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Platelet Reactivity After TAVI: A Multicenter Pilot Study (REAC-TAVI)

Primary Purpose

Severe Aortic Valve Stenosis, Transcatheter Aortic Valve Implantation, Transcatheter Aortic Valve Replacement

Status

Completed

Phase

Phase 4

Locations

Spain

Study Type

Interventional

Intervention

Ticagrelor 90 mg twice per day during three months following TAVI

Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI

About this trial

This is an interventional treatment trial for Severe Aortic Valve Stenosis focused on measuring Aortic stenosis, TAVI, TAVR, Transcatheter aortic valve implantation, Ticagrelor, Antiplatelet reactivity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

For inclusion in the study subjects should fulfill the following criteria:

Provision of informed consent prior to any study specific procedures.
Adult patients (more than 18 years) with ability to understand and accept the participation in the clinical trial.
Patients with degenerative symptomatic severe AS accepted for TAVI after evaluation of the Heart Team of each center.
Patients who are not participating in any other clinical trial or research study (registries allowed).

Exclusion Criteria:

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

Recent stroke <14 days prior to TAVI, non-revascularized severe coronary or carotid artery disease (>70% stenosis) or life expectancy < 12 months
Patients under chronic oral anticoagulation
Patients with proven allergy to aspirin, clopidogrel or ticagrelor
Patients that after TAVI cannot undergo a regimen of single or dual antiplatelet therapy for 3 months due to a new post-TAVI medical indication
Known pregnancy or breast-feeding
Concomitant oral or intravenous therapy with potent inhibitors of cytochrome P450 3A (CYP3A) that cannot be suspended during the course of the study. Medications considered as potent inhibitors are: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (or erythromycin but not astromicin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and more than a daily liter of grapefruit juice.
Thrombocytopenia (<50,000 platelets U/L) well documented and clinically relevant.
Patients with documented moderate or severe hepatic insufficiency
Any condition that may put the patient at risk or influence the outcome of the trial
Patients previously randomized in this trial or in another clinical trial with an investigational product or device over the past 30 days.
Patients who cannot attend follow up visits scheduled in the study

Sites / Locations

Hospital Clinic Universitari Bellvitge
Hospital Universitario Álvaro Cunqueiro
Hospital Santa Creu i Sant Creu
Hospital Virgen de las Nieves
Hospital Universitario La Paz
Hospital Universitario Virgen de la Arrixaca
Hospital Universitario de Salamanca

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

No Intervention

Arm Label

Ticagrelor

Aspirin/Clopidogrel

Registry arm

Arm Description

Patients with high-on-treatment platelet reactivity (PRU ≥ 208)

Patients with normal-on-treatment platelet reactivity (PRU < 208) will continue with Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI.

Outcomes

Primary Outcome Measures

Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by a system to verify the patient's platelet reactivity (VerifyNow P2Y12 assay).

Secondary Outcome Measures

Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by VerifyNow P2Y12 assay.

Full Information

NCT ID

NCT02224066

First Posted

August 21, 2014

Last Updated

August 1, 2018

Sponsor

Hospital de Meixoeiro

1. Study Identification

Unique Protocol Identification Number

NCT02224066

Brief Title

Platelet Reactivity After TAVI: A Multicenter Pilot Study

Acronym

REAC-TAVI

Official Title

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Implantation

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

January 2016 (Actual)

Primary Completion Date

May 2017 (Actual)

Study Completion Date

August 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Hospital de Meixoeiro

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

A high platelet reactivity in patients with severe symptomatic Aortic Stenosis (AS) selected for TAVI (Transcatheter aortic valve implantation) procedure has been demonstrated previously, and the use of double antiaggregation therapy (DAPT) with Clopidogrel and Acetylsalicylic acid (ASA) do not achieve consistent and adequate suppression of platelet reactivity. The purpose of this study is evaluate the efficacy of ticagrelor alone versus DAPT with clopidogrel and aspirin for the suppression of high platelet reactivity following TAVI.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Aortic Valve Stenosis, Transcatheter Aortic Valve Implantation, Transcatheter Aortic Valve Replacement

Keywords

Aortic stenosis, TAVI, TAVR, Transcatheter aortic valve implantation, Ticagrelor, Antiplatelet reactivity

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ticagrelor

Arm Type

Experimental

Arm Description

Patients with high-on-treatment platelet reactivity (PRU ≥ 208)

Arm Title

Aspirin/Clopidogrel

Arm Type

Active Comparator

Arm Description

Patients with high-on-treatment platelet reactivity (PRU ≥ 208)

Arm Title

Registry arm

Arm Type

No Intervention

Arm Description

Patients with normal-on-treatment platelet reactivity (PRU < 208) will continue with Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI.

Intervention Type

Drug

Intervention Name(s)

Ticagrelor 90 mg twice per day during three months following TAVI

Intervention Type

Drug

Intervention Name(s)

Aspirin 100 mg plus Clopidogrel 75 mg daily during three months following TAVI

Primary Outcome Measure Information:

Title

Time Frame

Three months after antiplatelet treatment initiation following procedure.

Secondary Outcome Measure Information:

Title

Evaluate the effectiveness of ticagrelor compared to clopidogrel and aspirin for the suppression of residual platelet reactivity by VerifyNow P2Y12 assay.

Time Frame

Six hours after antiplatelet treatment initiation following procedure.

Other Pre-specified Outcome Measures:

Title

Assess the safety of antiplatelet monotherapy with ticagrelor compared to DAPT with aspirin and clopidogrel, with regard to the incidence of investigator-reported clinical events according to predefined criteria, including bleeding definitions.

Time Frame

Three months after antiplatelet treatment initiation following procedure.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: For inclusion in the study subjects should fulfill the following criteria: Provision of informed consent prior to any study specific procedures. Adult patients (more than 18 years) with ability to understand and accept the participation in the clinical trial. Patients with degenerative symptomatic severe AS accepted for TAVI after evaluation of the Heart Team of each center. Patients who are not participating in any other clinical trial or research study (registries allowed). Exclusion Criteria: Subjects should not enter the study if any of the following exclusion criteria are fulfilled: Recent stroke <14 days prior to TAVI, non-revascularized severe coronary or carotid artery disease (>70% stenosis) or life expectancy < 12 months Patients under chronic oral anticoagulation Patients with proven allergy to aspirin, clopidogrel or ticagrelor Patients that after TAVI cannot undergo a regimen of single or dual antiplatelet therapy for 3 months due to a new post-TAVI medical indication Known pregnancy or breast-feeding Concomitant oral or intravenous therapy with potent inhibitors of cytochrome P450 3A (CYP3A) that cannot be suspended during the course of the study. Medications considered as potent inhibitors are: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (or erythromycin but not astromicin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and more than a daily liter of grapefruit juice. Thrombocytopenia (<50,000 platelets U/L) well documented and clinically relevant. Patients with documented moderate or severe hepatic insufficiency Any condition that may put the patient at risk or influence the outcome of the trial Patients previously randomized in this trial or in another clinical trial with an investigational product or device over the past 30 days. Patients who cannot attend follow up visits scheduled in the study

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrés Iñiguez Romo, MD;Phd

Organizational Affiliation

Xerencia de Xestión Integrada de Vigo

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Victor A Jimenez Diaz, MD; Msc

Organizational Affiliation

Xerencia de Xestión Integrada de Vigo

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Pablo Juan Salvadores, Pharma; MPH

Organizational Affiliation

Xerencia xestión integrada de Vigo

Official's Role

Study Director

Facility Information:

Facility Name

Hospital Clinic Universitari Bellvitge

City

Hospitalet de Llobregat

State/Province

Barcelona

ZIP/Postal Code

08907

Country

Spain

Facility Name

Hospital Universitario Álvaro Cunqueiro

City

Vigo

State/Province

Pontevedra

ZIP/Postal Code

36312

Country

Spain

Facility Name

Hospital Santa Creu i Sant Creu

City

Barcelona

ZIP/Postal Code

08026

Country

Spain

Facility Name

Hospital Virgen de las Nieves

City

Granada

ZIP/Postal Code

18014

Country

Spain

Facility Name

Hospital Universitario La Paz

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Hospital Universitario Virgen de la Arrixaca

City

Murcia

ZIP/Postal Code

30120

Country

Spain

Facility Name

Hospital Universitario de Salamanca

City

Salamanca

ZIP/Postal Code

37007

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

20961243

Citation

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.

Results Reference

background

PubMed Identifier

21907949

Citation

Ussia GP, Scarabelli M, Mule M, Barbanti M, Sarkar K, Cammalleri V, Imme S, Aruta P, Pistritto AM, Gulino S, Deste W, Capodanno D, Tamburino C. Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation. Am J Cardiol. 2011 Dec 15;108(12):1772-6. doi: 10.1016/j.amjcard.2011.07.049. Epub 2011 Sep 10.

Results Reference

background

PubMed Identifier

22443478

Citation

Makkar RR, Fontana GP, Jilaihawi H, Kapadia S, Pichard AD, Douglas PS, Thourani VH, Babaliaros VC, Webb JG, Herrmann HC, Bavaria JE, Kodali S, Brown DL, Bowers B, Dewey TM, Svensson LG, Tuzcu M, Moses JW, Williams MR, Siegel RJ, Akin JJ, Anderson WN, Pocock S, Smith CR, Leon MB; PARTNER Trial Investigators. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. 2012 May 3;366(18):1696-704. doi: 10.1056/NEJMoa1202277. Epub 2012 Mar 26. Erratum In: N Engl J Med. 2012 Aug 30;367(9):881.

Results Reference

background

PubMed Identifier

23956980

Citation

Tousek P, Kocka V, Sulzenko J, Bednar F, Linkova H, Widimsky P. Pharmacodynamic effect of clopidogrel in patients undergoing transcatheter aortic valve implantation. Biomed Res Int. 2013;2013:386074. doi: 10.1155/2013/386074. Epub 2013 Jul 15.

Results Reference

background

PubMed Identifier

21875913

Citation

Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation. 2011 Sep 6;124(10):1132-7. doi: 10.1161/CIRCULATIONAHA.111.029165. Epub 2011 Aug 29.

Results Reference

background

PubMed Identifier

22991347

Citation

Husted S, James S, Becker RC, Horrow J, Katus H, Storey RF, Cannon CP, Heras M, Lopes RD, Morais J, Mahaffey KW, Bach RG, Wojdyla D, Wallentin L; PLATO study group. Ticagrelor versus clopidogrel in elderly patients with acute coronary syndromes: a substudy from the prospective randomized PLATelet inhibition and patient Outcomes (PLATO) trial. Circ Cardiovasc Qual Outcomes. 2012 Sep 1;5(5):680-8. doi: 10.1161/CIRCOUTCOMES.111.964395.

Results Reference

background

PubMed Identifier

30621974

Citation

Jimenez Diaz VA, Tello-Montoliu A, Moreno R, Cruz Gonzalez I, Baz Alonso JA, Romaguera R, Molina Navarro E, Juan Salvadores P, Paredes Galan E, De Miguel Castro A, Bastos Fernandez G, Ortiz Saez A, Fernandez Barbeira S, Raposeiras Roubin S, Ocampo Miguez J, Serra Penaranda A, Valdes Chavarri M, Cequier Fillat A, Calvo Iglesias F, Iniguez Romo A. Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement: The REAC-TAVI Trial. JACC Cardiovasc Interv. 2019 Jan 14;12(1):22-32. doi: 10.1016/j.jcin.2018.10.005.

Results Reference

derived

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Platelet Reactivity After TAVI: A Multicenter Pilot Study

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