None listed
Conditions
Brief summary
Background: 15,000 people are admitted to an Intensive Care Unit in Australia with severe sepsis every year. One third of these patients will die. Severe sepsis occurs when an infection causes dysfunction of one or more of the major organs (such as the heart or kidneys). A significant factor in this illness is that the body's normal response to infection or'inflammatory response' becomes abnormal. The statins are a class of medications commonly used in Australia to lower cholesterol. Previous research suggests that they may also have a beneficial effect on inflammation and that it may be harmful for people who are already taking statins to stop taking them if they develop severe sepsis. There is a lack of current information on the effects of these drugs in acute illness and the risks and benefits of continuing or starting treatment with them in patients with severe sepsis in the ICU. The aims of this project are: To assess the safety profile of atorvastatin in patients with severe sepsis To assess the effect of atorvastatin on inflammation and the outcome of patients with severe sepsis Research Design: A randomised controlled trial of atorvastatin 20mg versus placebo. Methods: Patients in the ICU with severe sepsis who meet the entry criteria will be given 20 mg of atorvastatin (a commerically available medication) or a placebo ("dummy drug"). The study drug will be given as a capsule by mouth or the contents will be given mixed with water via a feeding tube. Drug will be given once per day while the patient is in the ICU to a maximum of 28 days. Safety blood tests to look for signs of liver or muscle damage will be taken every day. Additional blood tests to assess inflammation will be taken 6 times during the study. All other care will be given as standard care.
Interventions
Randomised allocation of oral or enteral atorvastatin 20mg given daily to a maximum of 28 days (or until discharge from the intensive care unit)
Sponsors
Australia New Zealand Intensive Care Research Centre, a centre of Monash University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
All patients admitted to the intensive care unit with severe sepsis of less than 24 hours duration. Patients must have 3 or more features of systemic inflammatory response syndrome, a strongly suspected or confirmed site of sepsis, presence of organ dysfunction in at least one of the 5 following categories: (cardiovascular system , renal, respiratory, haematologic, unexplained metabolic acidosis).
Exclusion criteria
Death is imminent, pregnancy or breastfeeding, known history of intolerance to a statin agent, acute liver failure (INR[International Normalised Ratio] greater than 2.5), Child's C classification of liver disease ( a grade of C as measured on the Child-Pugh Classification of Liver Disease, ie very severe liver disease), ALT (alanine transaminase ) > 5 x ULN (Upper Limit of Normal), CK (creatinine kinase) > 5x ULN (Upper Limit of Normal), patient unable to take enteral medication, patient or next of kin/person responsible unable to provide informed consent, patient, family or physician not in favor of aggressive treatment.
Outcome results
None listed