Condition category
Respiratory
Date applied
29/04/2008
Date assigned
09/06/2008
Last edited
30/06/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Danny McAuley

ORCID ID

Contact details

Intensive Care Unit
Royal Victoria Hospital
Grosvenor Road
Belfast
BT12 6BA
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

060778SE-A

Study information

Scientific title

Acronym

Study hypothesis

Treatment with a clinically relevant dose of simvastatin will reduce pulmonary inflammation induced by lipopolysaccharide (LPS) inhalation in humans.

Ethics approval

Office for Research Ethics Committees Northern Ireland (ORECNI). Date of approval: 25/10/2006 (ref: 06/NIR02/91)

Study design

Prospective, randomised, double-blind, placebo-controlled trial.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Acute lung injury (ALI)

Intervention

Subjects will be randomised to the following three arms:
Arm 1: Simvastatin 40 mg enterally for 4 days prior to inhalation of LPS
Arm 2: Simvastatin 80 mg enterally for 4 days prior to inhalation of LPS
Arm 3: Placebo enterally for 4 days prior to inhalation of LPS

Intervention type

Drug

Phase

Not Specified

Drug names

simvastatin

Primary outcome measures

Reduction in broncho alveolar lavage (BAL) Interleukin-8 (IL8) concentration at 6 hours

Secondary outcome measures

1. To investigate whether treatment with simvastatin will modulate the following:
1.1. Alveolar inflammatory response at 6 hours
1.2 Plasma inflammatory response at 24 hours
1.3. Alveolar matrix metalloproteinase activity at 6 hours
1.4. Intracellular signalling in the alveolar space at 6 hours
1.5. Indices of alveolar epithelial and endothelial function and injury at 6 hours
2. To determine the potential mechanisms by which simvastatin may be beneficial in ALI

Overall trial start date

02/08/2006

Overall trial end date

05/11/2009

Reason abandoned

Eligibility

Participant inclusion criteria

Healthy subjects, both males and females

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

30

Participant exclusion criteria

1. Age <18 years
2. Creatinine kinase (CK) >5 times upper limit of normal
3. Known active liver disease
4. Alcohol abuse or abnormal liver function tests: transaminases > 3 times upper limit of normal
5. Renal impairment (calculated creatinine clearance less than 60 mL/minute)
6. History of asthma, known lactose intolerance
7. Participation in other trials within the past 30 days
8. Pregnancy, breast-feeding or women of childbearing potential not using adequate contraception;
9. Current treatment with statins
10. Known hypersensitivity to the study medication
11. Previous adverse reaction to statins
12. Concomitant use of fibrates or other lipid-lowering therapy
13. Concomitant use of itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, nefazodone, grapefruit juice, cyclosporine, danazol, amiodarone, verapamil or diltiazem
14. Consent declined

Recruitment start date

02/08/2006

Recruitment end date

05/11/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Intensive Care Unit
Belfast
BT12 6BA
United Kingdom

Sponsor information

Organisation

Belfast Health and Social Care Trust (UK)

Sponsor details

51 Lisburn Road
Belfast
BT9 7AB
United Kingdom
+44 (0)28 90 329241
rosemary.mcveigh@belfasttrust.hscni.net

Sponsor type

Government

Website

http://www.belfasttrust.hscni.net

Funders

Funder type

Government

Funder name

Intensive Care Society, Young Investigator's Award (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

REVIVE (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Northern Ireland Health and Social Services Central Services Agency (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19324974

Publication citations

  1. Results

    Shyamsundar M, McKeown ST, O'Kane CM, Craig TR, Brown V, Thickett DR, Matthay MA, Taggart CC, Backman JT, Elborn JS, McAuley DF, Simvastatin decreases lipopolysaccharide-induced pulmonary inflammation in healthy volunteers., Am. J. Respir. Crit. Care Med., 2009, 179, 12, 1107-1114, doi: 10.1164/rccm.200810-1584OC.

Additional files

Editorial Notes