Intracoronary Stenting and Antithrombotic Regimen: ADjusting Antiplatelet Treatment in PatienTs Based on Platelet Function Testing (ISAR ADAPT PF)

Prospective, Randomized Study of the Platelet Inhibitory Efficacy of Ticagrelor Versus Prasugrel in Clopidogrel Low Responders After Percutaneous Coronary Intervention

Clopidogrel low response is associated with a significantly higher risk for ischemic complications after percutaneous coronary intervention. Ticagrelor and prasugrel are more potent platelet inhibitory drugs and both have been shown to significantly reduce ischemic events as compared to clopidogrel. No direct comparison between ticagrelor and prasugrel in terms of their antiplatelet efficacy exists. The aim of this study is to assess the antiplatelet treatment efficacy of ticagrelor versus prasugrel over time in confirmed clopidogrel low responders undergoing percutaneous coronary intervention.

Study Overview

• Status: Unknown
• Conditions: Coronary Heart Disease
• Intervention / Treatment: Drug: Ticagrelor; Drug: Prasugrel

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Katharina Mayer, MD; Phone Number: +49-89-1218-2020; Email: mayer.katharina@dhm.mhn.de
• Study Contact Backup: Name: Isabell Bernlochner, MD; Phone Number: +49-89-1218-0; Email: isabell.bernlochner@gmx.de

Study Locations

• Germany
  • Bavaria
    • München, Bavaria, Germany, 80636
      • Recruiting
      • Deutsches Herzzentrum
      • Contact: Katharina Mayer, MD; Phone Number: +49-89-1218-2020; Email: mayer.katharina@dhm.mhn.de
      • Contact: Isabell Bernlochner, MD; Phone Number: +49-89-4140-0; Email: isabell.bernlochner@gmx.de
      • Principal Investigator: Katharina Mayer, MD
      • Sub-Investigator: Isabell Bernlochner, MD
    • München, Bavaria, Germany, 81377
      • Recruiting
      • Klinikum der Ludwig-Maximilians-Universität München
      • Contact: Martin Orban, MD; Phone Number: +49 89 7095 2371; Email: martin.Orban@med.uni-muenchen.de
      • Contact: Dirk Sibbing, MD; Phone Number: +49 89 5160 2215; Email: Dirk.Sibbing@med.uni-muenchen.de
      • Principal Investigator: Martin Orban, MD
      • Sub-Investigator: Dirk Sibbing, MD
• Hungary
  • Balatonfüred, Hungary, 8230
    • Not yet recruiting
    • Heart Center Balatonfüred, Dept. of Cardiology
    • Contact: Daniel Aradi, MD; Phone Number: +36302355639; Email: daniel_aradi@yahoo.com
    • Principal Investigator: Daniel Aradi, MD
    • Sub-Investigator: Jozsef Faluközy, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• successful PCI
• 600 mg clopidogrel pretreatment
• clopidogrel low response assessed with electrode aggregometry (>= 486 AU*min)
• written informed consent

Exclusion Criteria:

• Contraindications or allergies against study drugs
• Anemia
• Any surgery < 6 weeks
• Increased bleeding risk
• Oral anticoagulation
• platelet count < 100.000/µl
• Prior history of stroke or pathologic intracranial findings
• GPIIb/IIIa antagonists < 10 days or periprocedural
• Age > 80 years, < 18 years
• Body weight < 60 kg
• Cardiogenic shock
• Increased risk of bradycardia
• Moderate liver disease
• Kidney dialysis
• Intake of CYP 3A4 inhibitors
• Pregnancy or lactation
• Missing pregnancy test for women capable of bearing children

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ticagrelor; A loading dose of 180 mg of ticagrelor is administered followed by 90 mg maintenance doses twice daily	Drug: Ticagrelor; A loading dose of 180 mg of ticagrelor is administered followed by 90 mg maintenance doses twice daily
Active Comparator: Prasugrel; A prasugrel loading dose of 60 mg is administered followed by a 10 mg per day maintenance dose for patients < 75 years or a 5 mg maintenance dose per day for patients >= 75 years	Drug: Prasugrel; A prasugrel loading dose of 60 mg is administered followed by a 10 mg per day maintenance dose for patients < 75 years or a 5 mg maintenance dose per day for patients >= 75 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ADP-induced platelet aggregation after randomized treatment with ticagrelor or prasugrel	Day 2 post randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of low responders in ticagrelor or prasugrel group	Low platelet response is defined as platelet aggregation values >=468 AU*min	Day 2 post randomization
Proportion of enhanced responders in ticagrelor or prasugrel group	Enhanced platelet response is defined as platelet aggregation values <= 188 AU*min	Day 2 post randomization

Collaborators and Investigators

• Sponsor: Deutsches Herzzentrum Muenchen
• Investigators: Principal Investigator: Katharina Mayer, MD, Deutsches Herzzentrum München; Principal Investigator: Martin Orban, MD, Klinikum der Ludwig-Maximilian-Universität München, Campus Großhadern; Principal Investigator: Daniel Aradi, MD, Heart Center Balatonfüred, Dept. of Cardiology

Publications and helpful links

General Publications

• Sibbing D, Braun S, Morath T, Mehilli J, Vogt W, Schomig A, Kastrati A, von Beckerath N. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol. 2009 Mar 10;53(10):849-56. doi: 10.1016/j.jacc.2008.11.030.
• Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. doi: 10.1056/NEJMoa0706482. Epub 2007 Nov 4.
• Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators; Freij A, Thorsen M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57. doi: 10.1056/NEJMoa0904327. Epub 2009 Aug 30.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): April 1, 2014
• Study Completion (Anticipated): May 1, 2014

Study Registration Dates

• First Submitted: October 18, 2011
• First Submitted That Met QC Criteria: October 18, 2011
• First Posted (Estimate): October 20, 2011

Study Record Updates

• Last Update Posted (Estimate): November 1, 2013
• Last Update Submitted That Met QC Criteria: October 31, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: platelet aggregation; prasugrel; ticagrelor; clopidogrel low response
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary 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; Ticagrelor; Prasugrel Hydrochloride
• Other Study ID Numbers: GE-DHM A01811