Thromb Haemost 2017; 117(01): 188-195
DOI: 10.1160/TH16-07-0557
Trial Protocol Design Paper
Schattauer GmbH

A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI

Rationale and design of the Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Trial
Dirk Sibbing*
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
2   DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
Dániel Aradi*
3   Heart Center Balatonfüred and Heart and Vascular Center, Semmelweis University Budapest, Hungary
,
Claudius Jacobshagen
4   Department of Cardiology und Pneumology, Heart Center / Georg-August-University Göttingen, Germany
,
Lisa Gross
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
,
Dietmar Trenk
5   University Heart Center Freiburg, Bad Krozingen, Department of Cardiology and Angiology II, Bad Krozingen, Germany
,
Tobias Geisler
6   University Hospital Tübingen, Department of Cardiology and Cardiovascular Disease, Tübingen, Germany
,
Martin Orban
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
,
Tommaso Gori
7   Zentrum für Kardiologie, Kardiologie I, Universitätsmedizin Mainz und DZHK (German Center for Cardiovascular Research), partner site Rhein-Main, Germany
,
Martin Hadamitzky
8   Department of Radiology, Deutsches Herzzentrum München, Germany
,
Béla Merkely
9   Heart and Vascular Center, University of Semmelweis, Budapest, Hungary
,
Róbert Gábor Kiss
10   Department of Cardiology, Military Hospital, Budapest, Hungary
,
András Komócsi
11   Department of Interventional Cardiology, Heart Institute, University of Pécs, Pécs, Hungary
,
Csaba A. Dézsi
12   Department of Cardiology, Petz Aladár County Teaching Hospital, Györ, Hungary
,
Andreas Thalmeier
13   Pharmacy Department, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
,
Anja Löw
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
,
Lesca Holdt
14   Department of Clinical Chemistry, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
,
Daniel Teupser
14   Department of Clinical Chemistry, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
,
Hüseyin Ince
15   Universitätsmedizin Rostock, Zentrum für Innere Medizin, Rostock, Germany
,
Stephan B. Felix
16   Department of Internal Medicine B, University Medicine Greifswald, Germany und DZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany
,
Radoslaw Parma
17   3rdDepartment of Cardiology, Medical University of Silesia, Katowice, Poland
,
Lukasz Malek
18   Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland
,
Jan Horstkotte
19   Helios-Klinikum Siegburg, Abteilung für Kardiologie und Angiologie, Siegburg, Germany
,
Monika Baylacher
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
,
Robert Schwinger
20   Medizinische Klinik II, Klinikum Weiden, Kliniken Nordoberpfalz AG, Weiden, Germany
,
Johannes Rieber
21   Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich, Germany
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
,
Harald Mudra
22   Department of Cardiology, Pulmonology and Internal Intensive Care Medicine, Klinikum Neuperlach, Städtisches Klinikum München GmbH, Munich, Germany
,
Jörg Hausleiter
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
2   DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
Kurt Huber
23   3rdMedical Department, Cardiology and Intensive Care Medicine, and Sigmund Freud Private University. Medical School, Wien, Austria
,
Franz-Josef Neumann
5   University Heart Center Freiburg, Bad Krozingen, Department of Cardiology and Angiology II, Bad Krozingen, Germany
,
Lukasz Koltowski
24   IstDepartment of Cardiology, Medical University of Warsaw, Warsaw, Poland
,
Zenon Huczek
24   IstDepartment of Cardiology, Medical University of Warsaw, Warsaw, Poland
,
Julinda Mehilli
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
2   DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
Steffen Massberg
1   Department of Cardiology, Ludwig-Maximilians-Universität München (LMU Munich), Munich, Germany
2   DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
,
on behalf of the TROPICAL-ACS Investigators › Author Affiliations
Financial support: TROPICAL-ACS is an independent, Investigator-Initiated trial with an academic sponsor (Ludwig-Maximilians-Universität München). The trial is financially supported by a research grant from Roche Diagnostics (Rotkreuz, Switzerland). Prasugrel purchase, drug delivery and related logistics were kindly supported by Eli Lilly and Company and Daiichi Sankyo Company.
Further Information

Publication History

Received: 21 July 2016

Accepted after major revision: 09 September 2016

Publication Date:
01 December 2017 (online)

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Summary

Outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) have been significantly improved with the use of potent P2Y12 receptor inhibitors like prasugrel. While most of the ischaemic risk reduction for prasugrel versus clopidogrel was demonstrated in the early treatment period, the risk of bleeding became particularly prominent during the chronic course of therapy. It may therefore be a valid approach to substitute prasugrel for clopidogrel in the early phase of chronic antiplatelet treatment after PCI. In the Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial, we aim to compare standard prasugrel therapy with a de-escalating antiplatelet treatment approach guided by platelet function testing (PFT). The study is an investigator-initiated European multicentre, randomised clinical trial in biomarker-positive ACS patients after successful PCI. Two thousand six hundred patients will be randomised prior to hospital discharge in a 1:1 fashion to either receive standard prasugrel therapy (control group) or de-escalating therapy (one-week prasugrel followed by one-week clopidogrel and PFT-guided maintenance therapy from day 14 after hospital discharge, monitoring group). Patients of the monitoring group with high on-clopidogrel platelet reactivity (HPR) based on Multiplate analyzer testing (HPR: ≥ 46U per consensus definition) will be switched back to prasugrel, whereas those without HPR (<46 U) will continue clopidogrel treatment. The overall study treatment duration will be one year in both groups. The primary endpoint of the study is net clinical benefit (combined incidence of cardiovascular death, myocardial infarction, stroke and bleeding ≥ grade 2 according to BARC criteria) one-year after randomisation. TROPICAL-ACS is the first large-scale, randomised controlled trial assessing the clinical value of a PFT-guided de-escalation of antiplatelet treatment in biomarker positive ACS patients undergoing PCI.

ClinicalTrials.gov Identifier: NCT01959451

* D. S. and D. A. contributed equally to this work.