Anticoagulation for Aortic Bioprosthesis (ANTIPRO)

Randomized Control Study of Anticoagulation With Warfarin Por Patients With Aortic Bioprosthesis vs Aspirin Only

This study evaluates the clinical and hemodynamic outcome in patients after aortic valve replacement. Half of the patients will receive warfarin + aspirin and the other half will receive only aspirin. The investigators will focus mainly on early bioprosthesis degeneration.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis; Aortic Valve Disease; Aortic Valve Insufficiency; Aortic Valve Regurgitation
• Intervention / Treatment: Drug: Warfarin; Drug: Aspirin

Detailed Description

Aortic bioprosthesis have the advantage that they do not require life-long anticoagulation. Current guidelines support the use of aspirin (AAS) 100 mg as a class I indication.

Current evidence, mainly derived from transaortic valve implantation (TAVI) patients, have shown that aortic bioprosthesis suffer subclinical thrombosis which may explain the increase in gradient and bioprosthetic degeneration. Anticoagulation in this cases improve leaflet mobility and decrease in gradient. Evidence supporting early anticoagulation in patients with aortic bioprosthesis is not as strong as in the case of mitral bioprosthesis. Nonetheless, current American Heart Association/American College of Cardiology (AHA/ACC) guidelines recommend (IIa) the use of warfarin for at least 3 months after aortic valve replacement.

The aim is to conduct a single blinded (echocardiographist) randomized control study in patients who receive an aortic bioprosthesis. Comparison will be performed between the use of warfarin + aspirin vs aspirin alone. Duration of anticoagulation will be for 3 months and patients follow-up for 1 year. Clinical and echocardiographic evaluation will be performed in every patients. Some patients will undergo Positron Emission Tomography (PET-Scan).

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• Uruguay
  • Montevideo, Uruguay
    • Centro Cardiovascular Universitario
  • Montevideo, Uruguay
    • Instituto Nacional de Cirugia Cardiaca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with indication of aortic valve replacement with porcine bioprosthesis

Exclusion Criteria:

• Concomitant mitral valve replacement
• Previous atrial fibrillation
• Previous use oral anticoagulation
• Contraindication for the use of oral anticoagulation (high risk of bleeding, intolerance, allergy)
• Jehovah witness
• Platelet count below 90,000.
• Liver disease

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: Warfarin; Warfarin will be started 48-72h after aortic valve replacement. Dose will be 5 mg daily in order to obtain an Internation normal ratio (INR) of 2-3. Warfarin treatment will continue for 3 months. Aspirin will be administered 100 mg daily.	Drug: Warfarin; Oral anticoagulation; Other Names: Choice; Drug: Aspirin; Antiplatelet treatment; Other Names: AAS
Active Comparator: Aspirin only; Aspirin will be started 48-72h after aortic valve replacement. Dose will be 100 mg daily. Patients who undergo coronary artery revascularization will receive 325 mg daily.	Drug: Aspirin; Antiplatelet treatment; Other Names: AAS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transprosthetic aortic gradient	Change in Transprosthetic mean gradient	3 months and 1 year
Change in New York Heart Association (NYHA) class	NYHA class	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major bleeding	number of patients admitted due to Genitourinary (GU) or Gastrointestinal (GI) bleeding, pericardial tamponade, pleural effusion	3 months and 1 year
Embolic events	Number of patients with cerebral and peripheral ischemic events	3 months and 1 year
Prosthetic leak	Change in severity of prosthetic and paraprosthetic leakage	3 months and 1 year

Collaborators and Investigators

• Sponsor: Instituto Nacional de Cirugia Cardiaca, Uruguay
• Collaborators: Universidad de la Republica
• Investigators: Principal Investigator: Victor Dayan, MD, PhD, Instituto Nacional de Cirugia Cardiaca; Principal Investigator: Diego Freire, MD, Centro Cardiovascular Universitario

Publications and helpful links

General Publications

• Fernandez A, Loza G, Parma G, Florio L, Estigarribia J, Soca G, Robaina R, Duran A, Brusich D, Dayan V. Early anticoagulation after aortic valve replacement with porcine bioprosthesis randomized control trial(ANTIPRO). Eur J Cardiothorac Surg. 2022 Oct 29:ezac507. doi: 10.1093/ejcts/ezac507. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): December 30, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: January 15, 2019
• First Submitted That Met QC Criteria: January 16, 2019
• First Posted (Actual): January 17, 2019

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: February 21, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: aortic valve replacement; anticoagulation; bioprosthesis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Aortic Valve Insufficiency; Aortic Valve Disease; 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; Anticoagulants; Aspirin; Warfarin
• Other Study ID Numbers: ANTIPRO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Study protocol.
• IPD Sharing Time Frame: From January 2019
• IPD Sharing Access Criteria: Protocol will be shared by email. Investigators interested should send email to the PI who will evaluate the solicitude.
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No