Platelet Reactivity After TAVI: A Multicenter Pilot Study

NCT02224066 | Completed Phase 4 DMC

• 2 other identifiers: MEIX-VALV-002REAC TAVI
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 7

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.

Conditions

Severe Aortic Valve Stenosis; Transcatheter Aortic Valve Implantation; Transcatheter Aortic Valve Replacement

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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).

  Three months after antiplatelet treatment initiation following procedure.

Secondary Outcomes (1)

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

  Six hours after antiplatelet treatment initiation following procedure.

Other Outcomes (1)

• 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.

  Three months after antiplatelet treatment initiation following procedure.

Study Arms (3)

Ticagrelor

EXPERIMENTAL

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

Drug: Ticagrelor 90 mg twice per day during three months following TAVI

Aspirin/Clopidogrel

ACTIVE COMPARATOR

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

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

Registry arm

NO INTERVENTION

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.

Interventions

Ticagrelor 90 mg twice per day during three months following TAVI DRUG

Ticagrelor

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

Aspirin/Clopidogrel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospital de Meixoeiro: lead

Study Sites (7)

Hospital Clinic Universitari Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Álvaro Cunqueiro

Vigo, Pontevedra, 36312, Spain

Location

Hospital Santa Creu i Sant Creu

Barcelona, 08026, Spain

Location

Hospital Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Related Publications (7)

• 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.

  PMID: 20961243 BACKGROUND

• 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.

  PMID: 21907949 BACKGROUND

• 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.

  PMID: 22443478 BACKGROUND

• 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.

  PMID: 23956980 BACKGROUND

• 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.

  PMID: 21875913 BACKGROUND

• 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.

  PMID: 22991347 BACKGROUND

• 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.

  PMID: 30621974 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

Ticagrelor; Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Andrés Iñiguez Romo, MD;Phd

  Xerencia de Xestión Integrada de Vigo

  PRINCIPAL INVESTIGATOR

• Victor A Jimenez Diaz, MD; Msc

  Xerencia de Xestión Integrada de Vigo

  PRINCIPAL INVESTIGATOR

• Pablo Juan Salvadores, Pharma; MPH

  Xerencia xestión integrada de Vigo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Cardiology Department, Hospital Alvaro Cunqueiro

Study Record Dates

• First Submitted: August 21, 2014
• First Posted: August 25, 2014
• Study Start: January 1, 2016
• Primary Completion: May 1, 2017
• Study Completion: August 1, 2018
• Last Updated: August 3, 2018

Record last verified: 2018-08

Locations

ES (7)