Single antiplatelet treatment with Ticagrelor or Aspirin after Transcatheter Aortic Valve Implantation: multicenter randomized clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Biomedica Galicia Sur

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

21 Jan 2022 → ongoing

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-509290-22-00

EudraCT number

2021-003927-13

ClinicalTrials.gov

NCT05283356

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Assessment of the safety and efficacy of Ticagrelor vs Aspirin in the incidence of Net Adverse Clinical Event (NACE) at 12 months after TAVI.NACE is a composite of:
1. All-cause mortality
2. Transient ischemic attack (TIA) or stroke
3. Myocardial infarction
4. Progressive angina leading to emergency evaluation, rehospitalization or new coronary angiography
5. Valve thrombosis
6. Claudication
7. Acute limb ischemia leading to hospitalization
8. Any bleeding

Secondary objectives 6

1. Key secondary efficacy endpoint: Subclinical valve thrombosis (SVT) 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 (performed only in pre-specified centers).
2. Key secondary safety endpoint: Major bleeding (type 2, 3 and 5) at 12 months after TAVI according BARC (Bleeding Academic Research Consortium).
3. 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).
4. Individual components of NACE at 12 months after TAVI.
5. Subgroup analysis: gender, age, valve type, comorbidities.
6. Development of a thrombotic and bleeding risk score for TAVI patients.

Conditions and MedDRA coding

Severe Symptomatic Aortic Stenosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

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 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: Diabetes Mellitus, the current WHO diagnostic criteria for diabetes should be maintained – fasting plasma glucose ≥ 7.0mmol/l (126mg/dl) or 2–h plasma glucose ≥ 11.1mmol/l (200mg/dl), or under treatment with an oral hypoglycemic or insulin  Prior coronary artery disease (STEMI, NSTEMI, stable angina, or others) documented by invasive or non-invasive ischemia screening tests or imaging study  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 11

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. For female participants, the participant must not be pregnant or lactating and must be of non-childbearing potential, confirmed at screening & eligibility visit by one of the following: (a) Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range. (b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered a irreversible surgical sterilization
8. Concomitant oral or intravenous therapy with potent inhibitors of cytochrome P450 3A (CYP3A) that cannot be suspended during the study. Section 13.1 Ticagrelor Overdose: any dose over the clinically intended dose.
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. All-cause mortality at 12 months after TAVI
2. Transient ischemic attack (TIA) or stroke at 12 months after TAVI
3. Myocardial infarction at 12 months after TAVI
4. Bleeding at 12 months after TAVI according BARC
5. Net Adverse Clinical Event(s)

Secondary endpoints 11

1. All major bleeding (type 2, 3 and 5) at 12 months after TAVI according BARC
2. Incidence of subclinical valve thrombosis (SVT) detected by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion (RLM) at 3 and 12 months after TAVI assessed by 4-dimensional computed tomography (4DCT) imaging (performed only in pre-specified centers)
3. Gender
4. Age
5. Valve type
6. Comorbilities
7. All-caused mortality at 12 months after TAVI
8. Stroke/TIA at 12 months after TAVI
9. Myocardial infarction at 12 months after TAVI
10. Progressive angina leading to emergency evaluation, rehospitalization or new coronary angiography at 12 months after TAVI
11. Thrombotic and bleeding risk score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Biomedica Galicia Sur

Sponsor organisation

Fundacion Biomedica Galicia Sur

Address

Carretera Clara Campoamor 341, Bloque Tecnico Planta 2 Bloque Tecnico Planta 2

City

Vigo

Postcode

36213

Country

Spain

Scientific contact point

Organisation

Fundacion Biomedica Galicia Sur

Contact name

Independent Clinical Research Unit

Public contact point

Organisation

Fundacion Biomedica Galicia Sur

Contact name

Cardiovascular Research Unit

Locations

3 EU/EEA countries · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications