Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP)

Completed

• Conditions: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS); Respiratory; Acute lung injury and acute respiratory distress syndrome (ARDS)

• Registration Number: ISRCTN70127774
• Lead Sponsor: The Royal Group Hospitals Trust (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-04-24
• Last Update Posted: 13 January 2015

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 60

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.

Exclusion Criteria

Current exclusion criteria as of 17/04/2012
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
1. Aged under 18 years
2. Pregnancy
3. Creatinine kinase (CK) more than five times upper limit of normal range
4. Transaminases more than three times upper limit of normal range
5. Participation in other intervention trials within previous 30 days
6. Current treatment with statins
7. Contraindication to enteral nutrition
8. Unlikely to survive beyond 48 hours
9. Patients with significant end stage disease as previously defined and assent declined from the next of kin

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Reduction in extravascular lung water (EVLW) in the simvastatin treated group at day 7