Severe Aortic Valve Stenosis, Aortic Valve Stenosis, Transcatheter Aortic Valve Replacement (TAVR), Transcatheter Aortic Valve Implantation (TAVI)
Conditions
Keywords
Severe Aortic Valve Stenosis, Transcatheter aortic valve replacement (TAVR), Transcatheter aortic valve implantation (TAVI), Single antiplatelet therapy (SAPT), Ticagrelor 60 mg, ASA 100 mg, Bleeding, Valve thrombosis
Brief 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.
Interventions
DRUGTicagrelor 60mg
Ticagrelor 60mg BID after TAVI
Sponsors
Fundacin Biomedica Galicia Sur
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and efficacy of Ticagrelor vs Aspirin in the incidence of NACE at 12 months after TAVI. | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy endpoint: Subclinical valve thrombosis | 3 and 12 months | 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 |
| Safety endpoint: Major bleeding | 12 months | Major bleeding (type 2, 3 and 5) at 12 months after TAVI according BARC (Bleeding Academic Research Consortium) |
| Patient-oriented composite endpoints | 12 months | 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). |
Countries
Spain
Contacts
Primary ContactVictor A Jiménez Díaz, MD, MPH
Backup ContactPablo Juan-Salvadores, Pharma, MPH, PhD
Outcome results
None listed