A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand

A CHENG, D Limmathurotaskul, W Chierakul, N Getchalarat, Vanaporn Wuthiekanun, D STEPHENS, N Day, N WHITE, W Chaowagul, Bart Currie, S PEACOCK

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background. Melioidosis is a tropical infectious disease associated with significant mortality. Most deaths occur early and are caused by fulminant sepsis. Methods. In this randomized, placebo-controlled trial, we assessed the efficacy of lenograstim (granulocyte colony-stimulating factor [G-CSF], 263 ?g per day administered intravenously) in ceftazidime-treated patients with severe sepsis caused by suspected melioidosis in Thailand. Results. Over a 27-month period, 60 patients were enrolled to receive either G-CSF (30 patients, 18 of whom had culture-confirmed melioidosis) or placebo (30 patients, 23 of whom had culture-confirmed melioidosis). Mortality rates were similar in both groups (G-CSF group, 70%; placebo group, 87%; risk ratio, 0.81; 95% confidence interval, 0.61-1.06; P = .2), including among patients with confirmed melioidosis (83% vs. 96%; P = .3). The duration of survival was longer for patients who received G-CSF than for patients who received placebo (33 h vs. 18.6 h; hazard ratio, 0.56; 95% confidence interval, 0.31-1.00; P = .05). Conclusions. Receipt of G-CSF is associated with a longer duration of survival but is not associated with a mortality benefit in patients with severe sepsis who are suspected of having melioidosis in Thailand. We hypothesize that G-CSF may "buy time" for severely septic patients, but survival is more likely to be improved by management of associated metabolic abnormalities and organ dysfunction associated with severe sepsis. � 2007 by the Infectious Diseases Society of America. All rights reserved.
    Original languageEnglish
    Pages (from-to)308-314
    Number of pages7
    JournalClinical Infectious Diseases
    Volume45
    Issue number3
    Publication statusPublished - 2007

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    Melioidosis
    Granulocyte Colony-Stimulating Factor
    Thailand
    Sepsis
    Randomized Controlled Trials
    Placebos
    Therapeutics
    Survival
    Mortality
    Confidence Intervals
    Ceftazidime
    Communicable Diseases
    Odds Ratio

    Cite this

    CHENG, A., Limmathurotaskul, D., Chierakul, W., Getchalarat, N., Wuthiekanun, V., STEPHENS, D., ... PEACOCK, S. (2007). A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clinical Infectious Diseases, 45(3), 308-314.
    CHENG, A ; Limmathurotaskul, D ; Chierakul, W ; Getchalarat, N ; Wuthiekanun, Vanaporn ; STEPHENS, D ; Day, N ; WHITE, N ; Chaowagul, W ; Currie, Bart ; PEACOCK, S. / A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. In: Clinical Infectious Diseases. 2007 ; Vol. 45, No. 3. pp. 308-314.
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    title = "A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand",
    abstract = "Background. Melioidosis is a tropical infectious disease associated with significant mortality. Most deaths occur early and are caused by fulminant sepsis. Methods. In this randomized, placebo-controlled trial, we assessed the efficacy of lenograstim (granulocyte colony-stimulating factor [G-CSF], 263 ?g per day administered intravenously) in ceftazidime-treated patients with severe sepsis caused by suspected melioidosis in Thailand. Results. Over a 27-month period, 60 patients were enrolled to receive either G-CSF (30 patients, 18 of whom had culture-confirmed melioidosis) or placebo (30 patients, 23 of whom had culture-confirmed melioidosis). Mortality rates were similar in both groups (G-CSF group, 70{\%}; placebo group, 87{\%}; risk ratio, 0.81; 95{\%} confidence interval, 0.61-1.06; P = .2), including among patients with confirmed melioidosis (83{\%} vs. 96{\%}; P = .3). The duration of survival was longer for patients who received G-CSF than for patients who received placebo (33 h vs. 18.6 h; hazard ratio, 0.56; 95{\%} confidence interval, 0.31-1.00; P = .05). Conclusions. Receipt of G-CSF is associated with a longer duration of survival but is not associated with a mortality benefit in patients with severe sepsis who are suspected of having melioidosis in Thailand. We hypothesize that G-CSF may {"}buy time{"} for severely septic patients, but survival is more likely to be improved by management of associated metabolic abnormalities and organ dysfunction associated with severe sepsis. � 2007 by the Infectious Diseases Society of America. All rights reserved.",
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    author = "A CHENG and D Limmathurotaskul and W Chierakul and N Getchalarat and Vanaporn Wuthiekanun and D STEPHENS and N Day and N WHITE and W Chaowagul and Bart Currie and S PEACOCK",
    year = "2007",
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    CHENG, A, Limmathurotaskul, D, Chierakul, W, Getchalarat, N, Wuthiekanun, V, STEPHENS, D, Day, N, WHITE, N, Chaowagul, W, Currie, B & PEACOCK, S 2007, 'A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand', Clinical Infectious Diseases, vol. 45, no. 3, pp. 308-314.

    A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. / CHENG, A; Limmathurotaskul, D; Chierakul, W; Getchalarat, N; Wuthiekanun, Vanaporn; STEPHENS, D; Day, N; WHITE, N; Chaowagul, W; Currie, Bart; PEACOCK, S.

    In: Clinical Infectious Diseases, Vol. 45, No. 3, 2007, p. 308-314.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand

    AU - CHENG, A

    AU - Limmathurotaskul, D

    AU - Chierakul, W

    AU - Getchalarat, N

    AU - Wuthiekanun, Vanaporn

    AU - STEPHENS, D

    AU - Day, N

    AU - WHITE, N

    AU - Chaowagul, W

    AU - Currie, Bart

    AU - PEACOCK, S

    PY - 2007

    Y1 - 2007

    N2 - Background. Melioidosis is a tropical infectious disease associated with significant mortality. Most deaths occur early and are caused by fulminant sepsis. Methods. In this randomized, placebo-controlled trial, we assessed the efficacy of lenograstim (granulocyte colony-stimulating factor [G-CSF], 263 ?g per day administered intravenously) in ceftazidime-treated patients with severe sepsis caused by suspected melioidosis in Thailand. Results. Over a 27-month period, 60 patients were enrolled to receive either G-CSF (30 patients, 18 of whom had culture-confirmed melioidosis) or placebo (30 patients, 23 of whom had culture-confirmed melioidosis). Mortality rates were similar in both groups (G-CSF group, 70%; placebo group, 87%; risk ratio, 0.81; 95% confidence interval, 0.61-1.06; P = .2), including among patients with confirmed melioidosis (83% vs. 96%; P = .3). The duration of survival was longer for patients who received G-CSF than for patients who received placebo (33 h vs. 18.6 h; hazard ratio, 0.56; 95% confidence interval, 0.31-1.00; P = .05). Conclusions. Receipt of G-CSF is associated with a longer duration of survival but is not associated with a mortality benefit in patients with severe sepsis who are suspected of having melioidosis in Thailand. We hypothesize that G-CSF may "buy time" for severely septic patients, but survival is more likely to be improved by management of associated metabolic abnormalities and organ dysfunction associated with severe sepsis. � 2007 by the Infectious Diseases Society of America. All rights reserved.

    AB - Background. Melioidosis is a tropical infectious disease associated with significant mortality. Most deaths occur early and are caused by fulminant sepsis. Methods. In this randomized, placebo-controlled trial, we assessed the efficacy of lenograstim (granulocyte colony-stimulating factor [G-CSF], 263 ?g per day administered intravenously) in ceftazidime-treated patients with severe sepsis caused by suspected melioidosis in Thailand. Results. Over a 27-month period, 60 patients were enrolled to receive either G-CSF (30 patients, 18 of whom had culture-confirmed melioidosis) or placebo (30 patients, 23 of whom had culture-confirmed melioidosis). Mortality rates were similar in both groups (G-CSF group, 70%; placebo group, 87%; risk ratio, 0.81; 95% confidence interval, 0.61-1.06; P = .2), including among patients with confirmed melioidosis (83% vs. 96%; P = .3). The duration of survival was longer for patients who received G-CSF than for patients who received placebo (33 h vs. 18.6 h; hazard ratio, 0.56; 95% confidence interval, 0.31-1.00; P = .05). Conclusions. Receipt of G-CSF is associated with a longer duration of survival but is not associated with a mortality benefit in patients with severe sepsis who are suspected of having melioidosis in Thailand. We hypothesize that G-CSF may "buy time" for severely septic patients, but survival is more likely to be improved by management of associated metabolic abnormalities and organ dysfunction associated with severe sepsis. � 2007 by the Infectious Diseases Society of America. All rights reserved.

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    KW - recombinant granulocyte colony stimulating factor

    KW - absence of side effects

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    KW - clinical article

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    KW - confidence interval

    KW - controlled clinical trial

    KW - controlled study

    KW - disease severity

    KW - drug efficacy

    KW - hazard ratio

    KW - human

    KW - melioidosis

    KW - metabolic disorder

    KW - mortality

    KW - multiple organ failure

    KW - priority journal

    KW - randomized controlled trial

    KW - sepsis

    KW - survival rate

    KW - survival time

    KW - Thailand

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    KW - APACHE

    KW - Granulocyte Colony-Stimulating Factor

    KW - Humans

    KW - Melioidosis

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    VL - 45

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    JO - Clinical Infectious Diseases

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    ER -

    CHENG A, Limmathurotaskul D, Chierakul W, Getchalarat N, Wuthiekanun V, STEPHENS D et al. A randomized controlled trial of granulocyte colony-stimulating factor for the treatment of severe sepsis due to melioidosis in Thailand. Clinical Infectious Diseases. 2007;45(3):308-314.