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Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial)

Jaimin M Patel1, Catherine Snaith1, David R Thickett2, Lucie Linhartova1, Teresa Melody1, Peter Hawkey34, Anthony H Barnett5, Alan Jones6, Tan Hong1, Matthew W Cooke78, Gavin D Perkins19 and Fang Gao1*

Author Affiliations

1 Academic Department of Anaesthesia, Pain and Critical Care, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, B9 5SS, UK

2 School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

3 Department of Public Health and Bacteriology, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

4 Department of Microbiology, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, B9 5SS, UK

5 Diabetes Centre, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, B9 5SS, UK

6 Department of Pathology, Heart of England NHS Foundation Trust, Bordesley Green East, Birmingham, B9 5SS UK

7 Health Sciences, Medical School Building, Gibbet Hill Campus, University of Warwick, Coventry, CV4 7AL, UK

8 Department of Accident & Emergency, Heart of England NHS Foundation Trust, Bordesley Green, Birmingham, B9 5SS, UK

9 Clinical Trials Unit, Warwick Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK

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Critical Care 2012, 16:R231  doi:10.1186/cc11895

Published: 11 December 2012

Abstract

Introduction

Several observational studies suggest that statins modulate the pathophysiology of sepsis and may prevent its progression. The aim of this study was to determine if the acute administration of atorvastatin reduces sepsis progression in statin naïve patients hospitalized with sepsis.

Methods

A single centre phase II randomized double-blind placebo-controlled trial. Patients with sepsis were randomized to atorvastatin 40 mg daily or placebo for the duration of their hospital stay up to a maximum of 28-days. The primary end-point was the rate of sepsis progressing to severe sepsis during hospitalization.

Results

100 patients were randomized, 49 to the treatment with atorvastatin and 51 to placebo. Patients in the atorvastatin group had a significantly lower conversion rate to severe sepsis compared to placebo (4% vs. 24% p = 0.007.), with a number needed to treat of 5. No significant difference in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality was observed. Plasma cholesterol and albumin creatinine ratios were significantly lower at day 4 in the atorvastatin group (p < 0.0001 and p = 0.049 respectively). No difference in adverse events between the two groups was observed (p = 0.238).

Conclusions

Acute administration of atorvastatin in patients with sepsis may prevent sepsis progression. Further multi-centre trials are required to verify these findings.

Trial Registration

International Standard Randomized Control Trial Registry ISRCTN64637517.