E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with coronary heart disease who will be undergoing non-urgent Percutaneous Coronary Intervention (PCI) |
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MedDRA Classification |
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 |
in subjects undergoing non-urgent percutaneous coronary intervention (PCI): · to determine the effect of several intravenous (IV) regimens of otamixaban on the pharmacodynamic marker F1 + F2 (marker of thrombin generation) at the end of the infusion, as compared to IV unfractionated heparin (UFH) · and to determine the effect of several IV regimens of otamixaban on the pharmacodynamic marker anti-factor Xa (anti-FXa) activity at the end of the infusion. |
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E.2.2 | Secondary objectives of the trial |
to identify a safe range of dosages of IV otamixaban in comparison to UFH. Safety and tolerability will include: · assessments of bleeding, based on the incidence of the composite endpoint of TIMI major, minor and minimal bleeding episodes up to Day 3 or hospital discharge (whichever comes first), composite endpoint of TIMI major and minor bleeds, and the components TIMI major bleeds, and TIMI minor bleeds · adverse events (AEs) and laboratory safety data
to assess the effect of several IV regimens of otamixaban on clinical efficacy, as represented by the incidence of the composite endpoint of death, myocardial infarction (MI), and target vessel revascularization (urgent and non-urgent) for 30 days after randomization
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
· Men or women ≥ 18 years of age · Due to undergo non-urgent PCI with a femoral approach, with balloon angioplasty (with or without stent) of a single or multiple sites of native vessel(s) during the same procedure · Planned treatment with aspirin and clopidogrel prior to PCI (unless allergic to one of these medications). · Informed consent obtained in writing at enrollment into the study (oral consent alone is not allowed)
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E.4 | Principal exclusion criteria |
General · Breastfeeding or pregnancy · Inability to give informed consent or high likelihood of being unavailable for Day 31 follow-up · Treatment with other investigational agents (including placebo) or devices within 30 days days prior to enrollment or planned use of investigational drugs or devices during the study Cardiovascular · Onset of acute coronary syndrome (STEMI, unstable angina/NSTEMI) within 48 hours prior to randomization . Ischemic discomfort at rest within 24 hours prior to randomization · Congestive heart failure of New York Heart Association class III or IV at enrollment · Hemodynamic instability at enrollment · Significant valvular disease with hemodynamic impairment · Radial approach for the planned PCI Related to bleeding risk · Active or recent (< 3 months) significant bleeding, including gastrointestinal bleeding or gross hematuria · Ischemic stroke within 12 months or history of any previous hemorrhagic stroke · Known structural damage or other pathologic process involving the central nervous system (including, but not limited to, intracranial tumor or intracerebral vascular malformation) · Recent (< 1 month) trauma (including cardiac resuscitation), major surgery (including bypass surgery) or parenchymal organ biopsy · Uncontrolled arterial hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) · Past or present bleeding disorder (including congenital bleeding disorders such as von Willebrand’s disease or hemophilia, acquired bleeding disorders, or unexplained repeated bleeding episodes) Related to prior/concomitant medications · Chronic daily use of NSAIDs or oral corticosteroids · Thrombolytic therapy within the previous 14 days · History of hypersensitivity or contraindication to unfractionated heparin · Treatment with unfractionated heparin, enoxaparin, nadropirin, dalteparin, reviparin, or bivalirudin within the 12 hours preceding randomization . Treatment with tinzaparin or fondaparinux within 24 hours preceding randomization · Treatment with abciximab within 10 days prior to randomization · Treatment with eptifibatide or tirofiban within 12 hours prior to randomization Laboratory values · Known thrombocytopenia (platelet count ≤ 100 000/μL) at enrollment · Known international normalized ratio (INR) > 1.2 at enrollment · Known estimated creatinine clearance ≤ 30 mL/min at enrollment (Cockroft and Gault formula) · Known clinically significant anemia (hemoglobin < 10 g/dL) at enrollment
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary analysis variables are the following two pharmacodynamic markers: · F1 + F2 (marker of thrombin generation) change from baseline assessed at the end of the 3-hour infusion · anti-FXa activity assessed at the end of the 3-hour infusion
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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The end of the trial is defined as 3 months after the Day 31 telephone contact for the last subject enrolled in order to collect the last case report forms and lock the clinical database. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |