Many patients admitted to the Intensive Care Unit (ICU) have a breathing machine, or ventilator, to help them breathe and ensure that enough oxygen gets into their blood. For reasons that are unclear, when people are critically ill their lungs often fail, which is termed acute lung injury (ALI). This study is being conducted to find out if Simvastatin is effective in the treatment of ALI by testing it in a larger number of patients.

Phase 1

• Conditions: Acute lung injury; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2010-020763-20-IE
• Lead Sponsor: ational University of Ireland, Galway

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-04
• Last Update Posted: 9 January 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 540

Inclusion Criteria

1. Patient must be receiving invasive mechanical ventilation
2. Patient must have ALI as defined by acute onset of:
a) hypoxic respiratory failure (PaO2/FiO2 = 40 kPa from 2 arterial blood gases >1 hour apart).
b) bilateral infiltrates on chest X-ray consistent with pulmonary oedema.
c) No clinical evidence of left atrial hypertension or if measured, a pulmonary arterial occlusion pressure (PAOP) less than or equal to 18 mmHg. If a patient has a PAOP > 18 mmHg, then the other criteria must persist for more than 12 hours after the PAOP has declined to < 18 mmHg, and still be within the 48-hour enrolment window

Acute onset is defined as follows: the duration of the hypoxia criterion (a) and the chest X-ray criterion (b) must be <28 days at the time of randomisation.

Infiltrates considered consistent with pulmonary oedema” include any patchy or diffuse infiltrates not fully explained by mass, atelectasis, or effusion or opacities known to be chronic (>28 days). The findings of vascular redistribution, indistinct vessels, and indistinct cardiac borders are not considered consistent with pulmonary oedema”.

All ALI criteria (a-c above) must occur within the same 24 hour period. The time of onset of ALI is when the last ALI criterion is met. Patients must be enrolled within 48 hours of ALI onset

Are the trial subjects under 18? yes
Number of subjects for this age range: 25
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 130
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 115

Exclusion Criteria

1. Age < 16 years
2. More than 48 hours from the onset of ALI
3. Patient is pregnant
4. CK >10 times the upper limit of the normal range*
5. Transaminases >8 times the upper limit of the normal range*
6. Patients currently receiving ongoing and sustained treatment with any of the following; itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, cyclosporine, amiodarone, verapamil or diltiazem. Patients receiving low dose erythromycin as a prokinetic will not be excluded
7. Patients with severe renal impairment (estimated creatinine clearance less than 30ml/minute) not receiving renal replacement therapy
8. Severe liver disease (Child's Pugh score >12; Appendix 1)
9. Current or recent treatment (within 2 weeks) with statins
10. Physician decision that a statin is required for proven indication
11. Contraindication to enteral drug administration, e.g. patients with mechanical bowel obstruction. Patients with high gastric aspirates due to an ileus are not excluded.
12. Domiciliary mechanical ventilation except for CPAP/BIPAP used for sleep-disordered breathing.
13. Known participation in other investigational medicinal product (IMP) trials within 30 days
14. Consent declined
15. Treatment withdrawal imminent within 24 hours
16. Non-english speaking patients or those who do not adequately
understand verbal or written information unless an interpreter is available.
*If CK, ALT and AST values are not available as part of routine care, a blood sample will be obtained after informed consent but before randomisation. CK, ALT, AST values may be obtained up to 72 hours prior to randomisation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified