Simvastatin and severe sepsis

ISRCTN	ISRCTN92093279
DOI	https://doi.org/10.1186/ISRCTN92093279
Secondary identifying numbers	Version 2

Submission date: 15/07/2005
Registration date: 01/09/2005
Last edited: 17/05/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr J Duncan Young
Scientific

Adult Intensive Care Unit
John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom

Phone	+44 1865 220621
Email	duncan.young@nda.ox.ac.uk

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Simvastatin and severe Sepsis: a randomised controlled Trial
Study acronym	SimSepT
Study objectives	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(s)	Not provided at time of registration.
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	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 study start date	01/09/2005
Completion date	31/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	104
Key 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.
Key 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
Date of first enrolment	01/09/2005
Date of final enrolment	31/12/2007

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Adult Intensive Care Unit

Oxford
OX3 9DU
United Kingdom

Sponsor information

Oxford Radcliffe Hospitals NHS Trust (UK)
Hospital/treatment centre

Research and Development Office
Manor House
John Radcliffe Hospital
Oxford
OX3 9DU
England
United Kingdom

Phone	+44 (0)1865 222143
Email	emma.tucker@orh.nhs.uk
"ROR"	https://ror.org/03h2bh287

Funders

Funder type

Charity

Moulton Charitable Trust (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

17/05/2017: No publications found in PubMed, verifying study status with principal investigator
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.