Study comparing the action of drugs : ticagrelor, clopidogrel combined with acetylsalicylic acid in preventing ischemic strokes during transcatheter aortic valve implantation operations.
- Conditions
- Preventing cerebrovascular embolic events during the TAVI procedureMedDRA version: 19.0Level: PTClassification code 10002918Term: Aortic valve stenosisSystem Organ Class: 10007541 - Cardiac disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2015-005630-21-GR
- Lead Sponsor
- ational and Kapodistrian University of Athens
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
Subjects eligible for study inclusion must meet all of the following criteria:
1.The subject (or where unable to do so, their legally acceptable representative) must be able to provide written informed consent prior to any study specific criteria, stating that he or she understands the purpose of and the procedures required for the study and is willing to participate in the study.
2.Female and/or male subjects aged 18 years or older.
3.High risk (EuroSCORE =18, or considered inoperable) for surgical aortic valve replacement.
4.Is expected to benefit from the placement of TAVI.
5.Does not suffer from any disease or condition that would limit his/her life expectancy of <6 months.
6.The subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
7.Subjects must meet the following laboratory results from Visit 0 for study inclusion :
a. Hemoglobin = 10 g/dL
b. Platelets = 100 X 103 cells/µL
c. Absolute neutrophil count (ANC) = 1000 cells/µL
d. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels must be within 1.5 times the upper limit of normal (ULN) range for the laboratory conducting the test.
e. Total bilirubin = 2x ULN.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Subjects will not enter the study if any of the following exclusion criteria are fulfilled:
1.Have scheduled any elective surgery in the next 4 months following screening procedures.
2.History of hypocoagulopathies.
3.Previous thromboembolism or known hypercoagulopathy (acquired or congenital).
4.Antiplatelet therapy, other than ASA, within 7 days before randomization that cannot be discontinued due to the underlying disease.
5.History of gastric or duodenal ulcer disease verified by endoscopy or barium meal double-contrast technique within the 3 months.
6.Moderate or severe hepatic impairment.
7.Known hypersensitivity to any of the investigational products or their components.
8.Presence of any other clinically significant disease or disorder which, in the opinion of the Investigator (by its nature or by being inadequately controlled), might put the subject at risk due to participation in the study, or may influence the conduct or the interpretation of the results of the study or the subject’s ability to complete the study.
9.Any identified contraindication for using Ticagrelor, Clopidogrel or ASA.
10.History or recent findings of atrial fibrillation.
11.Significant carotid artery disease on either internal carotid artery, as defined by a >50 % diameter reduction on carotid ultrasonography.
12.Unwillingness to receive or intolerant to any blood products.
13.Previous trauma or surgery to either femoral vein.
14.Major surgical procedure or trauma within the 30 days prior to enrolment.
15.Mechanical heart valve (any location).
16.Mitral or aortic bioprosthetic valve.
17.The subject is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
18.Reproductive status:
a.Women who are pregnant or planning a pregnancy within 1 month of the end of study;
b.Women who are breastfeeding;
c.Women of childbearing potential who are unwilling or unable to use two highly effective methods of birth control to avoid pregnancy for the entire study period, as evaluated by the Investigator. Women who are not of childbearing potential are those that have a history of hysterectomy, bilateral oophorectomy, or are postmenopausal with no history of menstrual flow for = 12 months prior to the screening Visit.
19.International normalized ratio (INR) = 2 on the day before the TAVI procedure.
20.History of hemorrhagic stroke, intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular hemorrhage, intracerebral mass or aneurysm, or arteriovenous malformation.
21.Severe left ventricular dysfunction (left ventricular ejection fraction<15%).
22.Severe aortic regurgitation or mitral regurgitation, according to the 2012 European Society of Cardiology and the European Association for Cardio-Thoracic Surgery guidelines (See Appendix 2)
23.Hemodynamic instability (e.g. requiring inotropic or intra-aortic balloon pump support) within 2 hours of the procedure.
24.Subject is dialysis dependent.
25.Any condition requiring the use of anticoagulants that cannot be stopped for the duration of the study.
26.Acute myocardial infarction, major surgery or any therapeutic cardiac procedure (other than balloon aortic valvuloplasty) within 30 days.
27.Gastrointestinal or genitourinary bleed within 30 days.
28.Absolute contraindications or allergy to iodinated co
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To identify any potential differences between the two treatment groups, subjects receiving Ticagrelor with ASA vs. those receiving Clopidogrel with ASA, in preventing cerebrovascular embolic events during the TAVI procedure, as assessed by measuring the number of HITS with an operative transcranial continuous-function Doppler.;Secondary Objective: •To assess the safety of Ticagrelor by assessment of all AEs, physical examination and vital signs.<br>•To evaluate the differences between the two treatment groups, in the incidence in bleeding events of each of the three grades, as defined by VARC-2, perioperatively and at 90 days.<br>;Primary end point(s): The primary endpoint of this study is the number of confirmed HITS, as assessed by TCD, between the two treatment groups during the TAVI procedure.;Timepoint(s) of evaluation of this end point: Day 0
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The differences in the incidence of cerebral embolic events between the two treatment groups, as assessed by HITS measured by TCD at subject discharge. Days 4-7<br><br><br>The differences in the incidence of cerebral embolic events in each treatment group, as assessed by HITS measured by TCD preoperatively, during the TAVI procedure, and at subject discharge. Days -10 to -1, Day 0, Days 4-7<br><br>The differences between the two treatment groups in induced platelet inhibition, as assessed by the use of the P2Y12 VerifyNow® assay at the day of the procedure. Day 0<br><br>The differences between the two treatment groups in induced platelet inhibition, as assessed by the use of the P2Y12 VerifyNow® assay at subject discharge. Days 4-7;Timepoint(s) of evaluation of this end point: See E.5.2<br>