Simvastatin and severe sepsis
ISRCTN | ISRCTN92093279 |
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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
Plain English summary of protocol
Not provided at time of registration
Contact information
Scientific
Adult Intensive Care Unit
John Radcliffe Hospital
Headley Way
Oxford
OX3 9DU
United Kingdom
Phone | +44 1865 220621 |
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duncan.young@nda.ox.ac.uk |
Study information
Study design | Randomised controlled trial |
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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 |
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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
OX3 9DU
United Kingdom
Sponsor information
Hospital/treatment centre
Research and Development Office
Manor House
John Radcliffe Hospital
Oxford
OX3 9DU
England
United Kingdom
Phone | +44 (0)1865 222143 |
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emma.tucker@orh.nhs.uk | |
https://ror.org/03h2bh287 |
Funders
Funder type
Charity
No information available
Results and Publications
Intention to publish date | |
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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.