Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock

D STEPHENS, Jane Thomas, L Higgins, Mark Bailey, Nicholas Anstey, Bart Currie, Allen Cheng

Research output: Contribution to journalArticleResearchpeer-review

Abstract

OBJECTIVE: To investigate the effect of early administration of granulocyte colony-stimulating factor (G-CSF) on hospital mortality in nonneutropenic patients with septic shock, excluding patients with melioidosis. DESIGN: A randomized, placebo-controlled, double-blinded clinical trial. SETTING AND PATIENTS: Adult patients with septic shock admitted to the Royal Darwin Hospital Intensive Care Unit. INTERVENTIONS: Patients were randomized to receive G-CSF or placebo intravenously daily for 10 days, in addition to routine management of septic shock. MEASUREMENTS: Primary outcome was hospital mortality. Secondary outcomes included intensive care unit mortality, intensive care unit and hospital length of stay, ventilator hours, and time to resolution of shock. Patient comorbidities, baseline and daily physiology, and organ function were collected. RESULTS: Of 166 patients enrolled, 83 were allocated to receive G-CSF (81 included in analysis) and 83 were allocated to receive placebo. At baseline, 30% of patients had diabetes, 18% were known to have renal impairment or failure, and 38% had a history of hazardous alcohol use. The two groups had similar comorbidities at baseline and a similar severity of illness. The in-hospital mortality was 27% in the G-CSF group and 25% in the placebo group. Secondary end points were not different between groups. There was a higher rate of new organ failure in G-CSF-treated patients than placebo-treated patients (50% vs. 33%, p = .03), most of which was accounted for by new liver dysfunction (11% vs. 1%, p = .007). There was no significant difference in the proportion of patients with troponin I of >0.08 mg/L (78% vs. 66%, p = .09), and the prevalence of acute myocardial infarction (6% vs. 4%, p = .55) was not different during the study. The median peak troponin I level was higher in the G-CSF group (0.5 vs. 0.14 mg/L, p = .007), but baseline levels were not available. CONCLUSION: G-CSF does not improve outcomes in patients with septic shock, excluding melioidosis. Increased hepatic dysfunction and higher peak troponin levels in patients receiving G-CSF have not been reported in previous clinical trials and warrant further investigation. � 2008 Lippincott Williams & Wilkins, Inc.
Original languageEnglish
Pages (from-to)448-454
Number of pages7
JournalCritical Care Medicine
Volume36
Issue number2
Publication statusPublished - 2008

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Granulocyte Colony-Stimulating Factor
Septic Shock
Placebos
Hospital Mortality
Melioidosis
Intensive Care Units
Troponin I
Comorbidity
Length of Stay
Clinical Trials
Troponin
Mechanical Ventilators
Liver Diseases
Shock
Myocardial Infarction
Alcohols
Kidney

Cite this

@article{1cbd7a9f700043b485b0d8ed0d4f9848,
title = "Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock",
abstract = "OBJECTIVE: To investigate the effect of early administration of granulocyte colony-stimulating factor (G-CSF) on hospital mortality in nonneutropenic patients with septic shock, excluding patients with melioidosis. DESIGN: A randomized, placebo-controlled, double-blinded clinical trial. SETTING AND PATIENTS: Adult patients with septic shock admitted to the Royal Darwin Hospital Intensive Care Unit. INTERVENTIONS: Patients were randomized to receive G-CSF or placebo intravenously daily for 10 days, in addition to routine management of septic shock. MEASUREMENTS: Primary outcome was hospital mortality. Secondary outcomes included intensive care unit mortality, intensive care unit and hospital length of stay, ventilator hours, and time to resolution of shock. Patient comorbidities, baseline and daily physiology, and organ function were collected. RESULTS: Of 166 patients enrolled, 83 were allocated to receive G-CSF (81 included in analysis) and 83 were allocated to receive placebo. At baseline, 30{\%} of patients had diabetes, 18{\%} were known to have renal impairment or failure, and 38{\%} had a history of hazardous alcohol use. The two groups had similar comorbidities at baseline and a similar severity of illness. The in-hospital mortality was 27{\%} in the G-CSF group and 25{\%} in the placebo group. Secondary end points were not different between groups. There was a higher rate of new organ failure in G-CSF-treated patients than placebo-treated patients (50{\%} vs. 33{\%}, p = .03), most of which was accounted for by new liver dysfunction (11{\%} vs. 1{\%}, p = .007). There was no significant difference in the proportion of patients with troponin I of >0.08 mg/L (78{\%} vs. 66{\%}, p = .09), and the prevalence of acute myocardial infarction (6{\%} vs. 4{\%}, p = .55) was not different during the study. The median peak troponin I level was higher in the G-CSF group (0.5 vs. 0.14 mg/L, p = .007), but baseline levels were not available. CONCLUSION: G-CSF does not improve outcomes in patients with septic shock, excluding melioidosis. Increased hepatic dysfunction and higher peak troponin levels in patients receiving G-CSF have not been reported in previous clinical trials and warrant further investigation. � 2008 Lippincott Williams & Wilkins, Inc.",
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author = "D STEPHENS and Jane Thomas and L Higgins and Mark Bailey and Nicholas Anstey and Bart Currie and Allen Cheng",
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Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock. / STEPHENS, D; Thomas, Jane; Higgins, L; Bailey, Mark; Anstey, Nicholas; Currie, Bart; Cheng, Allen.

In: Critical Care Medicine, Vol. 36, No. 2, 2008, p. 448-454.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor in patients with septic shock

AU - STEPHENS, D

AU - Thomas, Jane

AU - Higgins, L

AU - Bailey, Mark

AU - Anstey, Nicholas

AU - Currie, Bart

AU - Cheng, Allen

PY - 2008

Y1 - 2008

N2 - OBJECTIVE: To investigate the effect of early administration of granulocyte colony-stimulating factor (G-CSF) on hospital mortality in nonneutropenic patients with septic shock, excluding patients with melioidosis. DESIGN: A randomized, placebo-controlled, double-blinded clinical trial. SETTING AND PATIENTS: Adult patients with septic shock admitted to the Royal Darwin Hospital Intensive Care Unit. INTERVENTIONS: Patients were randomized to receive G-CSF or placebo intravenously daily for 10 days, in addition to routine management of septic shock. MEASUREMENTS: Primary outcome was hospital mortality. Secondary outcomes included intensive care unit mortality, intensive care unit and hospital length of stay, ventilator hours, and time to resolution of shock. Patient comorbidities, baseline and daily physiology, and organ function were collected. RESULTS: Of 166 patients enrolled, 83 were allocated to receive G-CSF (81 included in analysis) and 83 were allocated to receive placebo. At baseline, 30% of patients had diabetes, 18% were known to have renal impairment or failure, and 38% had a history of hazardous alcohol use. The two groups had similar comorbidities at baseline and a similar severity of illness. The in-hospital mortality was 27% in the G-CSF group and 25% in the placebo group. Secondary end points were not different between groups. There was a higher rate of new organ failure in G-CSF-treated patients than placebo-treated patients (50% vs. 33%, p = .03), most of which was accounted for by new liver dysfunction (11% vs. 1%, p = .007). There was no significant difference in the proportion of patients with troponin I of >0.08 mg/L (78% vs. 66%, p = .09), and the prevalence of acute myocardial infarction (6% vs. 4%, p = .55) was not different during the study. The median peak troponin I level was higher in the G-CSF group (0.5 vs. 0.14 mg/L, p = .007), but baseline levels were not available. CONCLUSION: G-CSF does not improve outcomes in patients with septic shock, excluding melioidosis. Increased hepatic dysfunction and higher peak troponin levels in patients receiving G-CSF have not been reported in previous clinical trials and warrant further investigation. � 2008 Lippincott Williams & Wilkins, Inc.

AB - OBJECTIVE: To investigate the effect of early administration of granulocyte colony-stimulating factor (G-CSF) on hospital mortality in nonneutropenic patients with septic shock, excluding patients with melioidosis. DESIGN: A randomized, placebo-controlled, double-blinded clinical trial. SETTING AND PATIENTS: Adult patients with septic shock admitted to the Royal Darwin Hospital Intensive Care Unit. INTERVENTIONS: Patients were randomized to receive G-CSF or placebo intravenously daily for 10 days, in addition to routine management of septic shock. MEASUREMENTS: Primary outcome was hospital mortality. Secondary outcomes included intensive care unit mortality, intensive care unit and hospital length of stay, ventilator hours, and time to resolution of shock. Patient comorbidities, baseline and daily physiology, and organ function were collected. RESULTS: Of 166 patients enrolled, 83 were allocated to receive G-CSF (81 included in analysis) and 83 were allocated to receive placebo. At baseline, 30% of patients had diabetes, 18% were known to have renal impairment or failure, and 38% had a history of hazardous alcohol use. The two groups had similar comorbidities at baseline and a similar severity of illness. The in-hospital mortality was 27% in the G-CSF group and 25% in the placebo group. Secondary end points were not different between groups. There was a higher rate of new organ failure in G-CSF-treated patients than placebo-treated patients (50% vs. 33%, p = .03), most of which was accounted for by new liver dysfunction (11% vs. 1%, p = .007). There was no significant difference in the proportion of patients with troponin I of >0.08 mg/L (78% vs. 66%, p = .09), and the prevalence of acute myocardial infarction (6% vs. 4%, p = .55) was not different during the study. The median peak troponin I level was higher in the G-CSF group (0.5 vs. 0.14 mg/L, p = .007), but baseline levels were not available. CONCLUSION: G-CSF does not improve outcomes in patients with septic shock, excluding melioidosis. Increased hepatic dysfunction and higher peak troponin levels in patients receiving G-CSF have not been reported in previous clinical trials and warrant further investigation. � 2008 Lippincott Williams & Wilkins, Inc.

KW - azithromycin

KW - meropenem

KW - piperacillin plus tazobactam

KW - placebo

KW - recombinant granulocyte colony stimulating factor

KW - troponin I

KW - acute heart infarction

KW - adult

KW - article

KW - artificial ventilation

KW - clinical trial

KW - comorbidity

KW - controlled clinical trial

KW - controlled study

KW - diabetes mellitus

KW - disease severity

KW - double blind procedure

KW - female

KW - hospital admission

KW - hospitalization

KW - human

KW - intensive care unit

KW - kidney failure

KW - length of stay

KW - liver dysfunction

KW - major clinical study

KW - male

KW - mortality

KW - priority journal

KW - randomized controlled trial

KW - septic shock

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KW - Aged

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KW - Drug Administration Schedule

KW - Female

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KW - Hospital Mortality

KW - Humans

KW - Intensive Care

KW - Length of Stay

KW - Male

KW - Middle Aged

KW - Recombinant Proteins

KW - Shock, Septic

KW - Treatment Outcome

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