Study of Platelet Activation by Severe Aortic Stenosis and Its Correction by Transcatheter Aortic Valve Implantation

NCT ID: NCT02504632

Last Updated: 2017-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2015-10-31

Brief Summary

Study of platelet activation by severe aortic stenosis and its correction by Transcatheter Aortic Valve Implantation (TAVI)

Detailed Description

• Background: TAVI has emerged as an alternative to surgical aortic valve replacement for patients with severe, symptomatic aortic stenosis (AS) and is expanding worldwide with more than 50,000 patients treated to date.
• Purpose Changes in haemostasis, particularly in platelet activation or reactivity before, during and after TAVI have never been studied. Valve replacement is known to alleviate von Willebrand factor abnormalities associated with AS. A potential improvement of platelet function could also occur after TAVI. Indeed, circulating platelets may be desensitized and under-reactive due to multiple passages through the stenotic valve and could recover normal reactivity after TAVI. Besides, TAVI presents a risk of major ischemic complications. The investigators can hypothesize the involvement of high reactive platelets in peri-procedural thrombotic or ischemic events. This study of the platelet activation kinetics will be performed by comparing several specific markers before and at various times after valve implantation.
• Primary outcome To evaluate the kinetics of platelet activation before and at various times after valve implantation, by comparing several specific markers in peripheral venous blood samples before (day 0) and at days 1 and 5±1 after the procedure.
• Study design and number of subjects: This is a prospective, monocentric, study. The test group includes up to 15 patients treated by transfemoral TAVI using a MedTronic CoreValve (MCV) prosthesis. Platelet activation will be studied before and after the procedure and compared to a reference established with an age-matched, aspirin-treated, atherosclerotic population (30 patients in the control group).
• Eligibility criteria:

• inclusion criteria: test group: patients with severe aortic stenosis and transfemoral TAVI with MCV aspirin treatment . Control group: age-matched patients with stable coronary artery disease treated by aspirin but without aortic stenosis.
• exclusion criteria: recent (1 month) acute coronary syndrome; treatment by anti platelet agents other than aspirin
• Procedures: Specific platelet activation markers, circulating platelet/monocytes aggregates, platelet reactivity and vWF will be assessed in peripheral venous blood before, 1 and 5 days after TAVI and in ascending aorta during the procedure.

Conditions

Aortic Stenosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

test group

Patient with severe, symptomatic AS (Aortic valve area \< 0,6 cm2/m2 SC), deemed, after multidisciplinary heart team evaluation, contra-indicated or at high risk for surgery and suitable for TF TAVI with a MCV prosthesis.

Group Type: EXPERIMENTAL

test

Intervention Type: OTHER

Peripheral venous citrated blood will be collected just before and 10-15 min after the implantation of the valve. Samples will be obtained after starting the infusion of contrast media. In peripheral venous blood before 24 h and after the procedure and at hospital discharge, 4-6 days when the usual transient thrombocytopenia after TAVI has recovered.

The results will be used to analyse the kinetics of haematological changes in peripheral blood following aortic valve replacement.

Platelet activation will be monitored by flow cytometry to assess the expression of specific membrane markers and the phosphorylation of signalling proteins, as well as the formation of platelet/monocyte aggregates.

control group

Patient with stable coronary artery disease, unscathed of AS Patient under aspirin treatment (75-160 mg/d for at least one week)

Group Type: OTHER

control group

Intervention Type: OTHER

In this group, only one sample (2 tubes filled with 4.5 ml, i.e. 9ml) will be obtained in venous peripheral blood to establish reference values in age-matched, aspirin-treated, atherosclerotic population.

Interventions

test

Peripheral venous citrated blood will be collected just before and 10-15 min after the implantation of the valve. Samples will be obtained after starting the infusion of contrast media. In peripheral venous blood before 24 h and after the procedure and at hospital discharge, 4-6 days when the usual transient thrombocytopenia after TAVI has recovered.

The results will be used to analyse the kinetics of haematological changes in peripheral blood following aortic valve replacement.

Platelet activation will be monitored by flow cytometry to assess the expression of specific membrane markers and the phosphorylation of signalling proteins, as well as the formation of platelet/monocyte aggregates.

Intervention Type: OTHER

control group

In this group, only one sample (2 tubes filled with 4.5 ml, i.e. 9ml) will be obtained in venous peripheral blood to establish reference values in age-matched, aspirin-treated, atherosclerotic population.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Test group

• Severe symptomatic AS (Aortic valve area < 0,6 cm2/m2 SC), deemed, after multidisciplinary heart team evaluation, contra-indicated or at high risk for surgery and suitable for TF TAVI with a MCV prosthesis.
• Aspirin treatment (75-160 mg/d for at least one week)
• Control group

• Stable coronary artery disease, unscathed of AS
• Aspirin treatment (75-160 mg/d for at least one week)

Exclusion Criteria

• Test group:

• Acute coronary syndrome 1 month before inclusion
• Any co-morbidity limiting life-expectancy < 1 year
• Terminal chronic kidney disease requiring hemodialysis thrombocytopenia <100 G/L, anemia (Hb < 10 g/dl)
• Treatment by another antiplatelet agent within 10 days before the procedure
• Control group:

• Acute coronary syndrome 1 month before inclusion
• Any co-morbidity limiting life-expectancy < 1 year
• Terminal chronic kidney disease requiring hemodialysis
• Thrombocytopenia <100 G/L
• Treatment by another antiplatelet agent within 10 days before the procedure

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medtronic

INDUSTRY

Sponsor Role: collaborator

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pierre SIE, MD PhD

Role: STUDY_CHAIR

University Hospital, Toulouse

Locations

CHU TOULOUSE-Hôpital Rangueil

Toulouse, , France

Countries

France

Other Identifiers

14 7078 03

Identifier Type: -

Identifier Source: org_study_id