Aspirin Versus Aspirin+Clopidogrel as Antithrombotic Treatment Following TAVI

Stroke Clinical Trial

— ARTE  

Official title:

Aspirin Versus Aspirin + ClopidogRel as Antithrombotic Treatment Following Transcatheter Aortic Valve Implantation With the Edwards Valve. A Randomized Study (the ARTE Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02640794
• Other study ID #: ARTE2
• Status: Completed
• Phase: Phase 4
• Start date: January 2015
• Est. completion date: March 2018

Study information

• Verified date: July 2018
• Source: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare aspirin/acetylsalicylic acid+ clopidogrel with aspirin/acetylsalicylic acid alone as antithrombotic treatment following TAVI for the prevention of major ischemic events (MI, ischemic stroke) or death without increasing the risk of major bleeding events.

Description:

Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to standard aortic valve replacement for the treatment of patients considered to be at very high or prohibitive surgical risk. Nowadays the procedure is associated with a very high success rate (>95%) but major peri-procedural ischemic complications such as myocardial infarction (MI) or ischemic stroke occur in about 2% (0% to 17%) and 3% (2% to 7%) of the cases, respectively. The recently published PARTNER trial showed a stroke rate as high as 6.5% within the 30 days following TAVI, with most (77%) of these events diagnosed as major strokes. In order to avoid such ischemic complications full dose anticoagulation (usually intravenous heparin) is administered during the TAVI procedure, whereas aspirin (long-term) + clopidogrel (1 to 6 months) have been the recommended antithrombotic treatment following the procedure. However, this antithrombotic regime has been recommended on an empirical basis, and no studies have as yet shown the efficacy of aspirin + clopidogrel vs. aspirin alone or no antithrombotic treatment in preventing ischemic events following TAVI procedures. Also, patients undergoing TAVI nowadays are usually octogenarians and very frequently exhibit comorbidities such as hypertension, abnormal renal function or prior cerebrovascular disease, which significantly increase the risk of major bleeding. Indeed, TAVI procedures can also be associated with major vascular complications which in turn can complicate with life-threatening or major bleeding. It is well know that clopidogrel on top of aspirin is associated with a higher rate of major bleeding complications, especially in elderly patients. It would therefore be of major clinical relevance to determine the risk/benefit ratio of using a dual antithrombotic therapy following TAVI procedures in order to recommend the most appropriate antithrombotic treatment in this high-risk population. The ARTE trial is a multicenter randomized study to evaluate the efficacy and safety of aspirin/acetylsalicylic acid versus aspirin/acetylsalicylic acid+ clopidogrel as antithrombotic treatment after TAVI.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 222
• Est. completion date: March 2018
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients undergoing a TAVI procedure with the Edwards valve.

Exclusion Criteria:

• Need for chronic anticoagulation treatment

• Major bleeding within the 3 months prior to the TAVI procedure

• Prior intracranial bleeding

• Drug-eluting stent implantation within the year prior to the TAVI procedure

• Allergy to clopidogrel and/or aspirin/acetylsalicylic acid

Related Conditions & MeSH terms

• Aortic Valve Disease
• Bleeding
• Hemorrhage
• Infarction
• Myocardial Infarction
• Stroke

Intervention

Drug:
• Clopidogrel
Clopidogrel therapy will start within 24 hrs before the TAVI procedure in cases where a transfemoral approach is used and within 24 hrs after the TAVI procedure in cases where a transapical approach is used. The initial dose of clopidogrel will be of 300 mg followed by 75 mg/die. The duration of clopidogrel treatment will be of 3 months.
• Aspirin
Aspirin/acetylsalicylic acid (80-325 mg/d). Aspirin/acetylsalicylic acid therapy will start at least 24 hrs before the TAVI procedure and continued for at least 6 months.

Locations

Country	Name	City	State
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Quebec	Quebec
Canada	St Michael's Hospital	Toronto	Ontario
Chile	Hospital San Borja Arriaran	Santiago
Spain	Hospital Vall d'Hebron de Barcelona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Countries where clinical trial is conducted

Canada,  Chile,  Spain, 

References & Publications (11)

ACTIVE Investigators, Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, Yusuf S. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med. 2009 May 14;360(20):2066-78. doi: 10.1056/NEJMoa0901301. Epub — View Citation

Delaney JA, Opatrny L, Brophy JM, Suissa S. Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007 Aug 14;177(4):347-51. — View Citation

Gurvitch R, Wood DA, Tay EL, Leipsic J, Ye J, Lichtenstein SV, Thompson CR, Carere RG, Wijesinghe N, Nietlispach F, Boone RH, Lauck S, Cheung A, Webb JG. Transcatheter aortic valve implantation: durability of clinical and hemodynamic outcomes beyond 3 yea — View Citation

Hansen ML, Sørensen R, Clausen MT, Fog-Petersen ML, Raunsø J, Gadsbøll N, Gislason GH, Folke F, Andersen SS, Schramm TK, Abildstrøm SZ, Poulsen HE, Køber L, Torp-Pedersen C. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and — View Citation

Leon MB, Piazza N, Nikolsky E, Blackstone EH, Cutlip DE, Kappetein AP, Krucoff MW, Mack M, Mehran R, Miller C, Morel MA, Petersen J, Popma JJ, Takkenberg JJ, Vahanian A, van Es GA, Vranckx P, Webb JG, Windecker S, Serruys PW. Standardized endpoint definit — View Citation

Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S; PARTNER Trial Inves — View Citation

Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010 — View Citation

Rodés-Cabau J, Webb JG, Cheung A, Ye J, Dumont E, Feindel CM, Osten M, Natarajan MK, Velianou JL, Martucci G, DeVarennes B, Chisholm R, Peterson MD, Lichtenstein SV, Nietlispach F, Doyle D, DeLarochellière R, Teoh K, Chu V, Dancea A, Lachapelle K, Cheema — View Citation

Rodés-Cabau J. [Progress in transcatheter aortic valve implantation]. Rev Esp Cardiol. 2010 Apr;63(4):439-50. Review. Spanish. — View Citation

Shehab N, Sperling LS, Kegler SR, Budnitz DS. National estimates of emergency department visits for hemorrhage-related adverse events from clopidogrel plus aspirin and from warfarin. Arch Intern Med. 2010 Nov 22;170(21):1926-33. doi: 10.1001/archinternmed — View Citation

Thomas M, Schymik G, Walther T, Himbert D, Lefèvre T, Treede H, Eggebrecht H, Rubino P, Michev I, Lange R, Anderson WN, Wendler O. Thirty-day results of the SAPIEN aortic Bioprosthesis European Outcome (SOURCE) Registry: A European registry of transcathet — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of death, MI, ischemic stroke/Transient ischemic attack (TIA) or life threatening/major bleeding at 3-month follow-up.	The composite endpoint of incidence of death, MI, ischemic stroke/Transient ischemic attack (TIA) or life life threatening/major bleeding at 3-month follow-up will be analyzed	3-month follow-up
Secondary	Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at 30 days	The composite endpoint of Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at 30 days will be analyzed	30 days
Secondary	Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at at 12-month follow-up	The composite endpoint of Incidence of death, MI, ischemic stroke/TIA or life threatening/major bleeding at at 12-month follow-up will be analyzed.	12-month follow-up
Secondary	Incidence of MI or ischemic stroke at 30 days and at 12-month follow-up	The composite endpoint of incidence of MI or ischemic stroke at 30 days and at 12-month follow-up will be analyzed	12-month follow-up
Secondary	Cardiovascular death at 30 days and at 12-month follow-up	The incidence of cardiovascular death at 30 days and at 12-month follow-up will be analyzed	30 days and at 12-month follow-up
Secondary	Cost-effectiveness of clopidogrel on top of aspirin/acetylsalicylic acid following TAVI	Cost-effectiveness of clopidogrel on top of aspirin/acetylsalicylic acid following TAVI will be analyzed	30 days and at 12-month follow-up
Secondary	Rate of minor bleeding at 30 days and at 12-month follow-up	Rate of minor bleeding at 30 days and at 12-month follow-up will be analyzed	30 days and at 12-month follow-up