A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis: BLING III

Jeffrey Lipman, Stephen J. Brett, Jan J. De Waele, Menino O. Cotta, Joshua S. Davis, Simon Finfer, Parisa Glass, Serena Knowles, Shay McGuinness, John Myburgh, David L. Paterson, Sandra Peake, Dorrilyn Rajbhandari, Andrew Rhodes, Jason A. Roberts, Charudatt Shirwadkar, Therese Starr, Colman Taylor, Laurent Billot, Joel M. Dulhunty

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background and Rationale: β-Lactam antibiotics display a time-dependent mechanism of action, with evidence suggesting improved outcomes when administering these drugs via continuous infusion compared with standard intermittent infusion. However, there is no phase 3 randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis.

Design and Setting: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 RCT to compare continuous infusion with standard intermittent infusion of β-lactam antibiotics in critically ill patients with sepsis. The study will be conducted in about 70 intensive care units (ICUs) in Australia, New Zealand, the United Kingdom, Belgium and selected other countries, from 2018 to 2021.

Participants and Interventions: BLING III will recruit 7000 critically ill patients with sepsis being treated with one of two β-lactam antibiotics (piperacillin-tazobactam or meropenem) to receive the β-lactam antibiotic by either continuous or intermittent infusion.

Main Outcome Measures: The primary outcome is allcause mortality within 90 days after randomisation. Secondary outcomes are clinical cure at Day 14 after randomisation, new acquisition, colonisation or infection with a multiresistant organism or Clostridium difficile diarrhoea up to 14 days after randomisation, all-cause ICU mortality and all-cause hospital mortality. Tertiary outcomes are ICU length of stay, hospital length of stay and duration of mechanical ventilation and duration of renal replacement therapy up to 90 days after randomisation.

Results and Conclusions: The BLING III study will compare the effect on 90-day mortality of β-lactam antibiotics administered via continuous versus intermittent infusion in 7000 critically ill patients with sepsis.

Trial Registration: ClinicalTrials.gov Registry (NCT03213990).

Original languageEnglish
Pages (from-to)63-68
Number of pages6
JournalCritical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine
Volume21
Issue number1
Publication statusPublished - 1 Mar 2019

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Lactams
Critical Illness
Sepsis
Randomized Controlled Trials
Random Allocation
Anti-Bacterial Agents
Intensive Care Units
Length of Stay
meropenem
Mortality
Renal Replacement Therapy
Clostridium difficile
Belgium
Hospital Mortality
New Zealand
Artificial Respiration
Registries
Diarrhea
Outcome Assessment (Health Care)
Infection

Cite this

Lipman, Jeffrey ; Brett, Stephen J. ; De Waele, Jan J. ; Cotta, Menino O. ; Davis, Joshua S. ; Finfer, Simon ; Glass, Parisa ; Knowles, Serena ; McGuinness, Shay ; Myburgh, John ; Paterson, David L. ; Peake, Sandra ; Rajbhandari, Dorrilyn ; Rhodes, Andrew ; Roberts, Jason A. ; Shirwadkar, Charudatt ; Starr, Therese ; Taylor, Colman ; Billot, Laurent ; Dulhunty, Joel M. / A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis : BLING III. In: Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine. 2019 ; Vol. 21, No. 1. pp. 63-68.
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title = "A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis: BLING III",
abstract = "Background and Rationale: β-Lactam antibiotics display a time-dependent mechanism of action, with evidence suggesting improved outcomes when administering these drugs via continuous infusion compared with standard intermittent infusion. However, there is no phase 3 randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis. Design and Setting: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 RCT to compare continuous infusion with standard intermittent infusion of β-lactam antibiotics in critically ill patients with sepsis. The study will be conducted in about 70 intensive care units (ICUs) in Australia, New Zealand, the United Kingdom, Belgium and selected other countries, from 2018 to 2021. Participants and Interventions: BLING III will recruit 7000 critically ill patients with sepsis being treated with one of two β-lactam antibiotics (piperacillin-tazobactam or meropenem) to receive the β-lactam antibiotic by either continuous or intermittent infusion. Main Outcome Measures: The primary outcome is allcause mortality within 90 days after randomisation. Secondary outcomes are clinical cure at Day 14 after randomisation, new acquisition, colonisation or infection with a multiresistant organism or Clostridium difficile diarrhoea up to 14 days after randomisation, all-cause ICU mortality and all-cause hospital mortality. Tertiary outcomes are ICU length of stay, hospital length of stay and duration of mechanical ventilation and duration of renal replacement therapy up to 90 days after randomisation. Results and Conclusions: The BLING III study will compare the effect on 90-day mortality of β-lactam antibiotics administered via continuous versus intermittent infusion in 7000 critically ill patients with sepsis. Trial Registration: ClinicalTrials.gov Registry (NCT03213990).",
author = "Jeffrey Lipman and Brett, {Stephen J.} and {De Waele}, {Jan J.} and Cotta, {Menino O.} and Davis, {Joshua S.} and Simon Finfer and Parisa Glass and Serena Knowles and Shay McGuinness and John Myburgh and Paterson, {David L.} and Sandra Peake and Dorrilyn Rajbhandari and Andrew Rhodes and Roberts, {Jason A.} and Charudatt Shirwadkar and Therese Starr and Colman Taylor and Laurent Billot and Dulhunty, {Joel M.}",
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Lipman, J, Brett, SJ, De Waele, JJ, Cotta, MO, Davis, JS, Finfer, S, Glass, P, Knowles, S, McGuinness, S, Myburgh, J, Paterson, DL, Peake, S, Rajbhandari, D, Rhodes, A, Roberts, JA, Shirwadkar, C, Starr, T, Taylor, C, Billot, L & Dulhunty, JM 2019, 'A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis: BLING III' Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine, vol. 21, no. 1, pp. 63-68.

A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis : BLING III. / Lipman, Jeffrey; Brett, Stephen J.; De Waele, Jan J.; Cotta, Menino O.; Davis, Joshua S.; Finfer, Simon; Glass, Parisa; Knowles, Serena; McGuinness, Shay; Myburgh, John; Paterson, David L.; Peake, Sandra; Rajbhandari, Dorrilyn; Rhodes, Andrew; Roberts, Jason A.; Shirwadkar, Charudatt; Starr, Therese; Taylor, Colman; Billot, Laurent; Dulhunty, Joel M.

In: Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine, Vol. 21, No. 1, 01.03.2019, p. 63-68.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent β-lactam antibiotic infusion in critically ill patients with sepsis

T2 - BLING III

AU - Lipman, Jeffrey

AU - Brett, Stephen J.

AU - De Waele, Jan J.

AU - Cotta, Menino O.

AU - Davis, Joshua S.

AU - Finfer, Simon

AU - Glass, Parisa

AU - Knowles, Serena

AU - McGuinness, Shay

AU - Myburgh, John

AU - Paterson, David L.

AU - Peake, Sandra

AU - Rajbhandari, Dorrilyn

AU - Rhodes, Andrew

AU - Roberts, Jason A.

AU - Shirwadkar, Charudatt

AU - Starr, Therese

AU - Taylor, Colman

AU - Billot, Laurent

AU - Dulhunty, Joel M.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background and Rationale: β-Lactam antibiotics display a time-dependent mechanism of action, with evidence suggesting improved outcomes when administering these drugs via continuous infusion compared with standard intermittent infusion. However, there is no phase 3 randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis. Design and Setting: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 RCT to compare continuous infusion with standard intermittent infusion of β-lactam antibiotics in critically ill patients with sepsis. The study will be conducted in about 70 intensive care units (ICUs) in Australia, New Zealand, the United Kingdom, Belgium and selected other countries, from 2018 to 2021. Participants and Interventions: BLING III will recruit 7000 critically ill patients with sepsis being treated with one of two β-lactam antibiotics (piperacillin-tazobactam or meropenem) to receive the β-lactam antibiotic by either continuous or intermittent infusion. Main Outcome Measures: The primary outcome is allcause mortality within 90 days after randomisation. Secondary outcomes are clinical cure at Day 14 after randomisation, new acquisition, colonisation or infection with a multiresistant organism or Clostridium difficile diarrhoea up to 14 days after randomisation, all-cause ICU mortality and all-cause hospital mortality. Tertiary outcomes are ICU length of stay, hospital length of stay and duration of mechanical ventilation and duration of renal replacement therapy up to 90 days after randomisation. Results and Conclusions: The BLING III study will compare the effect on 90-day mortality of β-lactam antibiotics administered via continuous versus intermittent infusion in 7000 critically ill patients with sepsis. Trial Registration: ClinicalTrials.gov Registry (NCT03213990).

AB - Background and Rationale: β-Lactam antibiotics display a time-dependent mechanism of action, with evidence suggesting improved outcomes when administering these drugs via continuous infusion compared with standard intermittent infusion. However, there is no phase 3 randomised controlled trial (RCT) evidence to support one method of administration over another in critically ill patients with sepsis. Design and Setting: The β-Lactam Infusion Group (BLING) III study is a prospective, multicentre, open, phase 3 RCT to compare continuous infusion with standard intermittent infusion of β-lactam antibiotics in critically ill patients with sepsis. The study will be conducted in about 70 intensive care units (ICUs) in Australia, New Zealand, the United Kingdom, Belgium and selected other countries, from 2018 to 2021. Participants and Interventions: BLING III will recruit 7000 critically ill patients with sepsis being treated with one of two β-lactam antibiotics (piperacillin-tazobactam or meropenem) to receive the β-lactam antibiotic by either continuous or intermittent infusion. Main Outcome Measures: The primary outcome is allcause mortality within 90 days after randomisation. Secondary outcomes are clinical cure at Day 14 after randomisation, new acquisition, colonisation or infection with a multiresistant organism or Clostridium difficile diarrhoea up to 14 days after randomisation, all-cause ICU mortality and all-cause hospital mortality. Tertiary outcomes are ICU length of stay, hospital length of stay and duration of mechanical ventilation and duration of renal replacement therapy up to 90 days after randomisation. Results and Conclusions: The BLING III study will compare the effect on 90-day mortality of β-lactam antibiotics administered via continuous versus intermittent infusion in 7000 critically ill patients with sepsis. Trial Registration: ClinicalTrials.gov Registry (NCT03213990).

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UR - https://www.ncbi.nlm.nih.gov/pubmed/30857514#

M3 - Article

VL - 21

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JO - Critical Care and Resuscitation

JF - Critical Care and Resuscitation

SN - 1441-2772

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