Statins for the Early Treatment of Sepsis

NCT ID: NCT00528580

Last Updated: 2018-09-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-29

Study Completion Date

2011-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Sepsis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

Simvastatin 80 mg once daily PO (or via NG or G-tube)

Group Type EXPERIMENTAL

Simvastatin

Intervention Type DRUG

80 mg once daily PO/NG x 4 days

2

Identical-appearing placebo PO (or via NG or G-tube)

Group Type PLACEBO_COMPARATOR

Identical-appearing placebo

Intervention Type DRUG

once daily x 4 days

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Simvastatin

80 mg once daily PO/NG x 4 days

Intervention Type DRUG

Identical-appearing placebo

once daily x 4 days

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

* 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.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Chicago

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jerry Krishnan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

The University of Chicago

Chicago, Illinois, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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. No abstract available.

Reference Type BACKGROUND
PMID: 10991706 (View on PubMed)

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. doi: 10.1161/01.CIR.0000138932.17956.F1. Epub 2004 Aug 2.

Reference Type BACKGROUND
PMID: 15289367 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1597042 (View on PubMed)

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. doi: 10.1086/377539. Epub 2003 Aug 28.

Reference Type BACKGROUND
PMID: 12955634 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12626426 (View on PubMed)

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. doi: 10.1001/jama.297.13.1455.

Reference Type BACKGROUND
PMID: 17405971 (View on PubMed)

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. doi: 10.1016/S0140-6736(06)68041-0.

Reference Type BACKGROUND
PMID: 16458766 (View on PubMed)

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. doi: 10.1152/ajplung.00354.2004. Epub 2005 Jan 21.

Reference Type BACKGROUND
PMID: 15665042 (View on PubMed)

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. doi: 10.4049/jimmunol.170.3.1524.

Reference Type BACKGROUND
PMID: 12538717 (View on PubMed)

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. doi: 10.1086/323334. Epub 2001 Sep 20.

Reference Type BACKGROUND
PMID: 11565076 (View on PubMed)

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. doi: 10.1136/bmj.38992.565972.7C. Epub 2006 Oct 23.

Reference Type BACKGROUND
PMID: 17060337 (View on PubMed)

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. doi: 10.1161/CIRCULATIONAHA.104.502195.

Reference Type BACKGROUND
PMID: 15998696 (View on PubMed)

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. doi: 10.1016/s0022-5223(03)00699-8.

Reference Type BACKGROUND
PMID: 12928648 (View on PubMed)

Schmidt H, Hennen R, Keller A, Russ M, Muller-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. doi: 10.1007/s00134-006-0246-y. Epub 2006 Jun 21.

Reference Type BACKGROUND
PMID: 16788803 (View on PubMed)

Thomsen RW, Hundborg HH, Johnsen SP, Pedersen L, Sorensen HT, Schonheyder 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. doi: 10.1097/01.CCM.0000207345.92928.E4.

Reference Type BACKGROUND
PMID: 16484926 (View on PubMed)

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. doi: 10.1038/sj.ki.5000300.

Reference Type BACKGROUND
PMID: 16557230 (View on PubMed)

Dobesh PP, Olsen KM. Statins role in the prevention and treatment of sepsis. Pharmacol Res. 2014 Oct;88:31-40. doi: 10.1016/j.phrs.2014.04.010. Epub 2014 May 2.

Reference Type DERIVED
PMID: 24794878 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

15420A

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

LIPIDS-P Trial Phase I/II Trial
NCT03405870 COMPLETED PHASE1/PHASE2
Comparison of Sepsis Prediction Algorithms
NCT05943938 NOT_YET_RECRUITING