Safety and Efficacy of Six Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE)

Randomized, Double-Blind, Placebo-controlled Trial of 6 vs. 12 Months Clopidogrel Therapy After Implantation of a Drug-Eluting Stent

The purpose of this study is to determine whether a 6 month duration of clopidogrel therapy after DES implantation is not inferior to that of a 12 month therapy.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Clopidogrel; Drug: Placebo

Detailed Description

Drug elution from stent struts is associated with less smooth muscle cell proliferation and delayed stent strut re-endothelialization. Thus it seems conceivable that a longer duration of dual antiplatelet therapy (aspirin and clopidogrel) after DES implantation is needed. However, no studies have been done to investigate which is the optimal antiplatelet therapy duration after DES implantation. Therefore, the objective of the randomized, double-blind, placebo-controlled ISAR-SAFE study is to evaluate the safety and efficacy of a 6 month versus a 12 month duration of clopidogrel therapy after DES implantation.

Patients on clopidogrel therapy at least 6 months after DES implantation, who do not require a reintervention will be randomized to an additional 6 month period of clopidogrel or placebo. The patients will be followed-up for 9 months after randomization.

• Study Type: Interventional
• Enrollment (Actual): 4005
• Phase: Phase 4

Contacts and Locations

Study Locations

• Albania
  • Tirana, Albania
    • Spitali Gjerman
• Austria
  • Wien, Austria, 1030
    • Krankenanstalt Rudolfstiftung
  • Wien, Austria, 1160
    • Wilhelminenspital Wien
• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven
• China
  • Shenyang, China, 110016
    • Shenyang Northern Hospital
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
• Germany
  • Bad Krozingen, Germany, 79189
    • Herzzentrum Bad Krozingen
  • Bad Segeberg, Germany, 23795
    • Segeberger Kliniken GmbH
  • Berlin, Germany, 12203
    • Charité Berlin, Campus Benjamin Franklin
  • Dresden, Germany, 01309
    • Technische Universität Dresden
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Garmisch-Partenkirchen, Germany, 82467
    • Klinikum Garmisch-Partenkirchen
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen
  • Ingolstadt, Germany, 85049
    • Klinikum Ingolstadt
  • Lahr, Germany, 77933
    • MediClin Herzzentrum Lahr/Baden
  • Landshut, Germany, 84036
    • Krankenhaus Landshut-Achdorf
  • Leipzig, Germany, 04289
    • Herzzentrum Leipzig
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • Munich, Germany, 81541
    • Deutsches Herzzentrum München
  • Munich, Germany, 81675
    • 1st Medizinische Klinik, Klinikum rechts der Isar
  • Munich, Germany, 81925
    • Klinikum Bogenhausen
  • München, Germany, 81377
    • Klinikum München-Großhadern
  • München, Germany, 81737
    • Städtisches Klinikum München-Neuperlach
  • Neuss, Germany, 41464
    • Lukaskrankenhaus GmbH, Städtische Kliniken Neuss
  • Regensburg, Germany, 93042
    • Universitätsklinikum Regensburg
  • Regensburg, Germany, 93049
    • Klinikum Barmherzige Brüder Regensburg
  • Rostock, Germany, 18057
    • Universitätsklinik Rostock
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm
  • Wuppertal, Germany, 42117
    • HELIOS Klinikum Wuppertal-Herzzentrum
• Ireland
  • Galway, Ireland
    • University College Hospital Galway
• Italy
  • Rome, Italy, 00128
    • Campus Biomedico University of Rome
• Japan
  • Isehara, Japan, 259 - 1193
    • Tokai University School of Medicine
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
• Netherlands
  • Eindhoven, Netherlands, 5623
    • Catharina Hospital Eindhoven
  • Nieuwegein, Netherlands, 3435
    • St. Antonius Hospital Department of Cardiology
  • Rotterdam, Netherlands, 3075
    • Maasstad ziekenhuis
  • Zwolle, Netherlands, 8011
    • Isala klinieken, locatie Weezenlanden
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Universitätsspital Bern
• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida, Health Science Center - Jacksonville

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients on clopidogrel therapy at 6 months (-1/+2 months) after DES implantation
• Informed, written consent by the patient

Exclusion Criteria:

• Age ≤18 years
• Clinically symptoms, proof of ischemia and/or presence of angiographic lesions requiring revascularization
• Previous stent thrombosis
• DES in left main coronary artery
• ST-elevation and non-ST-elevation myocardial infarction during the last 6 months
• Malignancies or other comorbid conditions with a life expectancy of less than one year or that may result in protocol noncompliance
• Planned major surgery within the next 6 months with the need to discontinue antiplatelet therapy
• Active bleeding; bleeding diathesis; history intracranial bleeding
• Oral anticoagulation therapy with coumadin derivatives
• Known allergy or intolerance to the study medications: aspirin and clopidogrel
• Pregnancy (present, suspected or planned) or positive pregnancy test (In women with childbearing potential a negative pregnancy test is mandatory)
• Patient's inability to fully comply with the study protocol
• Prior enrollment in the same clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Patients randomized in this group will receive placebo for 6 months.
Active Comparator: Clopidogrel	Drug: Clopidogrel; Patients on clopidogrel therapy at 6 months after implantation of a drug-eluting stent will be randomized to an additional 6 month period of clopidogrel 75mg per day; Other Names: Plavix; ACT-Code: B01AC/04

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite of death, myocardial infarction, stent thrombosis, stroke or TIMI major bleeding.	9 months after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
The individual components of the primary endpoint	9 months after randomization

Collaborators and Investigators

• Sponsor: Deutsches Herzzentrum Muenchen
• Investigators: Study Chair: Adnan Kastrati, MD, Deutsches Herzzentrum Muenchen; Principal Investigator: Jurriёn M ten Berg, MD, St. Antonius Hospital Nieuwegein, Department of Cardiology

Publications and helpful links

General Publications

• Schulz-Schupke S, Byrne RA, Ten Berg JM, Neumann FJ, Han Y, Adriaenssens T, Tolg R, Seyfarth M, Maeng M, Zrenner B, Jacobshagen C, Mudra H, von Hodenberg E, Wohrle J, Angiolillo DJ, von Merzljak B, Rifatov N, Kufner S, Morath T, Feuchtenberger A, Ibrahim T, Janssen PW, Valina C, Li Y, Desmet W, Abdel-Wahab M, Tiroch K, Hengstenberg C, Bernlochner I, Fischer M, Schunkert H, Laugwitz KL, Schomig A, Mehilli J, Kastrati A; Intracoronary Stenting and Antithrombotic Regimen: Safety And EFficacy of 6 Months Dual Antiplatelet Therapy After Drug-Eluting Stenting (ISAR-SAFE) Trial Investigators. ISAR-SAFE: a randomized, double-blind, placebo-controlled trial of 6 vs. 12 months of clopidogrel therapy after drug-eluting stenting. Eur Heart J. 2015 May 21;36(20):1252-63. doi: 10.1093/eurheartj/ehu523. Epub 2015 Jan 23.

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Anticipated): November 1, 2014
• Study Completion (Anticipated): November 1, 2014

Study Registration Dates

• First Submitted: April 15, 2008
• First Submitted That Met QC Criteria: April 17, 2008
• First Posted (Estimate): April 18, 2008

Study Record Updates

• Last Update Posted (Estimate): October 9, 2014
• Last Update Submitted That Met QC Criteria: October 8, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Clopidogrel; Drug-eluting stent
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: GE IDE No. A01207