E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011078 |
E.1.2 | Term | Coronary artery disease |
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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 |
The primary objective is to evaluate the clinical benefit of acadesine in reducing the incidence of ischemia-reperfusion injury resulting from Coronary Artery Bypass Graft CABG surgery, as measured by the first occurrence of any component of the composite primary endpoint of all-cause death, Severe Left Ventricular Dysfunction (SLVD), or non-fatal stroke occurring during or following CABG surgery through Postoperative Day (POD) 28. |
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E.2.2 | Secondary objectives of the trial |
The key secondary objective is to evaulate the clinical benefit of acadesine with respect to incidence of the first occurrence of any component of the composite of cardiovascular death, SLVD, or non-fatal stroke occurring during or following CABG surgery through POD 28. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The subject must meet ALL the criteria listed below for entry: 1. A subject must be a high-risk patient undergoing non-emergency CABG surgery requiring cardiopulmonary bypass and cardioplegia. 2. A subject must be ≥ 50 years of age. 3. A subject must have at least one of the following risk factors: a. Female (but not preganant or lactating), or b. History of prior CABG, or c. History of MI (except for MI within 5 days prior to surgery or MI having occurred more than 2 years previously), or d. History of ischemic stroke, or e. Left ventricular ejection fraction (EF) ≤ 30% (measured any time within the previous 3 months before Screening), or f. Diabetes mellitus requiring insulin and/or antidiabetic agents. 4. A subject must have demonstrated on coronary angiography, performed within the past 12 months, to have significant coronary artery stenosis of at least 50% of the left main coronary artery, or 70% or more of three coronary arteries, or 70% or more of two coronary arteries inclusive of the left anterior descending (LAD). The screening coronary angiography must have been performed after any previous PCI or CABG. 5. A subject must be willing and able to give Informed Consent. 6. A woman of child-bearing potential who is currently sexually active must agree to use a medically accepted method of contraception during screening and for one month after stopping the medication. Medically accepted methods of contraception include condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation). |
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E.4 | Principal exclusion criteria |
The subject will be excluded from entry if ANY of the criteria listed below are met: 1. Subject undergoing planned valve replacement, carotid artery or aortic surgery, distal coronary endarterectomy or ventricular aneurysmectomy, alone or with CABG surgery (repair for mild-to-moderate mitral valve disease with concomitant CABG is not excluded). 2. Subject undergoing CABG surgery using intermittent aortic cross clamping without cardioplegia. 3. Subject undergoing minimally invasive surgery (ie, without use of cardiopulmonary bypass). 4. Subject with an MI within 5 days prior to surgery or greater than 2 years. 5. Subject with a pre-operative intra-aortic balloon pump (IABP), left ventricular assist device (LVAD), extra-corporeal membrane oxygenator (ECMO), or other mechanical hemodynamic assist device. 6. Subjects with a history or presence of gout or uric acid nephrolithiasis. 7. Subjects with a serum creatinine >2 mg/dL (180 umol/L) at Screening. 8. Subjects with a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 X Upper Limit of Normal (ULN) at Screening. 9. Subject who has received any treatment listed in Table 2 (Prohibited medications for Entry into the Study) in the protocol more recently than the indicated washout period prior to surgery or must continue to receive treatment that is listed in Table 2. (Prohibited medications: 24 hr washout period prior to surgery for adenosine, aminophylline, nicotinic acid, pentoxifylline, theophylline, and cardioplegia solutions containing adenosine, dipyridamole, lidoflazine, or lidocaine; 2 day washout period prior to surgery for dipyridamole; 4 day washout period prior to surgery for allopurinol; 30 day washout period prior to Screening for investigational drugs) 10. Administration of food and drinks containing caffeine, theobromines or methlxanthines (such as coffee, tea, colas, some `energy` drinks or chocolate) is not allowed within 24 hours before surgery. 11. Subjects with known allergy/sensitivity to acadesine or its/their excipients. 12. Woman who is breast-feeding, pregnant or intends to become pregnant within 30 days of study drug administration. 13. Subject who has used any investigational drugs within 30 days of Screening. 14. Subject who is participating in any other clinical study. 15. Subject who is part of the staff personnel directly involved with this study or who is a family member of the investigational study staff. 16. Subject with an inability or unwillingness to abide by the protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for the study is the first occurence of any component of the composite of all-cause death, SLVD, or non-fatal stroke occurring during and following CABG surgery through POD 28. The efficacy endpoints are defined as: -All-cause death -severe left ventricular dysfunction (SLVD): new use during or after CABG surgery of intra-aortic balloon pump (IABP) or left ventricular assist device (LVAD) for ≥ one (1) hour for treatment of low cardiac output. Indications for using IABP/LVAD are determined by the attending physician based on his/her clinical judgment. Indications can include but are not limited to cardiogenic shock, support for high-risk cardiac surgery, trouble of weaning from cardiopulmonary bypass, refractory left ventricular failure, refractory ventricular arrhythmias, and other indications that the investigator deem necessary for treatment of low cardiac output. -non-fatal sroke: an acute focal neurological deficit of sudden onset that is not reversible within 24 hours, not due to an identifiable non-vascular cause (ie, brain tumor, trauma), and is accompanied by clear evidence of a new stroke on brain imaging (CT scan or MRI). Please refer to protocol for other endpoints. |
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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 | 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) | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Il farmacista non e` in cieco durante la preparazione del farmaco sperimentale |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
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 | 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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |