Clinical trial NCT02817789: Safety Profile Evaluation of TICagrelor Alone Compared to a Combination of Lysine Acetylsalicylate-Clopidogrel in the Context of Transcatheter Aortic Valve Implantation (TAVI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Aortic Valve Stenosis
Keywords: TAVI
Antiplatelet agent
Ticagrelor
Cerebrovascular events
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2016-06-29
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Number of patient presenting at least one event of the Valve Academic Research Consortium-2 (VARC2) composite endpoint
timeFrame: Day 30
measure: Number of patient died
timeFrame: Day 30
measure: Number of patient presenting stroke or Transient Ischemic Attack (TIA)
timeFrame: Day 30
measure: Number of patient presenting life-threatening bleeding
timeFrame: Day 30
measure: Number of patients presenting post-TAVI acute kidney failure stage 2 or 3 as assessed by VARC2
timeFrame: Day 30
measure: 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
timeFrame: Day 30
measure: Number of patients presenting major vascular complications
timeFrame: Day 30
measure: Number of patients requiring a new procedure like Balloon Aortic valvuloplasty (BAV), new procedure of TAVI or Surgical aortic valve replacement (SAVR)
timeFrame: Day 30
Secondary outcomes:
measure: Number of patients presenting at least one conduction disturbance or arrhythmias
timeFrame: Day 30
measure: Number of patients presenting at least one other TAVI related complication
timeFrame: Day 30
measure: Number of patients presenting at least one bleeding event (life-threatening, major or minor)
timeFrame: Day 30
measure: Number of patients with good biological efficiency of the antiplatelet therapy assessed by VerifyNow (VN)
timeFrame: Day 30
measure: Number of patients with new cerebral event assessed by brain Magnetic Resonance Imaging (MRI)
timeFrame: Day 5
measure: Number of high-intensity transient signals (HITS) assessed by transcranial Doppler
timeFrame: Day 1
measure: Assessment of neurological status by the score of Mini Mental State Examination (MMSE)
timeFrame: At baseline and day 30
measure: Assessment of neurological status by the Dubois's 5 words test
timeFrame: At baseline and day 30
measure: Assessment of neurological status by the Geriatric Depression Scale (GDS)
timeFrame: At baseline and day 30
measure: Assessment of neurological status by the basic Activities of Daily Living (ADL) questionnaire
timeFrame: At baseline and day 30
measure: Assessment of neurological status by the Instrumental Activities of Daily Life (IADL) questionnaire
timeFrame: At baseline and day 30
measure: Assessment of neurological status by the Short Form Health Survey (SF-12) questionnaire
timeFrame: At baseline and day 30
Other outcomes:
Locations:
city: Lille
country: France
facility: CHRU de Lille
city: Marseille
country: France
facility: APHM
city: Nîmes
country: France
facility: CHRU de Nîmes
city: Paris
country: France
facility: APHP
city: Pessac
country: France
facility: CHU de Bordeaux
Study officials:
affiliation: University Hospital, Bordeaux
name: Lionel LEROUX, Dr
role: PRINCIPAL_INVESTIGATOR
References: