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

Tracking Information

• First Submitted Date: October 20, 2008
• First Posted Date: October 21, 2008
• Last Update Posted Date: August 30, 2016
• Study Start Date: September 2008
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 20, 2008): Composite of death, myocardial infarction, definite stent thrombosis, stroke or major bleeding. [ Time Frame: 9 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 20, 2008)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Triple Therapy in Patients on Oral Anticoagulation After Drug Eluting Stent Implantation
• 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
• 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.
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Coronary Artery Disease
• Atrial Fibrillation

Intervention

• 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

Study Arms

• Experimental: Short triple
  6 weeks triple therapy
  Interventions:

  • Drug: aspirin
  • Drug: clopidogrel
  • Drug: oral anticoagulation
• Active Comparator: Long triple
  6 months triple therapy
  Interventions:

  • Drug: aspirin
  • Drug: clopidogrel
  • Drug: oral anticoagulation

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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: August 28, 2014): 614
• Original Estimated Enrollment (submitted: October 20, 2008): 600
• Estimated Study Completion Date: September 2014
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Germany

Administrative Information

• NCT Number: NCT00776633
• Other Study ID Numbers: GE IDE No. A01508
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Deutsches Herzzentrum Muenchen
• Original Responsible Party: Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München
• Current Study Sponsor: Deutsches Herzzentrum Muenchen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Deutsches Herzzentrum Muenchen
• Verification Date: August 2014