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SepsisBLING IIINCT03213990

Beta-Lactam InfusioN Group Study

A study testing Continuous infusion and Intermittent infusion in people with Sepsis, run by The George Institute at 103 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sepsis
What is being tested?
Continuous infusion and Intermittent infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7,203 participants
Where
103 sitesin 7 countries
Study dates
26 Mar 2018to 29 Jun 2023
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

103 sites in 7 countries.

103 sites in 7 countries

United Kingdom54 sites

  • Stoke Mandeville Hospital

    Aylesbury, Buckinghamshire, HP21 8AL

  • Basingstoke and North Hampshire Hospital

    Basingstoke, Hampshire, RG24 9NA

  • Queen Elizabeth Medical Centre

    Birmingham, West Midlands, B12 2TH

  • Blackpool Victoria Hospital

    Blackpool, Lancashire, FY3 8NR

  • Royal Bolton Hospital

    Bolton, Greater Manchester, BL4 0JR

  • Bristol Royal Infirmary

    Bristol, BS1 3NU

  • University Hospital of Wales

    Cardiff, Wales, CF14 4XW

  • Broomfield Hospital

    Chelmsford, Essex, CM1 7ET

  • The Royal Marsden

    Chelsea, London, SW3 6JJ

  • Countess of Chester Hospital

    Chester, Cheshire, CH21UL

  • Golden Jubilee National Hospital

    Clydebank, Glasgow, G81 4HX

  • University Hospital Coventry & Warwickshire

    Coventry, Warwickshire, CV2 2DX

  • Northumbria Specialist Emergency Hospital

    Cramlington

  • Darent Valley Hospital

    Dartford, England, DA28DA

  • Dorset County Hospital

    Dorchester, Dorset, DT1 2JY

  • Ninewells Hospital

    Dundee

  • Frimley Park Hospital

    Frimley, Surrey, GU16 7UJ

  • Medway Maritime Hospital

    Gillingham, Kent, ME7 5NY

  • Glasgow Royal Infirmary

    Glasgow

  • Royal Surrey County Hospital

    Guildford, Surrey, GU2 7XX

  • Hereford County Hospital

    Hereford, Herefordshire, HR1 2ER

  • Hull Royal Infirmary

    Hull, HU3 2JZ

  • Ipswich Hospital

    Ipswich, East Suffolk, IP4 5PD

  • Kingston Hospital

    Kingston upon Thames, Kent, KT2 7QB

  • Guy's & St Thomas' Hospital London

    Lambeth, London, SE1 7EH

  • Kings College Hospital

    London, Brixton, SE5 9RS

  • Charing Cross Hospital

    London, Hammersmith, SW6 8RF

  • St Marys Hospital

    London, Paddington, W2 1NY

  • Hammersmith Hospital

    London, Shepherds Bush, W12 0HS,

  • Whittington Health

    London, N19 5NF

  • Maidstone Hospital

    Maidstone, England, ME169QQ

  • James Cook University Hospital South Tees

    Middlesbrough, South Tees, TS4 3BW

  • Milton Keynes University Hospital

    Milton Keynes, Buckinghamshire, MK6 5LD

  • Royal Victoria Infirmary

    Newcastle, Northhumberland, NE1 4LP

  • Newcastle Freeman Hospital

    Newcastle, Northumberland, NE7 7DN

  • The Queens Medical Centre

    Nottingham, Nottinghamshire, NG7 2UH

  • Princess Royal University Hospital

    Orpington, Bromley, BR6 8ND

  • Derriford Hospital

    Plymouth, England, PL68DH

  • Poole Hospital

    Poole, Dorset, BH15 2JB

  • Queen Alexandra Hospital

    Portsmouth, Hampshire, PO6 3LY

  • Whiston Hospital

    Rainhill, Prescot, L35 5DR

  • Royal Berkshire Hospital

    Reading, Berkshire, RG1 5AN

  • Queen's Hospital

    Romford

  • Tunbridge Wells Hospital

    Royal Tunbridge Wells, Kent, TN2 4QJ

  • Salford Royal Hospital

    Salford, M6 8HD

  • Southampton General Hospital

    Southampton, Hampshire, SO16 6YD

  • University Hospital of North Tees

    Stockton-on-Tees, Durham, TS19 8PE

  • Sunderland Royal Hospital

    Sunderland, Tyne and Wear, SR4 7TP

  • Kingsmill Hospital

    Sutton in Ashfield, Nottinghamshire, NG17 4JL

  • St Georges Hospital

    Tooting, London, SW17 0QT

  • Pinderfields General Hospital

    Wakefield, West Yorkshire, WF1 4DG

  • Watford General Hospital

    Watford, Hertfordshire, WD18 0HB

  • The Royal London Hospital

    Whitechapel, London, E1 1BB

  • Royal Hampshire County Hospital

    Winchester, Hampshire, SO22 5DG

Other trials in United Kingdom

Australia25 sites

  • The Queen Elizabeth Hospital

    Adelaide, South Australia

  • The Wesley Hospital

    Auchenflower, Queensland, 4066

  • Bankstown Hospital

    Bankstown, New South Wales, 2200

  • Bendigo Hospital

    Bendigo, Victoria, 3550

  • Blacktown Hospital

    Blacktown, New South Wales, 2148

  • Box Hill Hospital - Eastern Health

    Box Hill, Victoria, 3128

  • Royal Brisbane and Women's Hospital

    Brisbane, Queensland

  • Caboolture Hospital

    Caboolture, Queensland, 4510

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • Royal Darwin Hospital

    Casuarina, Northern Territory, 0811

  • St Vincents Hosptial

    Darlinghurst, New South Wales, 2010

  • Lyell McEwin Hospital

    Elizabeth Vale, South Australia, 5112

  • Geelong University Hospital

    Geelong, Victoria, 3220

  • Gosford Hospital

    Gosford, New South Wales, 2250

  • Austin Hospital

    Heidelberg, Victoria, 3084

  • Royal Hobart Hospital

    Hobart, Tasmania, 7001

  • Logan Hospital

    Meadowbrook, Queensland, 4131

  • Royal Melbourne Hospital

    Melbourne, Victoria, 3050

  • John Hunter Hospital

    New Lambton Heights, New South Wales, 2305

  • Redcliffe Hospital

    Redcliffe, Queensland, 4020

  • Royal North Shore Hospital

    Saint Leonards, New South Wales, 2065

  • Gold Coast University Hospital

    Southport, Queensland, 4215

  • St George Hospital

    Sydney, New South Wales

  • Westmead Hospital

    Westmead, New South Wales, 2145

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Belgium8 sites

  • ZNA Stuivenberg

    Antwerp, 2060

  • Universitair ziekenhuis Antwerpen

    Antwerp, 2610

  • Hôpital Erasme

    Brussels, Anderlecht, , 1070

  • Universitair ziekenhuis Brussel

    Brussels, 1090

  • Civil Hospital Marie Curie

    Charleroi

  • Maria Middelares

    Ghent, 9000

  • Universitair ziekenhuis Gent

    Ghent, 9000

  • Clinique Saint Pierre

    Ottignies, 1340

Other trials in Belgium

New Zealand6 sites

  • Auckland City Hospital - CVICU

    Auckland, 1142

  • Auckland City Hospital - DCCM

    Auckland, 1142

  • Middlmore Hospital

    Auckland

  • Christchurch Hospital

    Christchurch, 8011

  • Waikato Hospital

    Hamilton, 3240

  • Wellington Hospital

    Wellington, 6021

Other trials in New Zealand

France5 sites

  • Centre Hospitalier Henri Duffaut

    Avignon, Vaucluse, 84902

  • Brabois

    Nancy

  • Nimes University Hospital

    Nîmes, Nimes, 30900

  • Poitiers University Hospital

    Poitiers

  • Ch Salon de Provence

    Salon-de-Provence, Bouche Du Rhone, 13300

Other trials in France

Sweden3 sites

  • Helsingborg Hospital

    Helsingborg, 25223

  • Skane Lund University Hospital

    Lund, 22242

  • Skane University Malmo Hospital

    Malmö, 21421

Other trials in Sweden

Malaysia2 sites

  • Hospital Universiti Sains Malaysia

    Kota Bharu, Kelantan, 16150

  • University Malaya Medical Centre

    Kuala Lumpur, Selangor, 59100

Other trials in Malaysia

About this study

Official title: A Phase III Randomised Controlled Trial of Continuous Beta-lactam Infusion Compared With Intermittent Beta-lactam Dosing in Critically Ill Patients

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.

Read more

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.

Read the detailed description

Aim To conduct a multicentre randomised, controlled trial (RCT) to determine whether continuous infusion of a beta-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all cause Day 90 mortality compared with intermittent beta-lactam antibiotic infusion in critically ill patients with sepsis.

Hypothesis The BLING III Study will test the hypothesis that patients managed in the ICU with sepsis, the administration of beta-lactam antibiotics via continuous infusion decreases Day 90 mortality compared with intermittent infusion Design This BLING III study is a prospective, multicentre, open, phase III, RCT. Participants commenced on one of two beta-lactam antibiotics (piperacillin-tazobactam or meropenem) will be randomised to receive the beta-lactam antibiotic via either continuous infusion or intermittent infusion over 30 minutes for the treatment course while in the ICU for up to 90 days after randomisation. For participants where the beta-lactam antibiotic is subsequently changed from piperacillin-tazobactam to meropenem or vice versa for ongoing treatment of the infectious episode, the new prescription will continue to be administered in the allocated method (continuous infusion or intermittent infusion over 30 minutes).

Permuted block randomisation with variable block sizes and stratified by site will be conducted via a password-protected, secure web-based interface.

The primary endpoint for this trial will be death from all causes at 90 days.

7,000 patients will be enrolled into this study from approximately 70 ICUs worldwide, with approximately 35 ICUs in Australian and New Zealand hospitals.

For eligible patients, the administration method of beta-lactam antibiotic, either piperacillin-tazobactam or meropenem, will be randomised to either continuous infusion or intermittent infusion over 30 minutes. The choice of beta-lactam antibiotic and the dose and dosing interval (i.e. the dose the patient will receive in 24 hours) will be determined by the treating physician prior to randomisation.

For all patients, data will be collected at baseline and daily whilst in the ICU. Patients will be followed up to day 14, regardless of location in the hospital, to determine test of cure and to identify new acquisition, colonisation or infection with an multi-resistant organism. Additional follow up will occur at 90 days post randomisation.

Conditions
Sepsis
Being tested
Continuous infusion, Intermittent infusion
Keywords
Sepsis, Beta-lactam antibiotics
Medical subject headings
Sepsis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Continuous infusionOther

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

  • Intermittent infusionOther

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

Study groups in NCT03213990
Study groupRoleWhat they receive
Continuous InfusionOtherThe prescribed Beta-lactam is administered by a continuous infusion.
Receives: Other: Continuous infusion
Intermittent infusionOtherthe prescribed Beta-lactam is administered by intermittent infusion over 30 minutes
Receives: Other: Intermittent infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. All-cause mortality

    Patient mortality status assessed at 90 days after randomisation

    Measured: 90 Days after randomisation

Secondary outcomes (4)

  1. Clinical Cure

    Clinical cure will be defined as the completion of the beta-lactam antibiotic treatment course (on or prior to Day 14) without recommencement of antibiotic therapy within 48 hours of cessation.

    Participants discharged from hospital within 14 days following randomisation will be considered to meet the definition of clinical cure. Participants who decease while receiving the antibiotic treatment course or where antibiotic therapy is ceased in the setting of death being deemed imminent and inevitable, will be assessed as not meeting the criteria for clinical cure.

    Measured: Day 14 post randomisation

  2. New acquisition, colonisation or infection

    New acquisition, colonisation or infection with an Multi-resistant organism (MRO) or Clostridium difficile diarrhoea

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

  3. All cause ICU mortality

    Patient mortality status assessed at ICU discharge

    Measured: up to 90 days

  4. All cause hospital mortality

    Patient mortality status assessed at hospital discharge

    Measured: up to 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jul 2017
  2. Study start26 Mar 2018
  3. Primary completion12 Apr 2023
  4. Study completion29 Jun 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
7,203 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03213990
Sponsor's protocol ID
TGI-CCT254643
Acronym
BLING III
Status last verified
Dec 2023
First submitted
5 Jun 2017
Last updated
12 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Yet to be decided

Publications

  • 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.

    PubMed 38864155

  • 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.

    PubMed 30857514

Questions about this trial

What is this clinical trial studying?

A study testing Continuous infusion and Intermittent infusion in people with Sepsis, run by The George Institute at 103 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 103 sites in United Kingdom, Australia, Belgium, New Zealand, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

All-cause mortality (time frame: 90 Days after randomisation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03213990, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.

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