
• The patient is in an exclusion period determined by a previous study
• The patient or his/her representative refuses to sign the consent
• It is impossible to correctly inform the patient or his/her representative
• The patient is pregnant or breastfeeding
• The patient has a contraindication (or an incompatible drug association) for a treatment used in this study
• The patient had a coronary stent for less than 12 months
• The patient does not require treatment with aspirin or any other antiplatelet agent
• The patient has a history of aspirin allergy
• High bleeding risk; such as platelets <50,000 / mm3 during screening, Hb <8.5 g / dL, history of intracranial hemorrhage or subdural hematoma, major surgery, parenchymal organ biopsy or severe trauma within 30 days before inclusion, active gastrointestinal ulcer in the last 3 months;
• History of Stroke in the last 3 months;
• Moderate or severe liver affection associated with coagulopathy
• Active infectious endocarditis
• Active tumor treated at the time of inclusion associated with expected survival less than one year
• Not following countraindications specific to the molecules used fo the patients receiving DOAC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: vitamin K antagonist or Direct oral anticoagulant treatment; In this group, patients will receive monotherapy via anticoagulant (AVK or DOAC) excepted rivaroxaban; this treatment given corresponds to the anticoagulant treatment the patient was receiving before surgery. A data collection book for monitoring INR values and dates for the next 12 months is given to the patient. Intervention: anticoagulant	Drug: Vitamin K antagonist or direct oral anticoagulant treatment; The Vitamin K antagonist or direct oral anticoagulant treatment will be administered to obtain an International Normalized Ratio between 2 and 3 as recommended if the treatment is AVK. The Direct oral anticoagulant treatment : Apixaban 5 mg x2 or 2.5 mg X2, Edoxaban 30 ou 60 mg
Active Comparator: vitamin K antagonist or Direct oral anticoagulant + Aspirin; In this group, patients will receive combination therapy via anticoagulant (AVK or DOAC) and aspirin, whose daily dose is between 75 mg and 100 mg; the anticoagulant treatment administered corresponds to the anticoagulant treatment the patient was receiving before the procedure, monitored and adapted according to current recommendations. A data collection book for monitoring INR values and dates for the next 12 months is given to the patient. Intervention: anticoagulant Intervention: Aspirin	Drug: Vitamin K antagonist or direct oral anticoagulant treatment; The Vitamin K antagonist or direct oral anticoagulant treatment will be administered to obtain an International Normalized Ratio between 2 and 3 as recommended if the treatment is AVK. The Direct oral anticoagulant treatment : Apixaban 5 mg x2 or 2.5 mg X2, Edoxaban 30 ou 60 mg; Drug: Aspirin; Daily dose is between 75 mg and 100 mg. Allergic reactions to aspirin may be observed in rare cases. In case of suspicion of allergy, treatment with aspirin is stopped.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite outcome of the following events: death from any cause, myocardial infarction, stroke all causes, valve thrombosis and hemorrhage ≥ 2 as defined by the VARC 2 (Valve Academic Research Consortium scale).	Month 12

Secondary Outcome Measures

Outcome Measure	Time Frame
All cause death according to the VARC 2 criteria	month 1
All cause death according to the VARC 2 criteria	month 3
All cause death according to the VARC 2 criteria	month 6
All cause death according to the VARC 2 criteria	month 12
Death due to cardio-vascular causes according to the VARC 2 criteria	month 1
Death due to cardio-vascular causes according to the VARC 2 criteria	month 3
Death due to cardio-vascular causes according to the VARC 2 criteria	month 6
Death due to cardio-vascular causes according to the VARC 2 criteria	month 12
Myocardial infarction according to VARC 2 criteria	month 1
Myocardial infarction according to VARC 2 criteria	month 3
Myocardial infarction according to VARC 2 criteria	month 6
Myocardial infarction according to VARC 2 criteria	month 12
Stroke (all cause) according to the VARC 2 criteria	month 1
Stroke (all cause) according to the VARC 2 criteria	month 3
Stroke (all cause) according to the VARC 2 criteria	month 6
Stroke (all cause) according to the VARC 2 criteria	month 12
Valve thrombosis according to the VARC 2 criteria	Month 1
Valve thrombosis according to the VARC 2 criteria	Month 3
Valve thrombosis according to the VARC 2 criteria	Month 6
Valve thrombosis according to the VARC 2 criteria	Month 12
Major hemorrhage (BARC ≥ 3)	Month 1
Major hemorrhage (BARC ≥ 3)	Month 3
Major hemorrhage (BARC ≥ 3)	Month 6
Major hemorrhage (BARC ≥ 3)	Month 12
Minor hemorrhage (2 ≤ BARC < 3)	Month 1
Minor hemorrhage (2 ≤ BARC < 3)	Month 3
Minor hemorrhage (2 ≤ BARC < 3)	Month 6
Minor hemorrhage (2 ≤ BARC < 3)	Month 12
Observance / Modification of treatment (Questionnaire according to Girerd et al. 2001)	Month 1
Observance / Modification of treatment (Questionnaire according to Girerd et al. 2001)	Month 3
Observance / Modification of treatment (Questionnaire according to Girerd et al. 2001)	Month 6
Observance / Modification of treatment (Questionnaire according to Girerd et al. 2001)	Month 12

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Collaborators: Medtronic
• Investigators: Study Director: Guillaume Cayla, MD, PhD, Centre Hospitalier Universitaire de Nîmes

Publications and helpful links

General Publications

• Girerd X, Radauceanu A, Achard JM, Fourcade J, Tournier B, Brillet G, Silhol F, Hanon O. [Evaluation of patient compliance among hypertensive patients treated by specialists]. Arch Mal Coeur Vaiss. 2001 Aug;94(8):839-42. French.
• Kappetein AP, Head SJ, Genereux P, Piazza N, van Mieghem NM, Blackstone EH, Brott TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack MJ, Mehran R, Rodes-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. Eur Heart J. 2012 Oct;33(19):2403-18. doi: 10.1093/eurheartj/ehs255.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): February 2, 2023
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: April 7, 2016
• First Submitted That Met QC Criteria: April 12, 2016
• First Posted (Estimated): April 13, 2016

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: antivitamins K; direct oral anti-coagulant
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Aspirin; Vitamin K; Anticoagulants
• Other Study ID Numbers: LOCAL/2016/GC-01; 2016-000352-98 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No