Sepsis
Conditions
Keywords
Sepsis, Statin, Infection, Immunomodulatory
Brief summary
We propose a Phase II, randomized, placebo-controlled clinical trial to test the hypothesis that treatment with once-daily statins has a beneficial effect on inflammatory cytokines and clinical outcomes in adults hospitalized with sepsis. As our animal models suggest pretreatment with statins are required for their beneficial effects, we propose a study design intended to identify patients and initiate treatment early in their hospital stay. This Phase II study is intended to assess the feasibility of conducting a large-scale investigator-initiated translational research protocol that involves multiple clinical services within the Department of Medicine.
Interventions
DRUGSimvastatin
80 mg once daily PO/NG x 4 days
once daily x 4 days
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Initial presentation to the Emergency Department or University of Chicago MD office/Dialysis Center for current hospital admission * Sepsis (ACCP/SCCM criteria) 1. Clinically suspected infection as per the treating physician or confirmed infection 2. 2 or more of the following: Temperature 38ºC (100.4ºF)or 36ºC (96.8ºF), Heart rate (HR) \> 90/min, Respiratory rate (RR) \> 20/min or PaCO2 \< 32 mmHg, White blood cell count \> 12,000/mm3 or \< 4000/m3 or \> 10%immature neutrophils * Initiation of antibiotics by treating physician for sepsis * Hospitalized from the Emergency Department or University of Chicago MD office/Dialysis Center to an inpatient medical service (intensive care unit (ICU)or non-ICU service) OR admission to the medical ICU (MICU) from a non-ICU inpatient medical floor. * Assent of the primary treating physician at the time of enrollment. * The meeting of SIRS criteria is due to an infection as per the treating physician.
Exclusion criteria
* Pregnancy * ALT \>3 times above the upper limit of normal * Elevated creatine phosphokinase (CPK) (\>3 times the upper limit of normal) * Concurrent treatment with any of the following drugs: daptomycin, fenofibrate, ketoconazole,triaconazole, amiodarone, clarithromycin, cyclosporine, erythromycin,nefazodone, niacin, protease inhibitors, telithromycin, verapamil,danazol, gemfibrozil * History of allergy or intolerance to statins * Greater than 16 hours after meeting inclusion criteria * Use of 1 more doses of statins in the previous 4 weeks * Clinical indication for treatment with statin during hospital admission (per treating physician) * Sufficiently poor prognosis prior to enrollment that treating physicians have elected to employ comfort care or plan to discharge to hospice * Transfer from surgical service to medical service * Needing transfusion for either active bleeding or severe hemolysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Clinical Stability | 24 hours | Normalization of vital signs for each subject enrolled. This is expressed as a mean time to normalization for each +/- standard error. |
Countries
United States
Participant flow
Recruitment details
Patients enrolled 2008-2009 at University of Chicago and Mercy Hosptial in Chicago, IL
Participants by arm
| Arm | Count |
|---|---|
| Experimental Simvastatin 80 mg once daily PO (or via NG or G-tube)
Simvastatin: 80 mg once daily PO/NG x 4 days | 34 |
| Placebo Identical-appearing placebo PO (or via NG or G-tube)
Identical-appearing placebo: once daily x 4 days | 34 |
| Total | 68 |
Baseline characteristics
| Characteristic | Experimental | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants | 34 Participants | 68 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 8 | 52 years STANDARD_DEVIATION 8 | 52 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 34 Participants | 34 Participants | 68 Participants |
| Sex: Female, Male Female | 17 Participants | 17 Participants | 34 Participants |
| Sex: Female, Male Male | 17 Participants | 17 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 0 / 34 |
| serious Total, serious adverse events | 0 / 34 | 0 / 34 |
Outcome results
Primary
Time to Clinical Stability
Normalization of vital signs for each subject enrolled. This is expressed as a mean time to normalization for each +/- standard error.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Group | Time to Clinical Stability | 3 days | Standard Error 1 |
| Control Group | Time to Clinical Stability | 3 days | Standard Error 1 |