Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation (POPular-TAVI)

• ClinicalTrials.gov Identifier: NCT02247128
• Recruitment Status: Active, not recruiting
• First Posted: September 23, 2014
• Last Update Posted: March 21, 2019
• Sponsor: St. Antonius Hospital
• Information provided by (Responsible Party): J.M. ten Berg, St. Antonius Hospital

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Aortic Valve Disease; Myocardial Infarction; Stroke; Bleeding	Drug: Aspirin + clopidogrel; Drug: Aspirin monotherapy; Drug: OAC + clopicogrel; Drug: OAC monotherapy	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1000 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Antiplatelet Therapy for Patients Undergoing Transcatheter Aortic Valve Implantation
• Study Start Date: January 2014
• Estimated Primary Completion Date: March 2020
• Estimated Study Completion Date: March 2020

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Aspirin + Clopicogrel (Cohort A); 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
Active Comparator: Aspirin monotherapy (Cohort A); 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
Active Comparator: OAC + Clopicogrel (Cohort B); 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
Active Comparator: OAC monotherapy (Cohort B); 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

Outcome Measures

Primary Outcome Measures :

1. Safety endpoint [ Time Frame: 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 :

1. Net-clinical benefit endpoint [ Time Frame: 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.
2. Efficacy endpoint [ Time Frame: 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.

Other Outcome Measures:

1. Pharmacoeconomics endpoint [ Time Frame: 1 year ]
   Outcome measure is quality-adjusted life years

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Belgium

Algemeen Stedelijk Ziekenhuis

Aalst, Belgium

Onze Lieve Vrouwe Ziekenhuis

Aalst, Belgium

Imelda Ziekenhuis

Bonheiden, Belgium

Algemeen Ziekenhuis Sint Jan

Brugge, Belgium

Ziekenhuis Oost-Limburg

Genk, Belgium

Universitair Ziekenhuis Leuven

Leuven, Belgium

Czechia

Charles university, Third Faculty of Medicine

Prague, Czechia

Luxembourg

National Institute Surgery Cardiaque Et De Cardiologie Interventionnelle

Luxembourg, Luxembourg

Netherlands

Academic Medical Centre (AMC)

Amsterdam, Noord Holland, Netherlands, 1105 AZ

Isala Clinics

Zwolle, Overijssel, Netherlands, 8011 JW

St. Antonius Hospital

Nieuwegein, Utrecht, Netherlands, 3435CM

Haga Ziekenhuis

Den Haag, Netherlands

Medisch Spectrum Twente

Enschede, Netherlands

University Medical Center

Groningen, Netherlands, 9700 RB

Universitair Medisch Centrum Leiden

Leiden, Netherlands

Academic Hospital

Maastricht, Netherlands, 6229 HX

University Medical Center Utrecht (UMCU)

Utrecht, Netherlands, 3584 CX

Sponsors and Collaborators

St. Antonius Hospital

Investigators

• Principal Investigator: Jurrien M ten Berg, PhD, MD; St. Antonius Hospital
• Principal Investigator: Pieter R Stella, MD, PhD; University Medical Center Utrecht (UMCU)

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: J.M. ten Berg, Prof. Dr., St. Antonius Hospital
• ClinicalTrials.gov Identifier: NCT02247128
• Other Study ID Numbers: POPTAV006
• First Posted: September 23, 2014
• Last Update Posted: March 21, 2019
• Last Verified: March 2019

Keywords provided by J.M. ten Berg, St. Antonius Hospital:

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)

Additional relevant MeSH terms:

Myocardial Infarction; Infarction; Hemorrhage; Vascular Diseases; Cardiovascular Diseases; Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Aspirin; Clopidogrel; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists