Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation

Phase 4

Completed

• Conditions: Aortic Valve Disease; Stroke; Myocardial Infarction; Bleeding
• Interventions: Drug: Aspirin + clopidogrel; Drug: OAC monotherapy; Drug: Aspirin monotherapy; Drug: OAC + clopicogrel

• Registration Number: NCT02247128
• Lead Sponsor: St. Antonius Hospital

Brief Summary

At present, a variety of antithrombotic regimens are prescribed in the early postprocedure period after transcatheter aortic valve implantation (TAVI). Dual antiplatelet therapy (DAPT) using aspirin and a thienopyridine in the initial period after TAVI is the recommended strategy; however, mono antiplatelet therapy using aspirin is suggested not to be inferior. In patients with atrial fibrillation (AF) or another indication for oral anticoagulation (OAC), no recommendations on best treatment regimen currently exist although triple therapy (OAC + DAPT) is best avoided due to increased bleeding risk.

We hypothesise that the omission of clopidogrel in the first 3 months after TAVI is safer and not less beneficial than the addition of clopidogrel to aspirin (cohort A) or OAC (cohort B).

Detailed Description

The trial consists of two cohorts:

* Cohort A, patients without an indication for OAC prior to TAVI.

* Cohort B, patients with an indication for OAC prior to TAVI (eg. atrial fibrillation, mechanic mitral valve prosthesis).

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2014-09-19
• Study First Submitted QC: 2014-09-19
• Study First Posted: 2014-09-23
• Primary Completion: 2020-03
• Status Verified: 2020-04
• Study Completion: 2020-04
• Last Update Submitted: 2020-04-29
• Last Update Posted: 2020-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1016

Inclusion Criteria

• Cohort A

  1. Patient has provided written informed consent.

• Cohort B

  1. Need for long-term oral anticoagulation;
  2. Patient has provided written informed consent.

Exclusion Criteria

• Cohort A

  1. Need for long-term oral anticoagulation;
  2. Drug-eluting stent implantation within 3 months prior to TAVI procedure;
  3. Bare-metal stent implantation within 1 month prior to TAVI procedure;
  4. Allergy or intolerance to aspirin or clopidogrel.

• Cohort B

  1. Drug-eluting stent implantation within 3 months prior to TAVI procedure;
  2. Bare-metal stent implantation within 1 month prior to TAVI procedure;
  3. Allergy or intolerance to (N)OAC or clopidogrel.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aspirin + Clopicogrel (Cohort A)	Aspirin + clopidogrel	Cohort A: patients will receive clopidogrel (75mg quaque die (qD), 3 months) on top of low-dose aspirin (≤100mg qD, at least 1 year but recommended lifelong). When a patient in Cohort A doesn't already takes aspirin, a loading dose of 300mg will be given within 24 hours prior to TAVI. The loading dose for clopidogrel is 300mg, and will be given within 24 hours prior to TAVI.
OAC monotherapy (Cohort B)	OAC monotherapy	Cohort B: patients will receive OAC according to its indication. It is recommended to continue the OAC therapy peri-procedural (International Normalized Ratio aimed at 2.0). It is recommended to omit antiplatelet therapy (e.g. clopidogrel) at least 5 days prior to the TAVI procedure.
Aspirin monotherapy (Cohort A)	Aspirin monotherapy	Cohort A: patients will receive low-dose aspirin (≤100mg qD, at least 1 year but recommended lifelong). When a patients doesn't already takes aspirin, a loading dose of 300mg will be given within 24 hours prior to TAVI. It is recommended to omit other antiplatelet therapy (e.g. clopidogrel) at least 5 days prior to the TAVI procedure.
OAC + Clopicogrel (Cohort B)	OAC + clopicogrel	Cohort B: patients will receive clopidogrel (75mg qD, 3 months) on top of OAC (according to its indication). The loading dose for clopidogrel is 300mg, and will be given within 24 hours prior to TAVI. It is recommended to omit other antiplatelet therapy (e.g. aspirin) at least 5 days prior to the TAVI procedure.

Primary Outcome Measures

Name	Time	Method
Safety endpoint	1 year	The primary outcome is a safety endpoint, defined as freedom of all bleeding complications at 1 year after TAVI. The co-primary outcome is the safety endpoint defined as freedom of non-procedure related bleeding complications at 1 year after TAVI. For the classification of bleeding complications the Bleeding Academic Research Consortium Definition for Bleeding (BARC) bleeding classification is primarily used according to the Valve Academic Research Consortium (VARC).

Secondary Outcome Measures

Name	Time	Method
Net-clinical benefit endpoint	1 year	The secondary outcome is a net-clinical benefit endpoint, defined as freedom of the non-hierarchical composite of cardiovascular mortality, non-procedure related bleeding, stroke, or myocardial infarction at 1 year after TAVI.
Efficacy endpoint	1 year	The co-secondary outcome is an efficacy endpoint, defined as freedom of the non-hierarchical composite of cardiovascular mortality, ischemic stroke, or myocardial infarction at 1 year after TAVI.

Trial Locations

Locations (17)

Academic Medical Centre (AMC); 🇳🇱 Amsterdam, Noord Holland, Netherlands

Algemeen Stedelijk Ziekenhuis; 🇧🇪 Aalst, Belgium

Imelda Ziekenhuis; 🇧🇪 Bonheiden, Belgium

Medisch Spectrum Twente; 🇳🇱 Enschede, Netherlands

Academic Hospital; 🇳🇱 Maastricht, Netherlands

Onze Lieve Vrouwe Ziekenhuis; 🇧🇪 Aalst, Belgium

Haga Ziekenhuis; 🇳🇱 Den Haag, Netherlands

Universitair Medisch Centrum Leiden; 🇳🇱 Leiden, Netherlands

University Medical Center; 🇳🇱 Groningen, Netherlands

Algemeen Ziekenhuis Sint Jan; 🇧🇪 Brugge, Belgium

Charles university, Third Faculty of Medicine; 🇨🇿 Prague, Czechia

National Institute Surgery Cardiaque Et De Cardiologie Interventionnelle; 🇱🇺 Luxembourg, Luxembourg

Isala Clinics; 🇳🇱 Zwolle, Overijssel, Netherlands

Ziekenhuis Oost-Limburg; 🇧🇪 Genk, Belgium

Universitair Ziekenhuis Leuven; 🇧🇪 Leuven, Belgium

St. Antonius Hospital; 🇳🇱 Nieuwegein, Utrecht, Netherlands

University Medical Center Utrecht (UMCU); 🇳🇱 Utrecht, Netherlands