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

• ClinicalTrials.gov Identifier: NCT01642134
• Recruitment Status: Completed
• First Posted: July 17, 2012
• Last Update Posted: August 9, 2019
• Sponsor: Andres Iñiguez Romo, MD, PhD
• Information provided by (Responsible Party): Andres Iñiguez Romo, MD, PhD, Hospital de Meixoeiro

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Aortic Valve Stenosis; Stroke	Drug: aspirin+clopidogrel (Duoplavin)	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2013
• Actual Primary Completion Date: June 30, 2019
• Actual Study Completion Date: June 30, 2019

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 3 months ]

Secondary Outcome Measures :

1. Determine the incidence of new areas of cerebral infarction by MRI between the different routes of vascular access and the various valve devices. [ Time Frame: 1 hour before TAVI, 1 hour and 24 hours after TAVI ]
2. Identify the development of cognitive impairment after TAVI [ Time Frame: Pre-TAVI, and at 1º 3º and 6º month 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.
3. Evaluate the Quality of life after TAVI. [ Time Frame: Pre-TAVI, and at 1º; 3º and 6º month after TAVI. ]
   By the application of Euroquol EQ5.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Spain

Policlínica de Guipuzcoa.SA

San Sebastián, Guipúzcoa, Spain, 20014

Hospital Universitario Álvaro Cunqueiro

Vigo, Pontevedra, Spain, 36312

Hospital clinico Universitario Bellvitge

Barcelona, Spain, 36201

Hospital Clinico Universitario de Malaga

Malaga, Spain, 36201

Sponsors and Collaborators

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 Álvaro Cunqueiro
• Principal Investigator: Jose M. Hernandez, MD; Hospital Virgen de la Victoria

More Information

Additional Information:

Related Info 

Publications:

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.

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.

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.

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.

• Responsible Party: Andres Iñiguez Romo, MD, PhD, MD; PHD, Hospital de Meixoeiro
• ClinicalTrials.gov Identifier: NCT01642134
• Other Study ID Numbers: MEIX-VALV-001; 2011-005784-24 ( EudraCT Number )
• First Posted: July 17, 2012
• Last Update Posted: August 9, 2019
• Last Verified: August 2019

Keywords provided by Andres Iñiguez Romo, MD, PhD, Hospital de Meixoeiro:

Antiplatelet; Anticoagulation

Additional relevant MeSH terms:

Intracranial Embolism; Embolism; Aortic Valve Stenosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Ventricular Outflow Obstruction; Intracranial Embolism and Thrombosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Thromboembolism; Aspirin; Clopidogrel; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors