Clinical trial NCT01959451: Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment For Acute Coronary Syndromes Trial
Official title: Platelet Function Guided Prasugrel Therapy in ACS Patients Undergoing PCI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Keywords: Prasugrel
Clopidogrel
Lead sponsor: LMU Klinikum
Sponsor class: OTHER
First posted: 2013-10-10
Enrollment: 2600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study investigates whether a platelet function testing guided approach with a short-term (1 week) prasugrel treatment and a switch over to clopidogrel treatment in adequate responders to clopidogrel is non-inferior regarding the combined incidence of bleeding and thrombotic complications to a 12 month standard treatment with prasugrel in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI).

Detailed description: Patients suffering of heart attack have highly activated blood platelets. During and after invasive treatment of blocked coronary vessels (percutaneous coronary intervention = PCI) a potent platelet inhibition is needed to reduce the risk of thrombotic complications which is particularly high within the first week after PCI. On the other hand, the use of potent platelet inhibitors such as prasugrel is associated with higher bleeding risk particularly when used at long-term. A combination of a potent antiplatelet drug (prasugrel) within the first week with a less potent antiplatelet drug (clopidogrel) thereafter might lead to a higher net clinical benefit - means less bleeding and thrombotic complications. This hypothesis is being investigated in the current trial.

Eligibility criteria: Inclusion Criteria:

* Patients with Troponin positive ACS
* Successful PCI (defined as a post PCI diameter stenosis \<20% and TIMI flow ≥2)
* A planned treatment of Prasugrel for 12 months after the procedure
* written informed consent

Exclusion Criteria:

* Age \<18 years and \>80 years
* Subjects with known contraindications to Clopidogrel treatment, which are hypersensitivity to the drug substance or any component of the product and active pathological bleeding such as peptic ulcer or intracranial hemorrhage
* Subjects with known contraindications to Prasugrel treatment, which are hypersensitivity to the drug substance or any component of the product, active pathological bleeding such as peptic ulcer or intracranial hemorrhage and a history of prior transient ischemic attack (TIA) or stroke
* Cardiogenic shock
* Subjects requiring concomitant treatment with an anticoagulant agent (Vitamin-K antagonists or novel oral anticoagulants such as Rivaroxaban, Dabigatran or Apixaban)
* Indication for major surgery (per decision of the treating physician) for the planned duration of the study
* Simultaneous participation in another clinical trial or participation in any clinical trial involving administration of an investigational medicinal product within 30 days prior to clinical trial beginning
* Known or persistent abuse of medication, drugs or alcohol
* Current or planned pregnancy or nursing women, women 90 days after childbirth. Females of childbearing potential, who do not use and are not willing to use medically reliable methods of contraception for the entire study duration (such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices) unless they are surgically sterilized / hysterectomized or there are any other criteria considered sufficiently reliable by the investigator in individual cases
* Evidence of significant active neuropsychiatric disease, in the investigator's opinion

Primary outcomes:
measure: Composite of death from cardiovascular cause, myocardial infarction, stroke and bleeding grade ≥ 2 defined according to BARC criteria
timeFrame: 12 months
Secondary outcomes:
measure: bleeding events BARC class ≥2
timeFrame: 12 months
measure: stent thrombosis
timeFrame: 12 months
measure: all-cause death
timeFrame: 12 months
Other outcomes:
measure: economic impact of a platelet function testing guided tailored treatment for ACS patients
timeFrame: 12 months
Locations:
city: Graz
country: Austria
facility: Medizin-Universität Graz, Univ. Klinik für Innere Medizin
city: Vienna
country: Austria
facility: Wilhelminenspital Wien, 3. Medizinische Abteilung
city: Augsburg
country: Germany
facility: Klinikum Augsburg, Department of Cardiology
city: Bad Krozingen
country: Germany
facility: Heart Center Bad Krozingen
city: Bad Tölz
country: Germany
facility: Asklepios Stadtklinik Bad Tölz, Internal Medicine
city: Bochum
country: Germany
facility: St. Josef Hospital, Katholisches Klinikum Bochum, Department of Cardiology
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt, Department of Cardiology
city: Füssen
country: Germany
facility: Kliniken Ostallgäu-Kaufbeuren, Klinik Füssen
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald, Klinik u. Poliklinik für Innere Medizin B
city: Göttingen
country: Germany
facility: Heart Center at the University Medical Center Goettingen
city: Hamburg
country: Germany
facility: Universitäres Herzzentrum Hamburg, UKE
city: Köln
country: Germany
facility: Herzzentrum der Universität zu Köln
city: Mainz
country: Germany
facility: University Hospital Mainz, Department of Cardiology
city: Memmingen
country: Germany
facility: Klinikum Memmingen, Innere Medizin I
city: Munich
country: Germany
facility: Munich University Hospital
city: Munich
country: Germany
facility: Klinikum Neuperlach, Department of Cardiology
city: Munich
country: Germany
facility: Klinikum Bogenhausen, Department of Cardiology
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg gGmbH, Herz-Kreislauf-Zentrum, Klinik für Kardiologie
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock, Zentrum für Innere Medizin
city: Siegburg
country: Germany
facility: Helios-Klinikum Siegburg, Abteilung für Kardiologie und Angiologie
city: Tuebingen
country: Germany
facility: University Hospital of Tuebingen, Department of Cardiology
city: Weiden
country: Germany
facility: Kliniken Nordoberpfalz AG, Klinikum Weiden, Medizinische Klinik II
city: Budapest
country: Hungary
facility: Semmelweis Egyetem Kardiovaszkuláris Centrum
city: Budapest
country: Hungary
facility: Budapest Military Hospital
city: Budapest
country: Hungary
facility: Heart Center Balatonfüred
city: Györ
country: Hungary
facility: Department of Cardiology Petz Aladár Megyei Oktató Kórház
city: Kecskemet
country: Hungary
facility: Heart Center Kecskemet
city: Pecs
country: Hungary
facility: PTE KK Szívgyógyászati Klinika Intervenciós Kardiológia Részleg
city: Szeged
country: Hungary
facility: Heart Center Szeged
city: Katowice
country: Poland
facility: 3rd Department of Cardiology, Upper Silesian Medical Centre, Medical University of Silesia, Katowice
city: Poznan
country: Poland
facility: 1st Department of Cardiology, Poznan University of Medical Science
city: Warsaw
country: Poland
facility: 1st Department of Cardiology, Medical University of Warsaw
city: Warsaw
country: Poland
facility: Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw
Study officials:
affiliation: Munich University Hospital
name: Dirk Sibbing, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Munich University Hospital
name: Julinda Mehilli, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Munich University Hospital
name: Steffen Massberg, MD
role: STUDY_CHAIR
References:
citation: Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, Orban M, Hadamitzky M, Merkely B, Kiss RG, Komocsi A, Dezsi CA, Holdt L, Felix SB, Parma R, Klopotowski M, Schwinger RHG, Rieber J, Huber K, Neumann FJ, Koltowski L, Mehilli J, Huczek Z, Massberg S; TROPICAL-ACS Investigators. Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial. Lancet. 2017 Oct 14;390(10104):1747-1757. doi: 10.1016/S0140-6736(17)32155-4. Epub 2017 Aug 28.
citation: Sibbing D, Aradi D, Jacobshagen C, Gross L, Trenk D, Geisler T, Orban M, Gori T, Hadamitzky M, Merkely B, Kiss RG, Komocsi A, Dezsi CA, Thalmeier A, Low A, Holdt L, Teupser D, Ince H, Felix SB, Parma R, Malek L, Horstkotte J, Baylacher M, Schwinger R, Rieber J, Mudra H, Hausleiter J, Huber K, Neumann FJ, Koltowski L, Huczek Z, Mehilli J, Massberg S; TROPICAL-ACS Investigators. 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. Thromb Haemost. 2017 Jan 5;117(1):188-195. doi: 10.1160/TH16-07-0557. Epub 2016 Sep 22.