Condition category
Infections and Infestations
Date applied
15/07/2005
Date assigned
01/09/2005
Last edited
08/09/2014
Prospective/Retrospective
Prospectively 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 J Duncan Young

ORCID ID

Contact details

Adult Intensive Care Unit
John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom
+44 (0)1865 220621
duncan.young@nda.ox.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Version 2

Study information

Scientific title

Acronym

SimSepT

Study hypothesis

Administration of 40 mg simvastatin to patients with severe sepsis reduces plasma concentration of interleukin-6 (IL-6) compared with patients receiving placebo.

Please note that as of 10/10/2007 this trial record was updated with the following changes: two trial centres were added (Royal Sussex County Hospital and the Royal Berkshire Hospital), point ten of the exclusion criteria was updated, the anticipated end date of the trial was extended (previously 01/09/2007), and the interventions were slightly amended.

Ethics approval

Not provided at time of registration.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Severe sepsis

Intervention

Patients will receive a single tablet of either simvastatin 40 mg or identical placebo daily for 7 days (removed from protocol as of 10/10/2007: or until discharge from intensive care, whichever occurs earlier). If the patient is able to swallow, the tablet will be given orally. Otherwise, it will be crushed, suspended in water and administered via any existing enteral feeding or gastric drainage tube. Patients who are unable to receive enteral medications within 24-hours of first organ dysfunction will not be eligible for entry into the trial. All other management decisions will be at the discretion of the treating physician.

Intervention type

Drug

Phase

Not Applicable

Drug names

Simvastatin

Primary outcome measures

The difference in plasma IL-6 concentration between simvastatin and placebo treated groups, on day 3 of treatment. Plasma IL-6 will be measured using a commercially available enzyme linked immunosorbent assay (ELISA) kit. This technique has been used in other recent studies and is familiar to research staff in the department.

Secondary outcome measures

Inflammatory markers
Change in:
1. IL-6 concentration from baseline on days 1, 3 and 7 of treatment
2. C-Reactive Protein (CRP) concentration from baseline on days 1, 3 and 7 of treatment
3. Neutrophil count from baseline on days 1, 3 and 7 of treatment
4. Procalcitonin concentration from baseline on days 1, 3, and 7 of treatment

Infective complications
1. Antibiotic-free days during intensive care unit (ICU) admission
2. Number of new/nosocomial infections defined using National Institutes of Health (NIH) definitions

Safety
1. Number of patients withdrawn due to suspected drug reaction
2. Number of patients withdrawn due to muscle complications (CK ≥five-times ULN, myalgia, myositis, myopathy)
3. Number of patients withdrawn due to elevated plasma aspartate levels
4. Difference in mean plasma CK between groups

Mortality
1. ICU mortality
2. 30-day mortality
3. Hospital mortality

Disease severity
1. SOFA scores days 1, 3 and 7
2. Length of stay
3. ICU length of stay
4. Hospital stay

Compliance/efficacy
1. Plasma low density lipoprotein (LDL) concentration
2. High density lipoprotein (HDL)/LDL ratio

Overall trial start date

01/09/2005

Overall trial end date

31/12/2007

Reason abandoned

Eligibility

Participant inclusion criteria

Patients eligible for inclusion:
1. Those admitted to the Adult Intensive Care Unit at John Radcliffe Hospital, Royal Sussex County Hospital and the Royal Berkshire Hospital (last two centres added 10/10/2007)
2. Severe sepsis or develop severe sepsis whilst in intensive care

Patients must be randomised and receive the first dose of simvastatin within 24 hours of first organ dysfunction to be included in the study.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

104

Participant exclusion criteria

Patients will be excluded from the trial if they:
1. Are receiving simvastatin or another statin prior to admission
2. Refuse consent or their relatives refuse assent
3. Are less than 16 years of age
4. Are included in another interventional study
5. Have a known adverse reaction to statins
6. Have an indication or contraindication to treatment with a statin, according to the treating physician
7. Are unable to receive enteral medications
8. Are receiving drugs known to interact with simvastatin
9. Have active liver disease
10. Have severe renal impairment (anuria) (removed from protocol as of 10/10/2007: creatinine >400 µmol.l^-1 or requirement for renal replacement therapy despite adequate haemodynamic resuscitation)
11. Are at high risk of rhabdomyolysis [multiple trauma, crush injuries, extensive burns, baseline creatinine kinase (CK) ≥five-times upper limit of normal (ULN)]
12. Have a history of known or suspected porphyria
13. Are unlikely to survive more than 24 hours
14. Are unable to speak English (or whose relatives are unable to speak English) and a suitable interpreter cannot be found

Recruitment start date

01/09/2005

Recruitment end date

31/12/2007

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Adult Intensive Care Unit
Oxford
OX3 9DU
United Kingdom

Sponsor information

Organisation

Oxford Radcliffe Hospitals NHS Trust (UK)

Sponsor details

Research and Development Office
Manor House
John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom
+44 (0)1865 222143
emma.tucker@orh.nhs.uk

Sponsor type

Government

Website

Funders

Funder type

Charity

Funder name

Moulton Charitable Trust (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

Publication citations

Additional files

Editorial Notes