E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
The hypothesis of the study is that treatment with simvastatin can prevent lung injury and inflammation in humans undergoing oesophagectomy as assessed by important surrogate clinical outcomes.
The primary outcome is to evaluate the efficacy of simvastatin to improve pulmonary vascular function between the simvastatin and placebo treated groups |
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E.2.2 | Secondary objectives of the trial |
The following secondary outcomes will also be assessed: 1) Oxygenation assessed by the PaO2: FiO2 ratio 2) Respiratory system compliance 3) Safety and tolerability
The secondary aims are to investigate if treatment with simvastatin will modulate: 1) biomarkers of alveolar epithelial and endothelial function and injury 2) plasma and pulmonary cytokine response 3) systemic and pulmonary inflammation and oxidative stress to determine the potential mechanisms by which simvastatin may be beneficial in ALI. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adult patients undergoing oesophagectomy for oesophageal cancer at the Royal Victoria Hospital, Belfast (RVH) |
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E.4 | Principal exclusion criteria |
• age < 18 years • creatinine kinase (CK) > 5 times upper limit normal range • known active liver disease (Child’s Pugh score > 11), or abnormal liver function tests: transaminases > 3 times upper limit normal range • renal impairment (calculated creatinine clearance less than 30mL/minute) • inability to take oral medication pre-operatively • known lactose intolerance • participation in other intervention trials within 30 days • pregnancy, breast-feeding or women of childbearing potential not using adequate contraception; • patients taking corticosteroids or non-steroidal anti-inflammatory drugs • current treatment with statins • known hypersensitivity to the study medication • a previous adverse reaction to statins • concomitant use of fibrates or other lipid-lowering therapy • concomitant use of itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, grapefruit juice, cyclosporine, danazol, amiodarone, verapamil or diltiazem. • consent declined |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure will be pulmonary vascular function as measured by pulmonary dead space fraction (Vd/Vt) at 6 hours following one lung ventilation or prior to extubation if earlier between the simvastatin and placebo treated groups
This endpoint was chosen as dysregulated alveolar inflammation causes pulmonary vascular endothelial injury, important in the development of ALI/ARDS. In addition, elevated Vd/Vt is predictive of mortality in ALI/ARDS. The 6 hour time point was chosen as markers of inflammation and oxidative stress can be detected at this time. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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) | 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 | 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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |