Statins for the Early Treatment of Sepsis

Sepsis Clinical Trial

— SETS  

Official title:

Statins for the Early Treatment of Sepsis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00528580
• Other study ID #: 15420A
• Status: Terminated
• Phase: Phase 2
• Start date: February 2008
• Est. completion date: September 2011

Study information

• Verified date: August 2018
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Drug:
• Simvastatin
80 mg once daily PO/NG x 4 days
• Identical-appearing placebo
once daily x 4 days

Locations

Country	Name	City	State
United States	The University of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

References & Publications (16)

Almog Y, Shefer A, Novack V, Maimon N, Barski L, Eizinger M, Friger M, Zeller L, Danon A. Prior statin therapy is associated with a decreased rate of severe sepsis. Circulation. 2004 Aug 17;110(7):880-5. Epub 2004 Aug 2. — View Citation

American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992 Jun;20(6):864-74. Review. — View Citation

Dunbar LM, Wunderink RG, Habib MP, Smith LG, Tennenberg AM, Khashab MM, Wiesinger BA, Xiang JX, Zadeikis N, Kahn JB. High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis. 2003 Sep 15;37(6):752-60. Epub 2003 Aug 28. Erratum in: Clin Infect Dis. 2003 Oct 15;37(8):1147. — View Citation

Greenwood J, Walters CE, Pryce G, Kanuga N, Beraud E, Baker D, Adamson P. Lovastatin inhibits brain endothelial cell Rho-mediated lymphocyte migration and attenuates experimental autoimmune encephalomyelitis. FASEB J. 2003 May;17(8):905-7. doi: 10.1096/fj.02-1014fje. Epub 2003 Mar 5. — View Citation

Gupta R, Plantinga LC, Fink NE, Melamed ML, Coresh J, Fox CS, Levin NW, Powe NR. Statin use and sepsis events [corrected] in patients with chronic kidney disease. JAMA. 2007 Apr 4;297(13):1455-64. Erratum in: JAMA. 2008 Feb 20;299(7):765. — View Citation

Hackam DG, Mamdani M, Li P, Redelmeier DA. Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet. 2006 Feb 4;367(9508):413-8. — View Citation

Jacobson JR, Barnard JW, Grigoryev DN, Ma SF, Tuder RM, Garcia JG. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol. 2005 Jun;288(6):L1026-32. Epub 2005 Jan 21. — View Citation

Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H, Madhok R, Campbell C, Gracie JA, Liew FY, McInnes IB. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol. 2003 Feb 1;170(3):1524-30. — View Citation

Liappis AP, Kan VL, Rochester CG, Simon GL. The effect of statins on mortality in patients with bacteremia. Clin Infect Dis. 2001 Oct 15;33(8):1352-7. Epub 2001 Sep 20. — View Citation

Majumdar SR, McAlister FA, Eurich DT, Padwal RS, Marrie TJ. Statins and outcomes in patients admitted to hospital with community acquired pneumonia: population based prospective cohort study. BMJ. 2006 Nov 11;333(7576):999. Epub 2006 Oct 23. — View Citation

Merx MW, Liehn EA, Graf J, van de Sandt A, Schaltenbrand M, Schrader J, Hanrath P, Weber C. Statin treatment after onset of sepsis in a murine model improves survival. Circulation. 2005 Jul 5;112(1):117-24. — View Citation

Naidu BV, Woolley SM, Farivar AS, Thomas R, Fraga C, Mulligan MS. Simvastatin ameliorates injury in an experimental model of lung ischemia-reperfusion. J Thorac Cardiovasc Surg. 2003 Aug;126(2):482-9. — View Citation

Oba Y, Salzman GA. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury. N Engl J Med. 2000 Sep 14;343(11):813; author reply 813-4. — View Citation

Schmidt H, Hennen R, Keller A, Russ M, Müller-Werdan U, Werdan K, Buerke M. Association of statin therapy and increased survival in patients with multiple organ dysfunction syndrome. Intensive Care Med. 2006 Aug;32(8):1248-51. Epub 2006 Jun 21. — View Citation

Thomsen RW, Hundborg HH, Johnsen SP, Pedersen L, Sørensen HT, Schønheyder HC, Lervang HH. Statin use and mortality within 180 days after bacteremia: a population-based cohort study. Crit Care Med. 2006 Apr;34(4):1080-6. — View Citation

Yasuda H, Yuen PS, Hu X, Zhou H, Star RA. Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects. Kidney Int. 2006 May;69(9):1535-42. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	24 hours