Simvastatin in acute lung injury

Phase 2

Completed

• Conditions: Acute lung injury; Respiratory; Lung injury

• Registration Number: ISRCTN88244364
• Lead Sponsor: Belfast Health and Social Care Trust (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-26
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 540

Inclusion Criteria

Current inclusion criteria as of 14/09/2011:
1. Patient must be receiving invasive mechanical ventilation
2. Patient must have ALI [34] as defined by acute onset of:
2.1 Hypoxic respiratory failure (PaO2/FiO2 = 40 kPa from 2 blood gases >1 hour apart).
2.2 Bilateral infiltrates on chest X-ray consistent with pulmonary oedema.
2.3 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

Previous inclusion crieteria:

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 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.

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.

Exclusion Criteria

Current exclusion criteria as of 07/09/2012:
1. Age < 16 years
2. More than 48 hours from the onset of ALI
3. Patient is known to be 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, HIV protease inhibitors, nefazodone, cyclosporine, amiodarone, verapamil or diltiazem.
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 and AST values may be obtained up to 72 hours prior to randomisation.

Previous exclusion criteria until 07/09/2012:
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.
12. Domiciliary mechanical ventilation
Added 08/03/2011:
16. Non-english speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available

Study & Design

• Study Type: Interventional
• Study Design: Not specified