E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
ischemia reperfusion injury |
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E.1.1.1 | Medical condition in easily understood language |
therapy of injury to the heart after the interruption of blood supply |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055224 |
E.1.2 | Term | Cardiac ischemia |
E.1.2 | System Organ Class | 100000004849 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023031 |
E.1.2 | Term | Ischemia coronary artery origin |
E.1.2 | System Organ Class | 100000004849 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10023033 |
E.1.2 | Term | Ischemia myocardial |
E.1.2 | System Organ Class | 100000004849 |
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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 |
1) To evaluate the effects of heme arginate administration in two different doses on myocardial HO – 1 induction
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E.2.2 | Secondary objectives of the trial |
2) To evaluate postoperative plasma levels of myoglobin, creatin-kinase, troponin T and reactive oxygen species according to treatment period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Signed informed consent - Men and women aged between 40 and 85 years (inclusive) - Body mass index <35 kg/m2 - Ability to communicate well with the investigator in the local language and to understand and comply with the requirements of the study
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E.4 | Principal exclusion criteria |
- Known hypersensitivity to the study drug or any excipients of the drug formulation - Treatment with another investigational drug within 3 weeks prior to screening - History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug - Severe renal failure (glomerula filtration rate < 30ml/min) - Moderately or severe impaired left ventricular function (ejection fraction < 40%) - Moderately or severe impaired right ventricular function - Systolic pulmonary pressure > 45mmHg - Acute or recent (<7 days) myocardial infarction
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E.5 End points |
E.5.1 | Primary end point(s) |
Main outcome variables HO – 1 mRNA and protein induction in the heart due to heme arginate pretreatment |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
HO – 1 mRNA and protein induction in PMBC in patients undergoing cardiac surgery due to heme arginate pretreatment Evaluate dose-response of HO-1 induction in the heart
Additional outcome Reactive oxygen species levels (Biopsies and blood samples) Postoperative plasma levels of creatine kinase, troponin T and myoglobin
Safety variables Major cardiac adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
until 72 hours after surgery |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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 | 0 |