Dual Antiplatelet Therapy Versus Oral Anticoagulation for a Short Time to Prevent Cerebral Embolism After TAVI (AUREA)

PHASE IV Study of Dual Antiplatelet Therapy Versus Oral Anticoagulation for a Short Time to Prevent Cerebral Embolism After Percutaneous Aortic Valve Implantation. Multicenter Randomized Clinical Trial

The purpose of this study is to determine the incidence of major vascular events (ischemic or haemorrhagics) at the third month after initiation of the antithrombotic treatment (oral anticoagulation or dual antiplatelet therapy) in both arms followed TAVI.

Study Overview

• Status: Completed
• Conditions: Stroke; Aortic Valve Stenosis
• Intervention / Treatment: Drug: aspirin+clopidogrel (Duoplavin)

Detailed Description

Transcatheter aortic valve implantation (TAVI) procedure using any of their vascular access is an option with proven benefit definitively for treatment of severe symptomatic aortic stenosis in patients considered unsuitable for conventional open heart surgery.

By avoiding the hemodynamic effects, cardiovascular and cerebral microembolic load of cardiopulmonary bypass circulation, it is assumed that the TAVI procedure is beneficial despite the risk of neurological complications. Currently antithrombotic therapy after the procedure is not standardized. International treatment guidelines recommends that post-operative patients with a conventional surgical aortic bioprosthesis maintain oral anticoagulation for 3 months after the procedure, unless otherwise noted for its continuation. Whereas some studies have postulated that in patients with aortic bioprostheses, dual antiplatelet therapy is as effective to prevent major cardiac and cerebrovascular events as oral anticoagulation, with a lower incidence of bleeding complications at 3 months of treatment, the investigators formulated the following hypothesis:

• There is a lower incidence of major cardiac and cerebrovascular events in patients with dual antiplatelet therapy compared to patients with oral anticoagulation for 3 months after implantation of an aortic bioprosthesis TAVI procedure.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 36201
    • Hospital clinico Universitario Bellvitge
  • Malaga, Spain, 36201
    • Hospital Clinico Universitario de Malaga
  • Guipúzcoa
    • San Sebastián, Guipúzcoa, Spain, 20014
      • Policlínica de Guipuzcoa.SA
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Hospital Universitario Alvaro Cunqueiro

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:

1. Adult patients (more than 18 years) with ability to understand and accept the participation in the clinical trial.
2. Patients with symptomatic degenerative severe aortic stenosis rejected for conventional surgical aortic valve replacement due to unacceptably high risk and accepted for TAVI procedure
3. Signed informed consent.
4. Patients who are not participating in any other clinical trial or research study.

Exclusion Criteria:

1. Patients under oral anticoagulation treatment
2. Patients who can not undergo MRI study
3. Recent stroke < 14 days prior, revascularized coronary artery disease or life expectancy < 12 months
4. Patients with proven allergy to aspirin, clopidogrel or acenocoumarol
5. Patients that after TAVI procedure can not undergo a regimen of dual antiplatelet therapy or oral anticoagulation for 3 months due to any new post-TAVI medical indication

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
Active Comparator: Duoplavin; Both active substances in DuoPlavin: clopidogrel and acetylsalicylic acid, are inhibitors of platelet aggregation. Clopidogrel stops the platelets aggregating by blocking ADP. Acetylsalicylic acid the platelets aggregating by blocking the prostaglandin cyclo oxygenase.	Drug: aspirin+clopidogrel (Duoplavin); 100 mg aspirin ;75 mg clopidogrel 3º months; Other Names: DUOPLAVIN (aspirin 100 mg + clopidogrel 75 mg).; SINTROM (ACENOCUMAROL).
Sham Comparator: acenocumarol	Drug: aspirin+clopidogrel (Duoplavin); 100 mg aspirin ;75 mg clopidogrel 3º months; Other Names: DUOPLAVIN (aspirin 100 mg + clopidogrel 75 mg).; SINTROM (ACENOCUMAROL).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the effectiveness of dual antiplatelet therapy versus oral anticoagulation for prevention of cerebral thromboembolism by the detection of new areas of cerebral infarction by Magnetic Resonance Imaging (MRI) 3 months after TAVI.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the incidence of new areas of cerebral infarction by MRI between the different routes of vascular access and the various valve devices.		1 hour before TAVI, 1 hour and 24 hours after TAVI
Identify the development of cognitive impairment after TAVI	By the application of: 1)Mini-Mental State Examination (MMSE); 2)SF 36 (spanish version); 3)The NIHSS (National Institute of Health Stroke Scale). The evaluation of the neurological tests will be performed by a certificated neurologist.	Pre-TAVI, and at 1º 3º and 6º month after TAVI
Evaluate the Quality of life after TAVI.	By the application of Euroquol EQ5.	Pre-TAVI, and at 1º; 3º and 6º month after TAVI.

Collaborators and Investigators

• Sponsor: Andres Iñiguez Romo, MD, PhD
• Investigators: Principal Investigator: Andres Iniguez Romo, MD;PHD, Hospital Universitario Alvaro Cunqueiro; Principal Investigator: Victor A. Jimenez Diaz, MD;Msc, Hospital clinico universitario Vigo; Principal Investigator: Mariano Larman Tellechea, MD, Policlínica de Guipuzcoa SA San Sebastián; Study Director: Pablo Juan Salvadores, Pharma,MPH, Hospital Universitario Alvaro Cunqueiro; Principal Investigator: Jose M. Hernandez, MD, Hospital Virgen de la Victoria

Publications and helpful links

General Publications

• Kahlert P, Knipp SC, Schlamann M, Thielmann M, Al-Rashid F, Weber M, Johansson U, Wendt D, Jakob HG, Forsting M, Sack S, Erbel R, Eggebrecht H. Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study. Circulation. 2010 Feb 23;121(7):870-8. doi: 10.1161/CIRCULATIONAHA.109.855866.
• Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010 Oct 21;363(17):1597-607. doi: 10.1056/NEJMoa1008232. Epub 2010 Sep 22.
• Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011 Jun 9;364(23):2187-98. doi: 10.1056/NEJMoa1103510. Epub 2011 Jun 5.
• Herrmann M, Vos P, Wunderlich MT, de Bruijn CH, Lamers KJ. Release of glial tissue-specific proteins after acute stroke: A comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke. 2000 Nov;31(11):2670-7. doi: 10.1161/01.str.31.11.2670.
• Dunning J, Versteegh M, Fabbri A, Pavie A, Kolh P, Lockowandt U, Nashef SA; EACTS Audit and Guidelines Committee. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg. 2008 Jul;34(1):73-92. doi: 10.1016/j.ejcts.2008.02.024. Epub 2008 Mar 28. Erratum In: Eur J Cardiothorac Surg. 2008 Oct;34(4):934.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): June 30, 2019
• Study Completion (Actual): June 30, 2019

Study Registration Dates

• First Submitted: June 19, 2012
• First Submitted That Met QC Criteria: July 12, 2012
• First Posted (Estimate): July 17, 2012

Study Record Updates

• Last Update Posted (Actual): August 9, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Anticoagulation; Antiplatelet
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Embolism and Thrombosis; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Intracranial Embolism and Thrombosis; Thromboembolism; Embolism; Aortic Valve Stenosis; Intracranial Embolism; Physiological Effects of Drugs; Neurotransmitter Agents; 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; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: MEIX-VALV-001; 2011-005784-24 (EudraCT Number)