Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation (ISAR-TRIPLE)

• ClinicalTrials.gov Identifier: NCT00776633
• Recruitment Status: Unknown
• First Posted: October 21, 2008
• Last Update Posted: August 30, 2016
• Sponsor: Deutsches Herzzentrum Muenchen
• Information provided by (Responsible Party): Deutsches Herzzentrum Muenchen

Study Description

Brief Summary:

The investigators hypothesize that reducing the duration of clopidogrel therapy from 6 months to 6 weeks after DES implantation is associated with improved clinical outcomes in patients on ASA and an oral anticoagulant.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease; Atrial Fibrillation	Drug: aspirin; Drug: clopidogrel; Drug: oral anticoagulation	Phase 4

Detailed Description:

The introduction of drug-eluting stents (DES) was associated not only with a widening of the indication for percutaneous coronary intervention (PCI) but also with longer antithrombotic therapy duration. Dual antiplatelet therapy with ASA and a thienopyridine is very efficient in preventing adverse events after coronary stenting but it is inferior to oral anticoagulation (OAC) to reduce the risk of stroke in patients with atrial fibrillation. OAC is also superior to antiplatelet therapy in patients with mechanical heart valves and the therapy of choice for the treatment of deep vein thrombosis and pulmonary embolism. OAC is also administered for left ventricular thrombi and low ejection fraction. There is an increasing number of patients undergoing coronary stenting who are in need of life-long anticoagulation therapy and would therefore require a triple therapy consisting of aspirin, clopidogrel and oral anticoagulation. As oral anticoagulation and antithrombotic therapy impair primary and secondary hemostasis there are concerns that adding warfarin to dual antiplatelet therapy might cause increased bleeding rates. Several studies have retrospectively assessed efficacy and safety in patients receiving a triple therapy with various results: major bleeding rates varied from 3,1%-14,9% with total bleeding rates up to 27,5%. Prospective randomized data on this topic are not available. Therefore the aim of this study is to compare a 6 week versus a 6 month triple therapy after DES implantation.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 614 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intracoronary Stenting and Antithrombotic Regimen: Testing of a Six-week Versus a Six-month Clopidogrel Treatment Regimen in Patients With Concomitant Aspirin and Oral Anticoagulant Therapy Following Drug-eluting Stenting
• Study Start Date: September 2008
• Actual Primary Completion Date: December 2013
• Estimated Study Completion Date: September 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Short triple; 6 weeks triple therapy	Drug: aspirin; 6 weeks triple therapy with aspirin, clopidogrel and oral anticoagulation; Drug: clopidogrel; 6 months triple therapy with aspirin, clopidogrel and oral anticoagulation; Drug: oral anticoagulation
Active Comparator: Long triple; 6 months triple therapy	Drug: aspirin; 6 weeks triple therapy with aspirin, clopidogrel and oral anticoagulation; Drug: clopidogrel; 6 months triple therapy with aspirin, clopidogrel and oral anticoagulation; Drug: oral anticoagulation

Outcome Measures

Primary Outcome Measures :

1. Composite of death, myocardial infarction, definite stent thrombosis, stroke or major bleeding. [ Time Frame: 9 months ]

Secondary Outcome Measures :

1. Ischemic complications (composite of cardiac death, myocardial infarction, stent thrombosis or ischemic stroke) [ Time Frame: 9 months ]
2. Bleeding complications (Major bleeding) [ Time Frame: 9 months ]

Eligibility Criteria

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

Criteria

Key Inclusion Criteria:

1. Patients with an indication for oral anticoagulation and a DES implantation.
2. Informed, written consent by the patient or her/his legally-authorized representative for participation in the study.

Key Exclusion Criteria:

1. Age ≤18 years
2. Previous stent thrombosis
3. DES in left main

Contacts and Locations

Locations

Denmark

Aarhus University Hospital

Aarhus, Denmark, 8200

Germany

Deutsches Herzzentrum München

Munich, Germany, 80636

1. Medizinische Klinik, Klinikum rechts der Isar

München, Germany, 81675

Sponsors and Collaborators

Deutsches Herzzentrum Muenchen

Investigators

• Study Chair: Adnan Kastrati, MD; Deutsches Herzzentum München
• Principal Investigator: Stefanie Schulz, MD; Deutsches Herzzentrum Muenchen

More Information

Publications:

Rubboli A, Halperin JL, Airaksinen KE, Buerke M, Eeckhout E, Freedman SB, Gershlick AH, Schlitt A, Tse HF, Verheugt FW, Lip GY. Antithrombotic therapy in patients treated with oral anticoagulation undergoing coronary artery stenting. An expert consensus document with focus on atrial fibrillation. Ann Med. 2008;40(6):428-36. doi: 10.1080/07853890802089786.

Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, Richardt G, Alt E, Schmitt C, Ulm K. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996 Apr 25;334(17):1084-9. doi: 10.1056/NEJM199604253341702.

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

Fiedler KA, Maeng M, Mehilli J, Schulz-Schupke S, Byrne RA, Sibbing D, Hoppmann P, Schneider S, Fusaro M, Ott I, Kristensen SD, Ibrahim T, Massberg S, Schunkert H, Laugwitz KL, Kastrati A, Sarafoff N. Duration of Triple Therapy in Patients Requiring Oral Anticoagulation After Drug-Eluting Stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015 Apr 28;65(16):1619-1629. doi: 10.1016/j.jacc.2015.02.050.

Fiedler KA, Byrne RA, Schulz S, Sibbing D, Mehilli J, Ibrahim T, Maeng M, Laugwitz KL, Kastrati A, Sarafoff N. Rationale and design of The Intracoronary Stenting and Antithrombotic Regimen-Testing of a six-week versus a six-month clopidogrel treatment Regimen In Patients with concomitant aspirin and oraL anticoagulant therapy following drug-Eluting stenting (ISAR-TRIPLE) study. Am Heart J. 2014 Apr;167(4):459-465.e1. doi: 10.1016/j.ahj.2014.01.005. Epub 2014 Jan 14.

• Responsible Party: Deutsches Herzzentrum Muenchen
• ClinicalTrials.gov Identifier: NCT00776633
• Other Study ID Numbers: GE IDE No. A01508
• First Posted: October 21, 2008
• Last Update Posted: August 30, 2016
• Last Verified: August 2014

Keywords provided by Deutsches Herzzentrum Muenchen:

aspirin; clopidogrel; oral anticoagulation; warfarin; drug eluting stent; phenprocoumon

Additional relevant MeSH terms:

Atrial Fibrillation; Coronary Artery Disease; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Coronary Disease; Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular 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