Rosuvastatin for sepsis-associated acute respiratory distress syndrome

Jonathon D. Truwit, Gordon R. Bernard, Jay Steingrub, Michael A. Matthay, Kathleen D. Liu, Timothy E Albertson, Roy G. Brower, Carl Shanholtz, Peter Rock, Ivor S. Douglas, Bennett P. DeBoisblanc, Catherine L. Hough, R. Duncan Hite, B. Taylor Thompson

Research output: Contribution to journalArticle

225 Citations (Scopus)

Abstract

BACKGROUND: In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS: We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14. RESULTS: The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P = 0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P = 0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P = 0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P = 0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS: Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.

Original languageEnglish (US)
Pages (from-to)2191-2200
Number of pages10
JournalNew England Journal of Medicine
Volume370
Issue number23
DOIs
StatePublished - 2014

Fingerprint

Adult Respiratory Distress Syndrome
Sepsis
Placebos
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mechanical Ventilators
Hospital Mortality
Medical Futility
Health Facilities
Liver Failure
Creatine Kinase
Rosuvastatin Calcium
Critical Illness
Multicenter Studies
Small Intestine
Observational Studies
Renal Insufficiency
Pneumonia
Oxidoreductases
Respiration
Reference Values

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Truwit, J. D., Bernard, G. R., Steingrub, J., Matthay, M. A., Liu, K. D., Albertson, T. E., ... Taylor Thompson, B. (2014). Rosuvastatin for sepsis-associated acute respiratory distress syndrome. New England Journal of Medicine, 370(23), 2191-2200. https://doi.org/10.1056/NEJMoa1401520

Rosuvastatin for sepsis-associated acute respiratory distress syndrome. / Truwit, Jonathon D.; Bernard, Gordon R.; Steingrub, Jay; Matthay, Michael A.; Liu, Kathleen D.; Albertson, Timothy E; Brower, Roy G.; Shanholtz, Carl; Rock, Peter; Douglas, Ivor S.; DeBoisblanc, Bennett P.; Hough, Catherine L.; Duncan Hite, R.; Taylor Thompson, B.

In: New England Journal of Medicine, Vol. 370, No. 23, 2014, p. 2191-2200.

Research output: Contribution to journalArticle

Truwit, JD, Bernard, GR, Steingrub, J, Matthay, MA, Liu, KD, Albertson, TE, Brower, RG, Shanholtz, C, Rock, P, Douglas, IS, DeBoisblanc, BP, Hough, CL, Duncan Hite, R & Taylor Thompson, B 2014, 'Rosuvastatin for sepsis-associated acute respiratory distress syndrome', New England Journal of Medicine, vol. 370, no. 23, pp. 2191-2200. https://doi.org/10.1056/NEJMoa1401520
Truwit, Jonathon D. ; Bernard, Gordon R. ; Steingrub, Jay ; Matthay, Michael A. ; Liu, Kathleen D. ; Albertson, Timothy E ; Brower, Roy G. ; Shanholtz, Carl ; Rock, Peter ; Douglas, Ivor S. ; DeBoisblanc, Bennett P. ; Hough, Catherine L. ; Duncan Hite, R. ; Taylor Thompson, B. / Rosuvastatin for sepsis-associated acute respiratory distress syndrome. In: New England Journal of Medicine. 2014 ; Vol. 370, No. 23. pp. 2191-2200.
@article{1e488a106f6d46b9bce4a18b993f79e5,
title = "Rosuvastatin for sepsis-associated acute respiratory distress syndrome",
abstract = "BACKGROUND: In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS: We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14. RESULTS: The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5{\%} with rosuvastatin and 24.9{\%} with placebo, P = 0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P = 0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P = 0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P = 0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS: Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.",
author = "Truwit, {Jonathon D.} and Bernard, {Gordon R.} and Jay Steingrub and Matthay, {Michael A.} and Liu, {Kathleen D.} and Albertson, {Timothy E} and Brower, {Roy G.} and Carl Shanholtz and Peter Rock and Douglas, {Ivor S.} and DeBoisblanc, {Bennett P.} and Hough, {Catherine L.} and {Duncan Hite}, R. and {Taylor Thompson}, B.",
year = "2014",
doi = "10.1056/NEJMoa1401520",
language = "English (US)",
volume = "370",
pages = "2191--2200",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "23",

}

TY - JOUR

T1 - Rosuvastatin for sepsis-associated acute respiratory distress syndrome

AU - Truwit, Jonathon D.

AU - Bernard, Gordon R.

AU - Steingrub, Jay

AU - Matthay, Michael A.

AU - Liu, Kathleen D.

AU - Albertson, Timothy E

AU - Brower, Roy G.

AU - Shanholtz, Carl

AU - Rock, Peter

AU - Douglas, Ivor S.

AU - DeBoisblanc, Bennett P.

AU - Hough, Catherine L.

AU - Duncan Hite, R.

AU - Taylor Thompson, B.

PY - 2014

Y1 - 2014

N2 - BACKGROUND: In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS: We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14. RESULTS: The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P = 0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P = 0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P = 0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P = 0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS: Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.

AB - BACKGROUND: In the acute respiratory distress syndrome (ARDS), inflammation in the lungs and other organs can cause life-threatening organ failure. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins) can modulate inflammatory responses. Previous observational studies suggested that statins improved clinical outcomes in patients with sepsis. We hypothesized that rosuvastatin therapy would improve clinical outcomes in critically ill patients with sepsis-associated ARDS. METHODS: We conducted a multicenter trial in which patients with sepsis-associated ARDS were randomly assigned to receive either enteral rosuvastatin or placebo in a double-blind manner. The primary outcome was mortality before hospital discharge home or until study day 60 if the patient was still in a health care facility. Secondary outcomes included the number of ventilator-free days (days that patients were alive and breathing spontaneously) to day 28 and organ-failure-free days to day 14. RESULTS: The study was stopped because of futility after 745 of an estimated 1000 patients had been enrolled. There was no significant difference between study groups in 60-day in-hospital mortality (28.5% with rosuvastatin and 24.9% with placebo, P = 0.21) or in mean (±SD) ventilator-free days (15.1±10.8 with rosuvastatin and 15.1±11.0 with placebo, P = 0.96). The groups were well matched with respect to demographic and key physiological variables. Rosuvastatin therapy, as compared with placebo, was associated with fewer days free of renal failure to day 14 (10.1±5.3 vs. 11.0±4.7, P = 0.01) and fewer days free of hepatic failure to day 14 (10.8±5.0 vs. 11.8±4.3, P = 0.003). Rosuvastatin was not associated with an increased incidence of serum creatine kinase levels that were more than 10 times the upper limit of the normal range. CONCLUSIONS: Rosuvastatin therapy did not improve clinical outcomes in patients with sepsis-associated ARDS and may have contributed to hepatic and renal organ dysfunction.

UR - http://www.scopus.com/inward/record.url?scp=84901759539&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901759539&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1401520

DO - 10.1056/NEJMoa1401520

M3 - Article

C2 - 24835849

AN - SCOPUS:84901759539

VL - 370

SP - 2191

EP - 2200

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 23

ER -