Statins for the Early Treatment of Sepsis

Study Overview
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Brief Summary
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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.

Official Title
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Statins for the Early Treatment of Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Identical-appearing placebo


Participation Criteria
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Eligibility Criteria
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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) Clinically suspected infection as per the treating physician or confirmed infection 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Simvastatin 80 mg once daily PO (or via NG or G-tube) | Drug: Simvastatin<br>* 80 mg once daily PO/NG x 4 days<br>|
| Placebo Comparator: 2<br>Identical-appearing placebo PO (or via NG or G-tube) | Drug: Identical-appearing placebo<br>* once daily x 4 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Statin, Infection, Immunomodulatory