NCT03213990

Brief Summary

The purpose of this study is to find out whether continuous infusion of beta-lactam antibiotics or intermittent infusion or beta-lactam antibiotics, offers more health advantages to patients or if there is no difference. The investigators will be looking to see whether patients receiving beta-lactams via one administration method or the other have a better chance of recovering from their illness. They will also be looking at long term outcomes such as quality-of-life and healthcare resource use. Sepsis is caused by toxic substances (toxins) from bacteria and other organism entering the bloodstream from a site of infection. In some people, the infection can progress to sepsis and septic shock where the functions of organs in the body are affected. Patients suffering from sepsis and septic shock are commonly managed in the intensive care unit (ICU) where they are prescribed antibiotics as standard therapy, as well as other therapies to support the functions of the body. Beta-lactam antibiotics are a group of antibiotics commonly used to treat infection in patients with sepsis and septic shock. Currently, beta-lactam antibiotics are most commonly given to patients be intermittent infusions, that is, given at regular intervals throughout 24 hours. New research suggests that giving beta-lactam antibiotics as a continuous infusion may mean that antibiotic concentrations in the blood remain more consistent and may be more effective at killing bacteria. However, the benefit to the patient by giving beta-lactams via continuous infusion has not been tested in a high-quality, large clinical trial.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
7,203

participants targeted

Target at P75+ for not_applicable sepsis

Timeline
Completed

Started Mar 2018

Longer than P75 for not_applicable sepsis

Geographic Reach
7 countries

103 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 5, 2017

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 11, 2017

Completed
9 months until next milestone

Study Start

First participant enrolled

March 26, 2018

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 12, 2023

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 29, 2023

Completed
Last Updated

December 12, 2023

Status Verified

December 1, 2023

Enrollment Period

5 years

First QC Date

June 5, 2017

Last Update Submit

December 10, 2023

Conditions

Keywords

SepsisBeta-lactam antibiotics

Outcome Measures

Primary Outcomes (1)

  • All-cause mortality

    Patient mortality status assessed at 90 days after randomisation

    90 Days after randomisation

Secondary Outcomes (4)

  • Clinical Cure

    Day 14 post randomisation

  • New acquisition, colonisation or infection

    up to 14 days post randomisation or hospital discharge, whichever is sooner

  • All cause ICU mortality

    up to 90 days

  • All cause hospital mortality

    up to 90 days

Other Outcomes (5)

  • ICU length of stay

    up to 90 days

  • Hospital length of stay

    up to 90 days

  • Quality of life

    90 days after randomisation

  • +2 more other outcomes

Study Arms (2)

Continuous Infusion

OTHER

The prescribed Beta-lactam is administered by a continuous infusion.

Other: Continuous infusion

Intermittent infusion

OTHER

the prescribed Beta-lactam is administered by intermittent infusion over 30 minutes

Other: Intermittent infusion

Interventions

Clinician prescribed beta-lactam antibiotic will be administered via continuous infusion for as long as prescribed whilst in the ICU

Continuous Infusion

Clinician prescribed beta-lactam antibiotic will be administered via intermittent infusion for as long as prescribed whilst in the ICU

Intermittent infusion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Documented site of infection or strong suspicion of infection
  • At the time of the assessment of suitability for the study, the treating physician expects the patient will require treatment in the ICU that extends beyond the next calendar day
  • The treating physician has chosen piperacillin-tazobactam or meropenem to treat the episode of infection
  • The treating physician is uncertain if administration of the chosen antibiotic by intermittent or continuous infusion is superior
  • One or more organ dysfunction entry criteria in the previous 24 hours
  • i. Mean arterial pressure \< 60 mmHg for at least 1 hour
  • ii. Vasopressors required for \> 4 hours
  • iii. Respiratory support using supplemental high flow nasal prongs, continuous positive airway pressure, bilevel positive airway pressure or invasive mechanical ventilation for at least 1 hour
  • iv. Serum creatinine concentration \> 220 µmol/L

You may not qualify if:

  • Age less than 18 years
  • Receipt of piperacillin-tazobactam or meropenem for more than 24 hours during current infectious episode
  • Patients who are known or suspected to be pregnant
  • Patient has a known allergy to piperacillin-tazobactam or meropenem or penicillin
  • Receiving renal replacement therapy at the time of assessment for eligibility
  • The treating physician is not committed to provision of advanced life-support, including mechanical ventilation, dialysis and vasopressor administration, for at least the next 48 hours
  • Death is deemed imminent and inevitable
  • The patient has previously been enrolled in BLING III

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (103)

Bankstown Hospital

Bankstown, New South Wales, 2200, Australia

Location

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

St Vincents Hosptial

Darlinghurst, New South Wales, 2010, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

St George Hospital

Sydney, New South Wales, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Darwin Hospital

Casuarina, Northern Territory, 0811, Australia

Location

The Wesley Hospital

Auchenflower, Queensland, 4066, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Location

Caboolture Hospital

Caboolture, Queensland, 4510, Australia

Location

Logan Hospital

Meadowbrook, Queensland, 4131, Australia

Location

Redcliffe Hospital

Redcliffe, Queensland, 4020, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

The Queen Elizabeth Hospital

Adelaide, South Australia, Australia

Location

Lyell McEwin Hospital

Elizabeth Vale, South Australia, 5112, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7001, Australia

Location

Bendigo Hospital

Bendigo, Victoria, 3550, Australia

Location

Box Hill Hospital - Eastern Health

Box Hill, Victoria, 3128, Australia

Location

Geelong University Hospital

Geelong, Victoria, 3220, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

HĂ´pital Erasme

Brussels, Anderlecht, , 1070, Belgium

Location

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

Universitair ziekenhuis Antwerpen

Antwerp, 2610, Belgium

Location

Universitair ziekenhuis Brussel

Brussels, 1090, Belgium

Location

Civil Hospital Marie Curie

Charleroi, Belgium

Location

Maria Middelares

Ghent, 9000, Belgium

Location

Universitair ziekenhuis Gent

Ghent, 9000, Belgium

Location

Clinique Saint Pierre

Ottignies, 1340, Belgium

Location

Ch Salon de Provence

Salon-de-Provence, Bouche Du Rhone, 13300, France

Location

Nimes University Hospital

Nîmes, Nimes, 30900, France

Location

Centre Hospitalier Henri Duffaut

Avignon, Vaucluse, 84902, France

Location

Brabois

Nancy, France

Location

Poitiers University Hospital

Poitiers, France

Location

Hospital Universiti Sains Malaysia

Kota Bharu, Kelantan, 16150, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, Selangor, 59100, Malaysia

Location

Auckland City Hospital - CVICU

Auckland, 1142, New Zealand

Location

Auckland City Hospital - DCCM

Auckland, 1142, New Zealand

Location

Middlmore Hospital

Auckland, New Zealand

Location

Christchurch Hospital

Christchurch, 8011, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Wellington Hospital

Wellington, 6021, New Zealand

Location

Helsingborg Hospital

Helsingborg, 25223, Sweden

Location

Skane Lund University Hospital

Lund, 22242, Sweden

Location

Skane University Malmo Hospital

Malmo, 21421, Sweden

Location

Royal Berkshire Hospital

Reading, Berkshire, RG1 5AN, United Kingdom

Location

Kings College Hospital

London, Brixton, SE5 9RS, United Kingdom

Location

Princess Royal University Hospital

Orpington, Bromley, BR6 8ND, United Kingdom

Location

Stoke Mandeville Hospital

Aylesbury, Buckinghamshire, HP21 8AL, United Kingdom

Location

Milton Keynes University Hospital

Milton Keynes, Buckinghamshire, MK6 5LD, United Kingdom

Location

Countess of Chester Hospital

Chester, Cheshire, CH21UL, United Kingdom

Location

Dorset County Hospital

Dorchester, Dorset, DT1 2JY, United Kingdom

Location

Poole Hospital

Poole, Dorset, BH15 2JB, United Kingdom

Location

University Hospital of North Tees

Stockton-on-Tees, Durham, TS19 8PE, United Kingdom

Location

Ipswich Hospital

Ipswich, East Suffolk, IP4 5PD, United Kingdom

Location

Darent Valley Hospital

Dartford, England, DA28DA, United Kingdom

Location

Maidstone Hospital

Maidstone, England, ME169QQ, United Kingdom

Location

Derriford Hospital

Plymouth, England, PL68DH, United Kingdom

Location

Broomfield Hospital

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

Golden Jubilee National Hospital

Clydebank, Glasgow, G81 4HX, United Kingdom

Location

Royal Bolton Hospital

Bolton, Greater Manchester, BL4 0JR, United Kingdom

Location

Charing Cross Hospital

London, Hammersmith, SW6 8RF, United Kingdom

Location

Basingstoke and North Hampshire Hospital

Basingstoke, Hampshire, RG24 9NA, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, Hampshire, PO6 3LY, United Kingdom

Location

Southampton General Hospital

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Royal Hampshire County Hospital

Winchester, Hampshire, SO22 5DG, United Kingdom

Location

Hereford County Hospital

Hereford, Herefordshire, HR1 2ER, United Kingdom

Location

Watford General Hospital

Watford, Hertfordshire, WD18 0HB, United Kingdom

Location

Medway Maritime Hospital

Gillingham, Kent, ME7 5NY, United Kingdom

Location

Kingston Hospital

Kingston upon Thames, Kent, KT2 7QB, United Kingdom

Location

Tunbridge Wells Hospital

Royal Tunbridge Wells, Kent, TN2 4QJ, United Kingdom

Location

Blackpool Victoria Hospital

Blackpool, Lancashire, FY3 8NR, United Kingdom

Location

The Royal Marsden

Chelsea, London, SW3 6JJ, United Kingdom

Location

Guy's & St Thomas' Hospital London

Lambeth, London, SE1 7EH, United Kingdom

Location

St Georges Hospital

Tooting, London, SW17 0QT, United Kingdom

Location

The Royal London Hospital

Whitechapel, London, E1 1BB, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, Northhumberland, NE1 4LP, United Kingdom

Location

Newcastle Freeman Hospital

Newcastle, Northumberland, NE7 7DN, United Kingdom

Location

The Queens Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

Kingsmill Hospital

Sutton in Ashfield, Nottinghamshire, NG17 4JL, United Kingdom

Location

St Marys Hospital

London, Paddington, W2 1NY, United Kingdom

Location

Whiston Hospital

Rainhill, Prescot, L35 5DR, United Kingdom

Location

Hammersmith Hospital

London, Shepherds Bush, W12 0HS,, United Kingdom

Location

James Cook University Hospital South Tees

Middlesbrough, South Tees, TS4 3BW, United Kingdom

Location

Frimley Park Hospital

Frimley, Surrey, GU16 7UJ, United Kingdom

Location

Royal Surrey County Hospital

Guildford, Surrey, GU2 7XX, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, Tyne and Wear, SR4 7TP, United Kingdom

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

University Hospital Coventry & Warwickshire

Coventry, Warwickshire, CV2 2DX, United Kingdom

Location

Queen Elizabeth Medical Centre

Birmingham, West Midlands, B12 2TH, United Kingdom

Location

Pinderfields General Hospital

Wakefield, West Yorkshire, WF1 4DG, United Kingdom

Location

Bristol Royal Infirmary

Bristol, BS1 3NU, United Kingdom

Location

Northumbria Specialist Emergency Hospital

Cramlington, United Kingdom

Location

Ninewells Hospital

Dundee, United Kingdom

Location

Glasgow Royal Infirmary

Glasgow, United Kingdom

Location

Hull Royal Infirmary

Hull, HU3 2JZ, United Kingdom

Location

Whittington Health

London, N19 5NF, United Kingdom

Location

Queen's Hospital

Romford, United Kingdom

Location

Salford Royal Hospital

Salford, M6 8HD, United Kingdom

Location

Related Publications (2)

  • Dulhunty JM, Brett SJ, De Waele JJ, Rajbhandari D, Billot L, Cotta MO, Davis JS, Finfer S, Hammond NE, Knowles S, Liu X, McGuinness S, Mysore J, Paterson DL, Peake S, Rhodes A, Roberts JA, Roger C, Shirwadkar C, Starr T, Taylor C, Myburgh JA, Lipman J; BLING III Study Investigators. Continuous vs Intermittent beta-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial. JAMA. 2024 Aug 27;332(8):629-637. doi: 10.1001/jama.2024.9779.

  • 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. A protocol for a phase 3 multicentre randomised controlled trial of continuous versus intermittent beta-lactam antibiotic infusion in critically ill patients with sepsis: BLING III. Crit Care Resusc. 2019 Mar;21(1):63-68.

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

InfectionsSystemic Inflammatory Response SyndromeInflammationPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Jeffrey Lipman

    The George Institute

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 5, 2017

First Posted

July 11, 2017

Study Start

March 26, 2018

Primary Completion

April 12, 2023

Study Completion

June 29, 2023

Last Updated

December 12, 2023

Record last verified: 2023-12

Locations