Single Antiplatelet Treatment With Ticagrelor or Aspirin After Transcatheter Aortic Valve Implantation

Aortic Valve Stenosis Clinical Trial

— REAC-TAVI2  

Official title:

Single Antiplatelet Treatment With Ticagrelor or Aspirin After Transcatheter Aortic Valve Implantation: Multicenter Randomized Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05283356
• Other study ID #: REAC-TAVI 2
• Secondary ID: 2021-003927-13
• Status: Recruiting
• Phase: Phase 4
• Start date: January 21, 2022
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2022
• Source: Fundacin Biomedica Galicia Sur
• Contact: Victor A Jiménez Díaz, MD, MPH
• Phone: +34986825564
• Email: victor.alfonso.jimenez.diaz[@]sergas.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The optimal pharmacological therapy after transcatheter aortic valve implantation (TAVI) to prevent valve thrombosis and reduce thromboembolic complications without significantly increasing the risk of bleeding is not yet fully defined and constitutes an important unmet clinical need. Recently, single antiplatelet therapy (SAPT) with Aspirin has been increasingly adopted to avoid bleeding early after TAVI compared with dual antiplatelet therapy. However, TAVI population is affected by a diversity of chronic pathologies that increase the risk of post-TAVI ischemic complications. Stroke is prevalent, especially peri- and early post-TAVI (<1-8% in the 1st year). Although peri-TAVI myocardial infarction (MI) is rare (1-3%), concomitant coronary artery disease (CAD), diabetes mellitus (DM), and peripheral vascular disease (PVD), is very frequent in the TAVI population, affecting around 30-70% of patients. In patients with CAD, the need to re-access the coronary arteries after TAVI is challenging and can be hampered by the trancatheter valve struts.

This is critical in TAVI patients with an acute coronary syndrome and in younger patients with long-life expectancy after TAVI. The use of a P2Y12 inhibitor provides significant ischemic protection in the in the coronary, cerebral and peripheral vascular territories compare to Aspirin. The use of a P2Y12 inhibitor as antiplatelet treatment can decrease the need for new coronary revascularizations and reduce the incidence of thromboembolic complications after TAVI.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1206
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures.

2. Adult patients (more than 18 years) with ability to understand and accept the participation in the clinical trial.

3. Patients with degenerative symptomatic severe aortic stenosis (AS) accepted for TAVI with any of the commercial approved TAVI devices after evaluation of the Heart Team of each center,and with at least one of the following comorbidities:

1. Diabetes Mellitus, the current WHO diagnostic criteria for diabetes should be maintained - fasting plasma glucose = 7.0mmol/l (126 mg/dl) or 2-h plasma glucose = 11.1mmol/l (200mg/dl), or under treatment with an oral hypoglycemic or insulin.

2. Prior coronary artery disease (STEMI, NSTEMI, stable angina, or others) documented by invasive or non-invasive ischemia screening tests or imaging study.

3. Prior peripheral arterial disease documented by invasive or non-invasive ischemia screening tests or imaging study.

4. Successful TAVI performed by any vascular access.

5. Patients who are not participating in any other clinical trial or research study (registries allowed).

Exclusion Criteria:

1. Patients under chronic oral anticoagulation for any specific pathology.

2. Patients that cannot undergo a regimen of single antiplatelet therapy after TAVI.

3. History of overt major bleeding or intracranial hemorrhage.

4. Active pathological bleeding.

5. History of ischemic stroke within the last 30 days prior TAVI.

6. Patients with documented severe hepatic insufficiency.

7. Known pregnancy, breast-feeding, or intend to become pregnant during the study period.

8. Concomitant oral or intravenous therapy with potent inhibitors of cytochrome P450 3A (CYP3A) that cannot be suspended during the study.

9. Patients randomized in another clinical trial with an investigational product or device over the past 30 days.

10. Patients who cannot attend follow-up visits scheduled in the study.

11. History of allergic reactions or intolerance to Ticagrelor or Aspirin or any of the excipients.

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic
• Severe Aortic Valve Stenosis
• Transcatheter Aortic Valve Implantation (TAVI)
• Transcatheter Aortic Valve Replacement (TAVR)

Intervention

Drug:
• Ticagrelor 60mg
Ticagrelor 60mg BID after TAVI

Locations

Country	Name	City	State
Spain	Hospital Alvaro Cunqueiro	Vigo	Pontevedra

Sponsors (1)

Lead Sponsor	Collaborator
Fundacin Biomedica Galicia Sur

Country where clinical trial is conducted

Spain, 

References & Publications (9)

Brouwer J, Nijenhuis VJ, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, Frambach P, De Bruyne B, van Houwelingen GK, Van Der Heyden JAS, Toušek P, van der Kley F, Buysschaert I, Schotborgh CE, Ferdinande B, van der Harst P, Roosen J, Peper J, Thielen FWF, Veenstra L, Chan Pin Yin DRPP, Swaans MJ, Rensing BJWM, van 't Hof AWJ, Timmers L, Kelder JC, Stella PR, Baan J, Ten Berg JM. Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med. 2020 Oct 8;383(15):1447-1457. doi: 10.1056/NEJMoa2017815. Epub 2020 Aug 30. — View Citation

Jimenez Diaz VA, Baz Alonso JA, Estevez Ojea O, Serantes Combo A, Rodriguez Paz CM, Iñiguez Romo A. Real-Time Detection of an Acute Cerebral Thrombotic Occlusion During a Transcatheter Valve Intervention. JACC Cardiovasc Interv. 2018 Jul 9;11(13):e103-e104. doi: 10.1016/j.jcin.2018.03.048. Epub 2018 Jun 13. — View Citation

Jimenez Diaz VA, Lozano I, Baz Alonso JA, Calvo Iglesias F, Iñiguez Romo A. HALT After TAVR: Searching the Bases, Finding the Cusp. JACC Cardiovasc Interv. 2019 May 13;12(9):894-895. doi: 10.1016/j.jcin.2019.02.011. — View Citation

Jimenez Diaz VA, Lozano I, Tello Montoliu A, Baz Alonso JA, Iñiguez Romo A. Is There a Link Between Stroke, Anticoagulation, and Platelet Reactivity?: The Multifactorial Stroke Mechanism Following TAVR. JACC Cardiovasc Interv. 2019 Dec 23;12(24):2560-2561. doi: 10.1016/j.jcin.2019.10.004. — View 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 — View Citation

Jimenez Diaz VA, Tello-Montoliu A, Moreno R, Cruz Gonzalez I, Iñiguez Romo A. Reply: The REAC-TAVI Trial: Better Antiplatelet Therapy, Less Haze on the Horizon. JACC Cardiovasc Interv. 2019 Apr 22;12(8):803-804. doi: 10.1016/j.jcin.2019.02.038. — View Citation

Kim WK, Pellegrini C, Ludwig S, Möllmann H, Leuschner F, Makkar R, Leick J, Amat-Santos IJ, Dörr O, Breitbart P, Jimenez Diaz VA, Dabrowski M, Rudolph T, Avanzas P, Kaur J, Toggweiler S, Kerber S, Ranosch P, Regazzoli D, Frank D, Landes U, Webb J, Barbanti M, Purita P, Pilgrim T, Liska B, Tabata N, Rheude T, Seiffert M, Eckel C, Allali A, Valvo R, Yoon SH, Werner N, Nef H, Choi YH, Hamm CW, Sinning JM. Feasibility of Coronary Access in Patients With Acute Coronary Syndrome and Previous TAVR. JACC Cardiovasc Interv. 2021 Jul 26;14(14):1578-1590. doi: 10.1016/j.jcin.2021.05.007. — View Citation

Trejo-Velasco B, Cruz-González I, Tello-Montoliu A, Baz-Alonso JA, Salvadores PJ, Moreno R, Romaguera R, Molina-Navarro E, Paredes-Galán E, De-Miguel-Castro A, Bastos-Fernandez G, Ortiz-Saez A, Fernández-Barbeira S, Iñiguez-Romo A, Jimenez-Diaz VA. Influe — View Citation

Trejo-Velasco B, Tello-Montoliu A, Cruz-González I, Moreno R, Baz-Alonso JA, Salvadores PJ, Romaguera R, Molina-Navarro E, Paredes-Galán E, Fernández-Barbeira S, Ortiz-Saez A, Bastos-Fernandez G, De Miguel-Castro A, Figueiras-Guzman A, Iñiguez-Romo A, Jim — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and efficacy of Ticagrelor vs Aspirin in the incidence of NACE at 12 months after TAVI.	NACE is a composite of: all-cause mortality, transient ischemic attack (TIA) or stroke, myocardial infarction, progressive angina leading to emergency evaluation,rehospitalization or new coronary angiography, valve thrombosis, claudication, acute limb ischemia leading to hospitalization, any bleeding.	12 months
Secondary	Efficacy endpoint: Subclinical valve thrombosis	Detected by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion(RLM) at 3 and 12 months after TAVI assessed by 4-dimensional computed tomography (4D-CT) imaging.; HALT: Hypoattenuating thickening in typically meniscal configuration on one or more leaflets, with or without RLM. The extent of HALT should be described per leaflet, using a 4-tier grading scale in regard to leaflet involvement along the curvilinear contour, assuming maximum involvement at the base of the leaflet: =25% (limited to the base) >25% and =50% >50% and =75% >75% Inconclusive for HALT: imaging with insufficient image quality or presence of artifact RLM: The extent of RLM should be described per leaflet, using a 4-tier grading scale None: no reduction in leaflet excursion <50% reduction in leaflet excursion; =50% reduction in leaflet excursion Immobile: immobile leaflet Inconclusive for RLM: imaging with insufficient image quality or presence of artefact	3 and 12 months
Secondary	Safety endpoint: Major bleeding	Major bleeding (type 2, 3 and 5) at 12 months after TAVI according BARC (Bleeding Academic Research Consortium)	12 months
Secondary	Patient-oriented composite endpoints	Patient-oriented composite endpoints (POCE) at 12 months after TAVI (POCE is a composite of all-cause mortality,TIA/stroke, myocardial infarction, progressive angina leading to emergency evaluation, rehospitalization or new coronary angiography).	12 months