E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
cardiac complications during and after vascular surgery |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028601 |
E.1.2 | Term | Myocardial ischemia |
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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 |
to compare hemodynamic stability in patients treated with esmolol versus placebo as an add-on to standard perioperative care. |
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E.2.2 | Secondary objectives of the trial |
-to compare incidence of myocardial ischemia in patients treated with esmolol versus placebo as an add-on to standard perioperative care. -comparing safety parameters such as incidence of bradycardia, TIA and stroke in patients receiving esmolol and standard care versus placebo and standard care. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are eligible for inclusion for the study at the Erasmus Medical Centre if they are: 1. Scheduled for arterial vascular surgery, including abdominal aortic aneurysm repair, abdominal aortic stenosis surgery, lower limb arterial reconstruction or carotid artery stenosis repair 2. Provide informed consent
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E.4 | Principal exclusion criteria |
Potential subjects will be excluded with any of the following: 1. Active bleeding 2. Untreated left main disease 3. Active cardiac condition such as unstable angina pectoris, active congestive heart failure, serious cardiac arrhythmias, symptomatic valvular disease, recent MI< 6 months. 4. Preoperative positive troponin T 5. Contraindication for esmolol use 6. Previous allergy or intolerance to esmolol 7. Cancer with an expected life expectancy < 6 months 8. Excessive alcohol use 9. Pregnancy or planning to become pregnant 10. Failure to provide informed consent 11.Failure to monitor heart rate with the continuous 12-lead electrocardiography because of surgery or baseline electrocardiographic abnormalities. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is hemodynamic stability during the first 24 hours after the start of surgery, where hemodynamic stability is defined as total length of heart rate outside the target window presented in minutes. The target window is defined as a heart rate between 60 and 80 beats per minute. If the heart rate is outside the target window, but without evidence of ischaemia, and esmolol or placebo is titrated at the maximum dose of 300 ug/kg/min, no additional actions will be taken, unless myocardial ischaemia is observed. I.e. if a patient does not experience myocardial ischaemia as assessed by electrocardiographic monitoring, no rescue medication will be provided. However, if the patient develops tachycardia with the presence of signs of ischaemia, a study endpoint is reached, and intervention with rescue medication is performed, in accordance with good clinical practices at the hospital. For those patients in whom the rescue medications were given, there is no additional statistical measurement will be considered to count for the minimum impact on the primary endpoint- differences in total length of heart rate outside the target heart rate window between two groups (bisoprolol vs. bisoprolol + esmolol). Since all patients who are receiving bisoprolol as a minimum standard of care are expected to have relatively low incident rate for signs of ischeamia where additional rescue medication would be used.
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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 | 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 | 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) | 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 | 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.8.3 |
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 | Information not present in EudraCT |
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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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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |