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13 March 2010
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| [ Print-friendly version ] |
| Simvastatin and severe Sepsis: a randomised controlled Trial |
| ISRCTN | ISRCTN92093279 |
| ClinicalTrials.gov identifier | |
| Public title | Simvastatin and severe Sepsis: a randomised controlled Trial |
| Scientific title | |
| Acronym | SimSepT |
| Serial number at source | Version 2 |
| 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 |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Severe sepsis |
| Participants - 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. |
| Participants - 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 |
| Anticipated start date | 01/09/2005 |
| Anticipated end date | 31/12/2007 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 104 |
| Interventions | 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. |
| Primary outcome measure(s) | 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 measure(s) |
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 |
| Sources of funding | Moulton Charitable Trust (UK) |
| Trial website | |
| Publications | |
| Contact name | Dr J Duncan Young |
| Address |
Adult Intensive Care Unit
John Radcliffe Hospital Headley Way |
| City/town | Oxford |
| Zip/Postcode | OX3 9DU |
| Country | United Kingdom |
| Tel | +44 (0)1865 220621 |
| Fax | +44 (0)1865 857611 |
| duncan.young@nda.ox.ac.uk | |
| Sponsor | Oxford Radcliffe Hospitals NHS Trust (UK) |
| Address |
Research and Development Office
Manor House John Radcliffe Hospital |
| City/town | Oxford |
| Zip/Postcode | OX3 9DU |
| Country | United Kingdom |
| Tel | +44 (0)1865 222143 |
| Fax | +44 (0)1865 222699 |
| emma.tucker@orh.nhs.uk | |
| Date applied | 15/07/2005 |
| Last edited | 10/10/2007 |
| Date ISRCTN assigned | 01/09/2005 |
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