E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Lung Injury (ALI) and the Acute Respiratory Distress Syndrome (ARDS)
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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 is safe and improves important surrogate clinical outcomes in adult patients with ALI/ARDS. The primary outcome measure will be a reduction in extravascular lung water (EVLW )in the simvastatin treated group at day 7. |
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E.2.2 | Secondary objectives of the trial |
The secondary aims are to measure: 1) physiological severity of lung injury as measured by PaO2:FiO2 ratio at day 7 and respiratory compliance at day 7 2) effects on the pulmonary circulation as measured by change in pulmonary dead space at day 7. 3) extra-pulmonary organ failure as measured by SOFA (Sequential Organ Failure Assessment) score at day 7 4) safety and tolerability as assessed by the occurrence of suspected unexpected serious adverse reactions (SUSAR).
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Mechanically ventilated adult patients admitted to the intensive care unit at the Royal Victoria Hospital, within 48 hours of the onset ALI or ARDS, will be eligible for inclusion in the study. ALI and ARDS will be defined according to the American European Consensus Conference definition . Severe sepsis will be defined as in prior studies . Patients will be prospectively screened daily to see if they fulfil the inclusion criteria for recruitment to the study.
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E.4 | Principal exclusion criteria |
Age < 18 years; pregnancy; creatinine kinase (CK) > 10 times upper limit normal range, transaminases > 3 times upper limit normal range; participation in other intervention trials within previous 30 days; current treatment with statins; contraindication to enteral nutrition; unlikely to survive beyond 48 hours; patients with significant end stage disease as previously defined and assent declined from the next of kin. These criteria are designed to include those critically patients who are likely to benefit from the therapeutic intervention and exclude patients unlikely to benefit from the intervention (not likely to survive beyond 48 hours, patients with significant end stage disease). Patients with ALI/ARDS for more than 48 hours are excluded to evaluate more clearly the effects of simvastatin early in the course of lung injury.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measure will be a reduction in EVLW in the simvastatin treated group at day 7. |
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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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
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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Treatment will be continued until a study endpoint is reached. Study termination criteria will be death; discontinuation of mechanical ventilation; request to withdraw from relative and discontinuation of active treatment. Each subject will be enrolled for a maximum of 14 days. |
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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 | |
E.8.9.1 | In the Member State concerned days | |