title: Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial).
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  International Standard Randomized Control Trial Registry ISRCTN64637517.
authors.forename: Jaimin M
authors.initials: JM
authors.lastname: Patel
authors.forename: Catherine
authors.initials: C
authors.lastname: Snaith
authors.forename: David R
authors.initials: DR
authors.lastname: Thickett
authors.forename: Lucie
authors.initials: L
authors.lastname: Linhartova
authors.forename: Teresa
authors.initials: T
authors.lastname: Melody
authors.forename: Peter
authors.initials: P
authors.lastname: Hawkey
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Barnett
authors.forename: Alan
authors.initials: A
authors.lastname: Jones
authors.forename: Tan
authors.initials: T
authors.lastname: Hong
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Cooke
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Perkins
authors.forename: Fang
authors.initials: F
authors.lastname: Gao
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069059:Atorvastatin; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission / Q000706:statistics & numerical data; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin