Back to results

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

Primary Purpose

Aortic Valve Stenosis

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Ticagrelor alone

Combination lysine acetylsalicylate - clopidogrel

About this trial

This is an interventional prevention trial for Aortic Valve Stenosis focused on measuring TAVI, Antiplatelet agent, Ticagrelor, Cerebrovascular events

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

CHRU de Lille
APHM
CHRU de Nîmes
APHP
CHU de Bordeaux

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard group

Ticagrelor group

Arm Description

154 patients

Outcomes

Primary Outcome Measures

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

Number of patient died

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

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

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

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

Number of patients presenting major vascular complications

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

Secondary Outcome Measures

Number of patients presenting at least one conduction disturbance or arrhythmias

Number of patients presenting at least one other TAVI related complication

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

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

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

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

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

Assessment of neurological status by the Dubois's 5 words test

Assessment of neurological status by the Geriatric Depression Scale (GDS)

Assessment of neurological status by the basic Activities of Daily Living (ADL) questionnaire

Assessment of neurological status by the Instrumental Activities of Daily Life (IADL) questionnaire

Assessment of neurological status by the Short Form Health Survey (SF-12) questionnaire

Full Information

NCT ID

NCT02817789

First Posted

April 29, 2016

Last Updated

February 8, 2022

Sponsor

University Hospital, Bordeaux

1. Study Identification

Unique Protocol Identification Number

NCT02817789

Brief Title

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

Acronym

TICTAVI

Study Type

Interventional

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Completed

Study Start Date

May 9, 2016 (Actual)

Primary Completion Date

May 30, 2018 (Actual)

Study Completion Date

May 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Bordeaux

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aortic Valve Stenosis

Keywords

TAVI, Antiplatelet agent, Ticagrelor, Cerebrovascular events

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Standard group

Arm Type

Active Comparator

Arm Description

154 patients

Arm Title

Ticagrelor group

Arm Type

Experimental

Arm Description

154 patients

Intervention Type

Drug

Intervention Name(s)

Ticagrelor alone

Intervention Description

180 mg loading dose before intervention and 90 mg twice daily during 30 days after the procedure

Intervention Type

Drug

Intervention Name(s)

Combination lysine acetylsalicylate - clopidogrel

Intervention Description

75 mg before and 75 mg daily after the procedure of lysine acetylsalicylate and 300mg loading dose before and 75 mg of clopidogrel daily after the procedure

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Day 30

Title

Number of patient died

Time Frame

Day 30

Title

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

Description

Time Frame

Day 30

Title

Number of patient presenting life-threatening bleeding

Description

Time Frame

Day 30

Title

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

Time Frame

Day 30

Title

Time Frame

Day 30

Title

Number of patients presenting major vascular complications

Time Frame

Day 30

Title

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 Outcome Measure Information:

Title

Number of patients presenting at least one conduction disturbance or arrhythmias

Time Frame

Day 30

Title

Number of patients presenting at least one other TAVI related complication

Time Frame

Day 30

Title

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

Time Frame

Day 30

Title

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

Time Frame

Day 30

Title

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

Time Frame

Day 5

Title

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

Time Frame

Day 1

Title

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

Time Frame

At baseline and day 30

Title

Assessment of neurological status by the Dubois's 5 words test

Time Frame

At baseline and day 30

Title

Assessment of neurological status by the Geriatric Depression Scale (GDS)

Time Frame

At baseline and day 30

Title

Assessment of neurological status by the basic Activities of Daily Living (ADL) questionnaire

Time Frame

At baseline and day 30

Title

Assessment of neurological status by the Instrumental Activities of Daily Life (IADL) questionnaire

Time Frame

At baseline and day 30

Title

Assessment of neurological status by the Short Form Health Survey (SF-12) questionnaire

Time Frame

At baseline and day 30

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lionel LEROUX, Dr

Organizational Affiliation

University Hospital, Bordeaux

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHRU de Lille

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

APHM

City

Marseille

ZIP/Postal Code

13005

Country

France

Facility Name

CHRU de Nîmes

City

Nîmes

ZIP/Postal Code

30029

Country

France

Facility Name

APHP

City

Paris

ZIP/Postal Code

75013

Country

France

Facility Name

CHU de Bordeaux

City

Pessac

ZIP/Postal Code

33604

Country

France

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs