Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
7203 participants
INTERVENTIONAL
2018-03-26
2023-06-29
Brief Summary
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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.
Detailed Description
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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
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Continuous Infusion
The prescribed Beta-lactam is administered by a continuous infusion.
Continuous infusion
Clinician prescribed beta-lactam antibiotic will be administered via continuous infusion for as long as prescribed whilst in the ICU
Intermittent infusion
the prescribed Beta-lactam is administered by intermittent infusion over 30 minutes
Intermittent infusion
Clinician prescribed beta-lactam antibiotic will be administered via intermittent infusion for as long as prescribed whilst in the ICU
Interventions
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Continuous infusion
Clinician prescribed beta-lactam antibiotic will be administered via continuous infusion for as long as prescribed whilst in the ICU
Intermittent infusion
Clinician prescribed beta-lactam antibiotic will be administered via intermittent infusion for as long as prescribed whilst in the ICU
Eligibility Criteria
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Inclusion Criteria
2. 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
3. The treating physician has chosen piperacillin-tazobactam or meropenem to treat the episode of infection
4. The treating physician is uncertain if administration of the chosen antibiotic by intermittent or continuous infusion is superior
5. 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
Exclusion Criteria
2. Receipt of piperacillin-tazobactam or meropenem for more than 24 hours during current infectious episode
3. Patients who are known or suspected to be pregnant
4. Patient has a known allergy to piperacillin-tazobactam or meropenem or penicillin
5. Receiving renal replacement therapy at the time of assessment for eligibility
6. 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
7. Death is deemed imminent and inevitable
8. The patient has previously been enrolled in BLING III
18 Years
ALL
No
Sponsors
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National Health and Medical Research Council, Australia
OTHER
Australian and New Zealand Intensive Care Society Clinical Trials Group
NETWORK
The George Institute
OTHER
Responsible Party
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Principal Investigators
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Jeffrey Lipman
Role: STUDY_CHAIR
The George Institute
Locations
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Bankstown Hospital
Bankstown, New South Wales, Australia
Blacktown Hospital
Blacktown, New South Wales, Australia
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
St Vincents Hosptial
Darlinghurst, New South Wales, Australia
Gosford Hospital
Gosford, New South Wales, Australia
John Hunter Hospital
New Lambton Heights, New South Wales, Australia
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia
St George Hospital
Sydney, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Royal Darwin Hospital
Casuarina, Northern Territory, Australia
The Wesley Hospital
Auchenflower, Queensland, Australia
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia
Caboolture Hospital
Caboolture, Queensland, Australia
Logan Hospital
Meadowbrook, Queensland, Australia
Redcliffe Hospital
Redcliffe, Queensland, Australia
Gold Coast University Hospital
Southport, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
The Queen Elizabeth Hospital
Adelaide, South Australia, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, Australia
Royal Hobart Hospital
Hobart, Tasmania, Australia
Bendigo Hospital
Bendigo, Victoria, Australia
Box Hill Hospital - Eastern Health
Box Hill, Victoria, Australia
Geelong University Hospital
Geelong, Victoria, Australia
Austin Hospital
Heidelberg, Victoria, Australia
Royal Melbourne Hospital
Melbourne, Victoria, Australia
Hôpital Erasme
Brussels, Anderlecht, Belgium
ZNA Stuivenberg
Antwerp, , Belgium
Universitair ziekenhuis Antwerpen
Antwerp, , Belgium
Universitair ziekenhuis Brussel
Brussels, , Belgium
Civil Hospital Marie Curie
Charleroi, , Belgium
Maria Middelares
Ghent, , Belgium
Universitair ziekenhuis Gent
Ghent, , Belgium
Clinique Saint Pierre
Ottignies, , Belgium
Ch Salon de Provence
Salon-de-Provence, Bouche Du Rhone, France
Nimes University Hospital
Nîmes, Nimes, France
Centre Hospitalier Henri Duffaut
Avignon, Vaucluse, France
Brabois
Nancy, , France
Poitiers University Hospital
Poitiers, , France
Hospital Universiti Sains Malaysia
Kota Bharu, Kelantan, Malaysia
University Malaya Medical Centre
Kuala Lumpur, Selangor, Malaysia
Auckland City Hospital - CVICU
Auckland, , New Zealand
Auckland City Hospital - DCCM
Auckland, , New Zealand
Middlmore Hospital
Auckland, , New Zealand
Christchurch Hospital
Christchurch, , New Zealand
Waikato Hospital
Hamilton, , New Zealand
Wellington Hospital
Wellington, , New Zealand
Helsingborg Hospital
Helsingborg, , Sweden
Skane Lund University Hospital
Lund, , Sweden
Skane University Malmo Hospital
Malmo, , Sweden
Royal Berkshire Hospital
Reading, Berkshire, United Kingdom
Kings College Hospital
London, Brixton, United Kingdom
Princess Royal University Hospital
Orpington, Bromley, United Kingdom
Stoke Mandeville Hospital
Aylesbury, Buckinghamshire, United Kingdom
Milton Keynes University Hospital
Milton Keynes, Buckinghamshire, United Kingdom
Countess of Chester Hospital
Chester, Cheshire, United Kingdom
Dorset County Hospital
Dorchester, Dorset, United Kingdom
Poole Hospital
Poole, Dorset, United Kingdom
University Hospital of North Tees
Stockton-on-Tees, Durham, United Kingdom
Ipswich Hospital
Ipswich, East Suffolk, United Kingdom
Darent Valley Hospital
Dartford, England, United Kingdom
Maidstone Hospital
Maidstone, England, United Kingdom
Derriford Hospital
Plymouth, England, United Kingdom
Broomfield Hospital
Chelmsford, Essex, United Kingdom
Golden Jubilee National Hospital
Clydebank, Glasgow, United Kingdom
Royal Bolton Hospital
Bolton, Greater Manchester, United Kingdom
Charing Cross Hospital
London, Hammersmith, United Kingdom
Basingstoke and North Hampshire Hospital
Basingstoke, Hampshire, United Kingdom
Queen Alexandra Hospital
Portsmouth, Hampshire, United Kingdom
Southampton General Hospital
Southampton, Hampshire, United Kingdom
Royal Hampshire County Hospital
Winchester, Hampshire, United Kingdom
Hereford County Hospital
Hereford, Herefordshire, United Kingdom
Watford General Hospital
Watford, Hertfordshire, United Kingdom
Medway Maritime Hospital
Gillingham, Kent, United Kingdom
Kingston Hospital
Kingston upon Thames, Kent, United Kingdom
Tunbridge Wells Hospital
Royal Tunbridge Wells, Kent, United Kingdom
Blackpool Victoria Hospital
Blackpool, Lancashire, United Kingdom
The Royal Marsden
Chelsea, London, United Kingdom
Guy's & St Thomas' Hospital London
Lambeth, London, United Kingdom
St Georges Hospital
Tooting, London, United Kingdom
The Royal London Hospital
Whitechapel, London, United Kingdom
Royal Victoria Infirmary
Newcastle, Northhumberland, United Kingdom
Newcastle Freeman Hospital
Newcastle, Northumberland, United Kingdom
The Queens Medical Centre
Nottingham, Nottinghamshire, United Kingdom
Kingsmill Hospital
Sutton in Ashfield, Nottinghamshire, United Kingdom
St Marys Hospital
London, Paddington, United Kingdom
Whiston Hospital
Rainhill, Prescot, United Kingdom
Hammersmith Hospital
London, Shepherds Bush, United Kingdom
James Cook University Hospital South Tees
Middlesbrough, South Tees, United Kingdom
Frimley Park Hospital
Frimley, Surrey, United Kingdom
Royal Surrey County Hospital
Guildford, Surrey, United Kingdom
Sunderland Royal Hospital
Sunderland, Tyne and Wear, United Kingdom
University Hospital of Wales
Cardiff, Wales, United Kingdom
University Hospital Coventry & Warwickshire
Coventry, Warwickshire, United Kingdom
Queen Elizabeth Medical Centre
Birmingham, West Midlands, United Kingdom
Pinderfields General Hospital
Wakefield, West Yorkshire, United Kingdom
Bristol Royal Infirmary
Bristol, , United Kingdom
Northumbria Specialist Emergency Hospital
Cramlington, , United Kingdom
Ninewells Hospital
Dundee, , United Kingdom
Glasgow Royal Infirmary
Glasgow, , United Kingdom
Hull Royal Infirmary
Hull, , United Kingdom
Whittington Health
London, , United Kingdom
Queen's Hospital
Romford, , United Kingdom
Salford Royal Hospital
Salford, , United Kingdom
Countries
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References
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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.
Provided Documents
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Document Type: Study Protocol: PKPD Substudy
Document Type: Study Protocol: BLING III PKPD substudy protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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TGI-CCT254643
Identifier Type: -
Identifier Source: org_study_id