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.


Journal

Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine
ISSN: 1441-2772
Titre abrégé: Crit Care Resusc
Pays: Netherlands
ID NLM: 100888170

Informations de publication

Date de publication:
Mar 2019
Historique:
entrez: 13 3 2019
pubmed: 13 3 2019
medline: 29 5 2019
Statut: ppublish

Résumé

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. 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. 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. 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. 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. ClinicalTrials.gov Registry (NCT03213990).

Sections du résumé

BACKGROUND AND RATIONALE OBJECTIVE
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 METHODS
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 METHODS
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 METHODS
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 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 BACKGROUND
ClinicalTrials.gov Registry (NCT03213990).

Identifiants

pubmed: 30857514

Substances chimiques

Anti-Bacterial Agents 0
beta-Lactams 0
Piperacillin, Tazobactam Drug Combination 157044-21-8
Meropenem FV9J3JU8B1

Banques de données

ClinicalTrials.gov
['NCT03213990']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

63-68

Auteurs

Jeffrey Lipman (J)

Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Joel.Dulhunty@health.qld.gov.au.

Stephen J Brett (SJ)

Imperial College Healthcare NHS Trust, London, United Kingdom.

Jan J De Waele (JJ)

Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium.

Menino O Cotta (MO)

Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Joshua S Davis (JS)

Global and Tropical Health Division, Menzies School of Health Research, Darwin, NT, Australia.

Simon Finfer (S)

Royal North Shore Hospital, Sydney, NSW, Australia.

Parisa Glass (P)

The George Institute for Global Health, Sydney, NSW, Australia.

Serena Knowles (S)

The George Institute for Global Health, Sydney, NSW, Australia.

Shay McGuinness (S)

Auckland City Hospital, Auckland, New Zealand.

John Myburgh (J)

The George Institute for Global Health, Sydney, NSW, Australia.

David L Paterson (DL)

Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Sandra Peake (S)

The Queen Elizabeth Hospital, Adelaide, SA, Australia.

Dorrilyn Rajbhandari (D)

The George Institute for Global Health, Sydney, NSW, Australia.

Andrew Rhodes (A)

St George's University Hospitals NHS Foundation Trust, London, United Kingdom.

Jason A Roberts (JA)

Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Charudatt Shirwadkar (C)

Blacktown Hospital, Sydney, NSW, Australia.

Therese Starr (T)

Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Colman Taylor (C)

The George Institute for Global Health, Sydney, NSW, Australia.

Laurent Billot (L)

The George Institute for Global Health, Sydney, NSW, Australia.

Joel M Dulhunty (JM)

Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

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Classifications MeSH