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 1865 220621
duncan.young@nda.ox.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Version 2
Study information
Scientific title
Simvastatin and severe Sepsis: a randomised controlled Trial
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.
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 measure
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 (if study stopped)
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
Basic results (scientific)
Publication list