Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation

NCT02247128 | Completed Phase 4 DMC

• 1 other identifier: POPTAV006
• Study Type: interventional
• Target: 1,016
• Locations: 4 countries
• Sites: 17

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).

Conditions

Aortic Valve Disease; Myocardial Infarction; Stroke; Bleeding

Keywords

Transcatheter Aortic Valve Implantation (TAVI); Transcatheter Aortic Valve Replacement (TAVR); Aortic Valve Disease; Aortic Stenosis; Myocardial Infarction; Ischemic stroke; Bleeding; Thrombosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Aspirin; Clopidogrel; Prasugrel; Ticagrelor; Antithrombotic treatment; Oral anticoagulation; Warfarin; Platelet Aggregation Inhibitors; Genetic Testing; Cytochrome P450 2C19 (CYP2C19); Prostaglandin-endoperoxide synthase 2(PTGS2)

Outcome Measures

Primary Outcomes (1)

• Safety endpoint

  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).

  1 year

Secondary Outcomes (2)

• Net-clinical benefit endpoint

  1 year

• Efficacy endpoint

  1 year

Other Outcomes (1)

• Pharmacoeconomics endpoint

  1 year

Study Arms (4)

Aspirin + Clopicogrel (Cohort A)

ACTIVE COMPARATOR

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.

Drug: Aspirin + clopidogrel

Aspirin monotherapy (Cohort A)

ACTIVE COMPARATOR

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.

Drug: Aspirin monotherapy

OAC + Clopicogrel (Cohort B)

ACTIVE COMPARATOR

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.

Drug: OAC + clopicogrel

OAC monotherapy (Cohort B)

ACTIVE COMPARATOR

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.

Drug: OAC monotherapy

Interventions

Aspirin + clopidogrel DRUG

Aspirin + Clopicogrel (Cohort A)

Aspirin monotherapy DRUG

Aspirin monotherapy (Cohort A)

OAC + clopicogrel DRUG

OAC + Clopicogrel (Cohort B)

OAC monotherapy DRUG

OAC monotherapy (Cohort B)

Eligibility Criteria

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

You may qualify if:

• Cohort A
• \. Patient has provided written informed consent.
• Cohort B
• Need for long-term oral anticoagulation;
• Patient has provided written informed consent.

You may not qualify if:

• Cohort A
• Need for long-term oral anticoagulation;
• Drug-eluting stent implantation within 3 months prior to TAVI procedure;
• Bare-metal stent implantation within 1 month prior to TAVI procedure;
• Allergy or intolerance to aspirin or clopidogrel.
• Cohort B
• Drug-eluting stent implantation within 3 months prior to TAVI procedure;
• Bare-metal stent implantation within 1 month prior to TAVI procedure;
• Allergy or intolerance to (N)OAC or clopidogrel.

Sponsors & Collaborators

• St. Antonius Hospital: lead

Study Sites (17)

Algemeen Stedelijk Ziekenhuis

Aalst, Belgium

Location

Onze Lieve Vrouwe Ziekenhuis

Aalst, Belgium

Location

Imelda Ziekenhuis

Bonheiden, Belgium

Location

Algemeen Ziekenhuis Sint Jan

Bruges, Belgium

Location

Ziekenhuis Oost-Limburg

Genk, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, Belgium

Location

Charles university, Third Faculty of Medicine

Prague, Czechia

Location

National Institute Surgery Cardiaque Et De Cardiologie Interventionnelle

Luxembourg, Luxembourg

Location

Academic Medical Centre (AMC)

Amsterdam, North Holland, 1105 AZ, Netherlands

Location

Isala Clinics

Zwolle, Overijssel, 8011 JW, Netherlands

Location

St. Antonius Hospital

Nieuwegein, Utrecht, 3435CM, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

University Medical Center

Groningen, 9700 RB, Netherlands

Location

Universitair Medisch Centrum Leiden

Leiden, Netherlands

Location

Academic Hospital

Maastricht, 6229 HX, Netherlands

Location

Haga Ziekenhuis

The Hague, Netherlands

Location

University Medical Center Utrecht (UMCU)

Utrecht, 3584 CX, Netherlands

Location

Related Publications (3)

• Brouwer J, Nijenhuis VJ, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, Frambach P, De Bruyne B, van Houwelingen GK, Van Der Heyden JAS, Tousek P, van der Kley F, Buysschaert I, Schotborgh CE, Ferdinande B, van der Harst P, Roosen J, Peper J, Thielen FWF, Veenstra L, Chan Pin Yin DRPP, Swaans MJ, Rensing BJWM, van 't Hof AWJ, Timmers L, Kelder JC, Stella PR, Baan J, Ten Berg JM. Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med. 2020 Oct 8;383(15):1447-1457. doi: 10.1056/NEJMoa2017815. Epub 2020 Aug 30.

  PMID: 32865376 DERIVED

• Nijenhuis VJ, Brouwer J, Delewi R, Hermanides RS, Holvoet W, Dubois CLF, Frambach P, De Bruyne B, van Houwelingen GK, Van Der Heyden JAS, Tousek P, van der Kley F, Buysschaert I, Schotborgh CE, Ferdinande B, van der Harst P, Roosen J, Peper J, Thielen FWF, Veenstra L, Chan Pin Yin DRPP, Swaans MJ, Rensing BJWM, van 't Hof AWJ, Timmers L, Kelder JC, Stella PR, Baan J, Ten Berg JM. Anticoagulation with or without Clopidogrel after Transcatheter Aortic-Valve Implantation. N Engl J Med. 2020 Apr 30;382(18):1696-1707. doi: 10.1056/NEJMoa1915152. Epub 2020 Mar 29.

  PMID: 32223116 DERIVED

• Nijenhuis VJ, Bennaghmouch N, Hassell M, Baan J Jr, van Kuijk JP, Agostoni P, van 't Hof A, Kievit PC, Veenstra L, van der Harst P, van den Heuvel AF, den Heijer P, Kelder JC, Deneer VH, van der Kley F, Onorati F, Collet JP, Maisano F, Latib A, Huber K, Stella PR, Ten Berg JM. Rationale and design of POPular-TAVI: antiPlatelet therapy fOr Patients undergoing Transcatheter Aortic Valve Implantation. Am Heart J. 2016 Mar;173:77-85. doi: 10.1016/j.ahj.2015.11.008. Epub 2015 Dec 1.

  PMID: 26920599 DERIVED

MeSH Terms

Conditions

Aortic Valve Disease; Myocardial Infarction; Stroke; Hemorrhage; Aortic Valve Stenosis; Ischemic Stroke; Thrombosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis

Interventions

Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jurrien M ten Berg, PhD, MD

  St. Antonius Hospital

  PRINCIPAL INVESTIGATOR

• Pieter R Stella, MD, PhD

  University Medical Center Utrecht (UMCU)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: September 19, 2014
• First Posted: September 23, 2014
• Study Start: January 1, 2014
• Primary Completion: March 1, 2020
• Study Completion: April 1, 2020
• Last Updated: April 30, 2020

Record last verified: 2020-04

Locations

CZ (1); LU (1); BE (6); NL (9)