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

NCT02817789 | Completed Phase 3 DMC

• 1 other identifier: CHUBX 2014/24
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

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.

Conditions

Aortic Valve Stenosis

Keywords

TAVI; Antiplatelet agent; Ticagrelor; Cerebrovascular events

Outcome Measures

Primary Outcomes (8)

• 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

  Day 30

• Number of patient died

  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

  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

  Day 30

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

  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

  Day 30

• Number of patients presenting major vascular complications

  Day 30

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

  Day 30

Secondary Outcomes (12)

• Number of patients presenting at least one conduction disturbance or arrhythmias

  Day 30

• Number of patients presenting at least one other TAVI related complication

  Day 30

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

  Day 30

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

  Day 30

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

  Day 5

Study Arms (2)

Standard group

ACTIVE COMPARATOR

154 patients

Drug: Combination lysine acetylsalicylate - clopidogrel

Ticagrelor group

EXPERIMENTAL

154 patients

Drug: Ticagrelor alone

Interventions

Ticagrelor alone DRUG

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

Ticagrelor group

Combination lysine acetylsalicylate - clopidogrel DRUG

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

Standard group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (5)

CHRU de Lille

Lille, 59037, France

Location

APHM

Marseille, 13005, France

Location

CHRU de Nîmes

Nîmes, 30029, France

Location

APHP

Paris, 75013, France

Location

CHU de Bordeaux

Pessac, 33604, France

Location

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Lionel LEROUX, Dr

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2016
• First Posted: June 29, 2016
• Study Start: May 9, 2016
• Primary Completion: May 30, 2018
• Study Completion: May 30, 2018
• Last Updated: February 14, 2022

Record last verified: 2022-02

Locations

FR (5)