E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
We are investigating the phenomenon of ischaemic-reperfusion injury. Reperfusion of the ischaemic myocardium is known to cause further myocardial damage. We wish to investigate the phenomenon of Remote Ischaemic Preconditionoing along with Glyceryl Trinitrate to reduce reperfusion injury. |
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E.1.1.1 | Medical condition in easily understood language |
Restarting blood supply to the heart muscle after it has been stopped is known to be associated with a certain degree of heart muscle damage. We wish to investigate means to reduce this damage. |
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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 | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051624 |
E.1.2 | Term | Myocardial reperfusion injury |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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. Does GTN administered as a continuous (intra-operative intravenous) infusion into a vein reduce injury to the heart muscle in patients undergoing heart-lung bypass Coronary Artery Bypass Graft (CABG) and/or valve surgery?
2. Does RIPC reduce injury to the heart muscle in the presence of GTN administered as a continuous (intra-operative intravenous) infusion into a vein in patients undergoing heart-lung bypass CABG and/or valve surgery? |
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E.2.2 | Secondary objectives of the trial |
1. Does RIPC or GTN reduce post-operative inotrope (drugs used to support the blood pressure) use? 2. Does RIPC or GTN reduce ventilator dependence post operatively? 3. Does RIPC or GTN reduce incidence of Acute Kidney Injury? 4.Does RIPC or GTN reduce incidence of post-operative atrial fibrillation (rhythm disturbance to the heart which increases morbidity and mortality)? 5. Does RIPC or GTN reduce length of ICU stay? 6. Does RIPC or GTN reduce length of hospital stay? Sub-study 1. Does RIPC or GTN improve heart contractile function after the surgery? |
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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 |
Transthoracic echo sub-study Version 1 dated 31/1/2013: Observational pilot study examining the effect of RIPC and GTN on left ventricular ejection fraction. Objective - To collect pilot data through observations of any changes between baseline and post-operative left ventricular ejection fractions determined by trans-thoraic echocardiograms in patients who get routine echocardiograms pre-operatively post-operatively. |
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E.3 | Principal inclusion criteria |
1.Adult patients (>18 years old) undergoing CABG and/or valve surgery involving cardiopulmonary bypass capable of consenting themselves. |
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E.4 | Principal exclusion criteria |
1. Allergies to excipients of IMP and placebo 2. Chronic Renal failure (eGFR<30 ml/min/kg) 3. Severe liver disease 4. Peripheral arterial disease 5. Pregnant or lactating women 6. Any other contraindications to glyceryl trinitrate as per the summary of product characteristics. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure will be cardiac high-sensitivity troponin T release 72 hours area-under-the-curve. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Blood samples will be collected at 0 hours, 6 hours, 12 hours, 24 hours, 48 hours and 72 hours. High sensitivity Troponin T levels will be determined at plotted as a curve against time. The area under the curve will be determined. |
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E.5.2 | Secondary end point(s) |
i. Inotrope/Vasopressor requirements in the perioperative period The inotrope score will be calculated as follows: Dosages (in μg/kg/min) of [Dopamine + Dobutamine] + [(Adrenaline + Noradrenaline + Isoproterenol + Isoproterenol) x 100] + [(Enoximone + Milrinone) x 15]
ii. Ventilator dependence post operatively. The duration of endotracheal intubation will be noted in hours. Re-intubation rates will be calculated by noting down the number of patients requiring re-intubation and comparing this amongst the 4 groups. iii. Incidence of Acute Kidney Injury assessed using biomarkers (Creatinine). Serum creatinine levels will be noted in the first 3 days postoperatively. If a patient requires renal replacement therapy, this will be recorded and comparisons made amongst the groups. Hourly urine output and daily urine volumes for the duration of ITU stay will be recorded. iv. Incidence of post-operative atrial fibrillation. Atrial fibrillation will be diagnosed using ECG. A record of the number of patients developing AF post operatively, the intervention used to treat it and whether or not the patient reverted to sinus rhythm prior to ITU discharge will be documented. v. Length of ICU stay. A record of stay in days will be noted. vi. Length of hospital stay A record of stay in days will be noted. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | No |
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) | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
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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Discharge of the last recruited patient from the hospital. |
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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 | 1 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 1 |