E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Troponin positive acute coronary syndrome after successful percutaneous coronary intervention with an indication for a standard treatment of 12 month with prasugrel |
|
E.1.1.1 | Medical condition in easily understood language |
Troponin positive acute heart attack after successful cardiac catheter treatment with an indication for a standard treatment of 12 month with prasugrel |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051592 |
E.1.2 | Term | Acute coronary syndrome |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
A Platelet function testing guided approach with a short-term (1 week) post hospital discharge prasugrel maintenance dose treatment and a switch-over to clopidogrel treatment in adequate responders to the drug is non-inferior to the currently recommended long-term (12 month) treatment with prasugrel in ACS patients undergoing PCI. |
|
E.2.2 | Secondary objectives of the trial |
- Bleeding events with a grade >= 2 defined according to BARC criteria
- Stent thrombosis (definite or probable) according to ARC (Academic Research Consortium) criteria
- Incidence of urgent ischemia-driven revaccularization
- Incidence of death from any cause
- Pre-specified cost-effectiveness analysis on the economic impact of a platelet function testing guided tailored treatment for ACS patients
- The individual ischemic components of the primary endpoint will be subject to the secondary endpoint analysis
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. TROPICAL-ACS Biomarker Substudy (included in Protocol V. 4.0, date 03. December 2013)
- Identification of novel biomarkers that aid in personalized prediction of patients outcomes. Proteomic, metobolic, RNA expression, DNA polymorphism and methylation screening at genome-wide scale will be used
- Extended platelet function testing with additional activators on day of randomization and day 14 to gain additional insights into correlation of platelet-function parameters and their predictive power
- Combined analysis of biomarkers with platelet function testing to aid in the identification of novel prediction algorithms with potential impact on therapeutic approaches of ACS.
2. Site specific Substudy Protocol for site Mainz and KUM (only valid for site Mainz and KUM V. 1.0, 24. Nov. 2013, Amendment 1 from 02. Apr. 2014, included as appendix 4 of the protocol V 5.0)
- Substudy 1: The relationship between endothelial function and platelet activation
-- Primary aim: To test whether the switch from prasugrel to clopidogrel, as compared to the continued administration of prasugrel, will result in a change in endothelial function, and whether there is a difference between responders and non-responders to clopidogrel.
-- Endpoint of the substudy: Changes in Flow-mediated dilation (FMD) in response to the administration of clopidogrel or prasugrel on day 14 as compared to day 7.
- Substudy 2: Effect of prasugrel versus clopidogrel on the thrombotic-inflammatory potential of platelets assessed by novel surrogate platelet function tests.
-- Investigating the effect of prasugrel versus clopidogrel on the platelet proteomic profile and platelet-leukocyte interaction in terms of responsiveness to clopidogrel.
-- Endpoint of the substudy: Changes in the platelet protein composition and platelet-leukocyte conjugate formation in response to the administration of clopidogrel or prasugrel on day 14 compared to day 7.
Substudy 3: The hemostatic system as a modulator of acute coronary syndromes (ACS): Identification of genetic variants and their correlation with endothelial function, platelet activation and clinical outcome
-- Identification of (novel) genetic variants in genes with crucial functional roles in the hemostatic system including endothelial function and platelet activation (by applying high-through-put sequencing strategies)
-- Correlation with the primary endpoint of the main study: The primary end point of the study is a combined ischemic and bleeding end point, which is a composite endpoint consisting of death from cardiovascular cause (for a definition see appendix 2), myocardial infarction, nonfatal stroke and bleeding grade ≥2 defined according to BARC criteria (see main study protocol for details).
-- Correlation with the following secondary endpoint of the main study:
- Incidence of class ≥2 bleeding events at 12 months
- Bleeding Academic Research Consortium (BARC)
- Incidence of stent thrombosis (combined definite
- defined according to Academic Research Consortium
- Incidence of death from any cause at 12 months
- Incidence of cardiovascular death at 12 months
- Incidence of MI at 12 months
- Incidence of nonfatal stroke at 12 months
-- Correlation with angiographic outcomes.
-- Correlation with endothelial and platelet function (see substudy 1 and 2)
3. SPARTAN Substudy (included in protocol V 5.0 dated 02. Apr. 2014)
- To determine if patients can be safely swtched from Prasugrel to Clopidogrel in LOF non carriers in the chrinic phase after ACS
- To analyze the association of CYP2C19 alleles with on-treatment platelet reactivity (MEA ADP) under Prasugrel treatment
- To test the feasibility and clinical application of rapid point of care genetic testing in the ACS setting
- To evaluate the health economics if this approach
|
|
E.3 | Principal 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 month after the procedure
- Written informed consent |
|
E.4 | Principal 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
- Subjects with a history of a complicated or prolonged cardiogenic shock in the last two weeks prior to the beginning of this clinical trial. A complicated or prolonged cardiogenic shock is defined by a cardiogenic shock that required mechanical ventilation or the cardiovascular support with positive inotropic drugs (i.v. catecholamines) for ≥7 days.
- 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 that involveds the administration of an investigational medicinal drug within 30 days prior to the beginning of this clinical trial
- 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 devices) unless they are surgically sterilized/hysterectomized or there are any other criteria considered sufficiently reliable by the investigator`s opinion
- Evidence of significant active neuropsychiatric disease, in the investigator´s opinion |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Combined ischemic and bleeding endpoint, which is a composite endpoint consisting of death from cardiovascular cause, myocardial infarction, stroke and bleeding grade >= 2 defined according to BARC (Bleeding Academic Research Consortium) criteria |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The time points of evaluation will be Follow up 30 days, 6 month and 12 month. |
|
E.5.2 | Secondary end point(s) |
- Bleeding events with a grade >= 2 defined according to BARC criteria
- Stent thrombosis (definite or probable) according to ARC (Academic Research Consortium) criteria
- Incidence of ischemia-driven revascularization
- Incidence of death from any cause
- Pre-specified cost-effectiveness analysis on the economic impact of a platelet function testing guided tailored treatment for ACS patients
- The individual ischemic components of the primary endpoint will be subject to the secondary endpoint analysis
-- Incidence of cardiovascular death at 12 month
-- Incidence of MI at 12 month
-- Incidence of nonfatal stroke at 12 month
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The time points of evaluation will be Follow up 30 days, 6 month and 12 month. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Since this is a multi-center , multi-national trial with a high amount of clinical data the end of study is defined as data base lock. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |