Safety Profile Evaluation of TICagrelor Alone Compared to a Combination of Lysine Acetylsalicylate-Clopidogrel in the Context of Transcatheter Aortic Valve Implantation (TAVI)

University Hospital, Bordeaux50 enrolled

Overview

Transcatheter Aortic Valve Implantation (TAVI) is now the method of choice to treat aortic stenosis in old and frail patients. Antiplatelet therapy must be associated for the procedure and during few weeks after implantation in the aim to minimize cerebral embolization. But for now, the best antiplatelet regimen has to be determined. In this context, investigators want to evaluate the safety of use of ticagrelor alone versus standardized therapy which involves lysine acetylsalicylate and clopidogrel. In this study, we will randomly compare 154 patients in each group in terms of early safety (30 days) after the procedure.

In spite of the use of the combination of lysine acetylsalicylate and clopidogrel during and after the procedure of TAVI, rates of stroke remains high, between 4 and 10% regarding the studies and registries. None of the therapeutics have regulatory authorisation for this indication. On the other hand, the rates of bleeding events are also high in this old and frail population. That is why, considering its pharmacological specificity, investigators hypothesize that ticagrelor, used alone, could be non-inferior on safety criteria than the combination of lysine acetylsalicylate and clopidogrel. Our study want to evaluate the safety profile of Ticagrelor alone (180 mg loading dose before intervention and 90 mg twice daily during 30 days after the procedure) compared to the standardized treatment combining lysine acetylsalicylate (75 mg before and 75 mg daily after the procedure) and clopidogrel (300mg loading dose before and 75 mg daily after the procedure). Patients will be followed during one month. Then they will be all placed under the usual antiplatelet treatment (clopidogrel and lysine acetylsalicylate for two additional months and then lysine acetylsalicylate alone lifelong).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Provision of informed consent prior to any study specific procedures * Female or male aged \> 18 years * Patient eligible for TAVI as recommended by French health care system authority (HAS) Exclusion Criteria: * Allergy, hypersensitivity, or contraindication to lysine acetylsalicylate, clopidogrel, ticagrelor, any anticoagulation or magnetic resonance imaging (MRI) or CT-scanner contrast agents * Use of Cytochrome P3a (CYP3a) inhibitor * Need for chronic anticoagulation * Previous percutaneous coronary intervention or acute coronary syndrome requiring dual antiplatelet therapy * Previous cardiac surgery for valve replacement * Prior stroke, transient ischemic attack (TIA) or known carotid stenosis \> 70% * Active pathological bleeding or gastric ulcer \< 3month * Known thrombocytopenia, anemia or any coagulopathy * Severe kidney or hepatic impairment * Hemodynamic instability * Refusal of Transfusion * Significant mental impairment * Inability to give informed consent or comply with study related procedures or high likelihood of being unavailable for follow-up * Pregnant or breastfeeding women * Women of childbearing potential without effective contraception (oestroprogestative, intrauterine devices) * Participant in another investigational drug or device study.

Locations (5)

CHRU de Lille

Lille, France

APHM

Marseille, France

CHRU de Nîmes

Nîmes, France

APHP

Paris, France

CHU de Bordeaux

Pessac, France

Outcomes

Primary Outcomes

Number of patient presenting at least one event of the Valve Academic Research Consortium-2 (VARC2) composite endpoint

VARC2 composite endpoint : * All-cause mortality * All stroke (disabling and non-disabling) * Life-threatening or disabling bleeding * Acute kidney injury - Stage 2 or 3 (including renal replacement therapy) * Coronary artery obstruction requiring intervention * Major vascular complication * Valve-related dysfunction requiring repeat procedure

Time frame: Day 30

Number of patient died

Time frame: Day 30

Number of patient presenting stroke or Transient Ischemic Attack (TIA)

Diagnostic criteria: Acute episode of a focal or global neurological deficit with at least one of the following: change in the level of consciousness, hemiplegia, hemiparesis, numbness, or sensory loss affecting one side of the body, dysphasia or aphasia, hemianopia, amaurosis fugax, or other neurological signs or symptoms consistent with stroke Stroke: duration of a focal or global neurological deficit \>24 h; OR \<24 h if available neuroimaging documents a new haemorrhage or infarct; OR the neurological deficit results in death TIA: duration of a focal or global neurological deficit \<24 h, any variable neuroimaging does not demonstrate a new hemorrhage or infarct

Time frame: Day 30

Number of patient presenting life-threatening bleeding

Life-threatening bleeding: Fatal bleeding OR Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating pericardiocentesis, or intramuscular with compartment syndrome OR Bleeding causing hypovolaemic shock or severe hypotension requiring vasopressors or surgery OR Overt source of bleeding with drop in haemoglobin \>5 g/dL or whole blood or packed red blood cells (RBCs) transfusion \>4 units

Time frame: Day 30

Number of patients presenting post-TAVI acute kidney failure stage 2 or 3 as assessed by VARC2

Time frame: Day 30

Number of patients presenting angiographic or echographic evidence of a new, partial or complete, obstruction of a coronary ostium, either by the valve prosthesis itself, the native leaflets, calcifications, or dissection

Time frame: Day 30

Number of patients presenting major vascular complications

Time frame: Day 30

Number of patients requiring a new procedure like Balloon Aortic valvuloplasty (BAV), new procedure of TAVI or Surgical aortic valve replacement (SAVR)

Time frame: Day 30

Secondary Outcomes

Number of patients presenting at least one conduction disturbance or arrhythmias

Time frame: Day 30

Number of patients presenting at least one other TAVI related complication

Time frame: Day 30

Number of patients presenting at least one bleeding event (life-threatening, major or minor)

Time frame: Day 30

Number of patients with good biological efficiency of the antiplatelet therapy assessed by VerifyNow (VN)

Time frame: Day 30

Number of patients with new cerebral event assessed by brain Magnetic Resonance Imaging (MRI)

Time frame: Day 5

Number of high-intensity transient signals (HITS) assessed by transcranial Doppler

Time frame: Day 1

Assessment of neurological status by the score of Mini Mental State Examination (MMSE)