Statins for the Early Treatment of Sepsis
Condition: Sepsis
MeSH terms: Sepsis; Toxemia
Intervention: Simvastatin; Identical-appearing placebo
Intervention description: 80 mg once daily PO/NG x 4 days; once daily x 4 days
Intervention MeSH terms: Simvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 68.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Sepsis; Statin; Infection; Immunomodulatory

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.
    

Eligibility criteria:

        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.