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

Not Applicable

Completed

• Conditions: Aortic Stenosis
• Interventions: Other: test; Other: control group

• Registration Number: NCT02504632
• Lead Sponsor: University Hospital, Toulouse

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.

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2015-07-17
• Study First Submitted QC: 2015-07-20
• Study First Posted: 2015-07-22
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-12
• Last Update Posted: 2017-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
test group	test	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.
control group	control group	Patient with stable coronary artery disease, unscathed of AS Patient under aspirin treatment (75-160 mg/d for at least one week)

Primary Outcome Measures

Name	Time	Method
the change of kinetics of platelet activation	1 min before TAVI and 5±1 after TAVI	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 5±1 days after the procedure using flow cytometry (FACS).

Secondary Outcome Measures

Name	Time	Method
Changes of platelet activation	1 min before and 10 min after TAVI	platelet activation in aortic blood downstream of the stenotic valve before and 10 min after TAVI,
Changes of platelet activity	1 min before and day 5 after TAVI	platelet reactivity to selected agonists in peripheral venous blood samples before and at days 1 and 5±1,
changes in von Willebrand factor	1 min before and day 1 and 5 after TAVI	changes in von Willebrand factor in peripheral blood samples The activity and level of vWF antigen will be measured by immunotubidimetric methods

Trial Locations

Locations (1)

CHU TOULOUSE-Hôpital Rangueil; 🇫🇷 Toulouse, France