Beta-Lactam InfusioN Group Study
- Conditions
- Sepsis
- Interventions
- Other: Intermittent infusionOther: Continuous infusion
- Registration Number
- NCT03213990
- Lead Sponsor
- The George Institute
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7203
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intermittent infusion Intermittent infusion the prescribed Beta-lactam is administered by intermittent infusion over 30 minutes Continuous Infusion Continuous infusion The prescribed Beta-lactam is administered by a continuous infusion.
- Primary Outcome Measures
Name Time Method All-cause mortality 90 Days after randomisation Patient mortality status assessed at 90 days after randomisation
- Secondary Outcome Measures
Name Time Method Clinical Cure Day 14 post randomisation 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.New acquisition, colonisation or infection up to 14 days post randomisation or hospital discharge, whichever is sooner New acquisition, colonisation or infection with an Multi-resistant organism (MRO) or Clostridium difficile diarrhoea
All cause ICU mortality up to 90 days Patient mortality status assessed at ICU discharge
All cause hospital mortality up to 90 days Patient mortality status assessed at hospital discharge
Trial Locations
- Locations (103)
Blacktown Hospital
🇦🇺Blacktown, New South Wales, Australia
Skane Lund University Hospital
🇸🇪Lund, Sweden
The Wesley Hospital
🇦🇺Auchenflower, Queensland, Australia
Auckland City Hospital - CVICU
🇳🇿Auckland, New Zealand
Waikato Hospital
🇳🇿Hamilton, New Zealand
Helsingborg Hospital
🇸🇪Helsingborg, Sweden
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Lyell McEwin Hospital
🇦🇺Elizabeth Vale, South Australia, Australia
Princess Royal University Hospital
🇬🇧Orpington, Bromley, United Kingdom
Ch Salon de Provence
🇫🇷Salon-de-Provence, Bouche Du Rhone, France
Brabois
🇫🇷Nancy, France
Logan Hospital
🇦🇺Meadowbrook, Queensland, Australia
Middlmore Hospital
🇳🇿Auckland, New Zealand
Queen's Hospital
🇬🇧Romford, United Kingdom
Auckland City Hospital - DCCM
🇳🇿Auckland, New Zealand
Royal Victoria Infirmary
🇬🇧Newcastle, Northhumberland, United Kingdom
Skane University Malmo Hospital
🇸🇪Malmo, Sweden
Nimes University Hospital
🇫🇷Nîmes, Nimes, France
Queen Elizabeth Medical Centre
🇬🇧Birmingham, West Midlands, United Kingdom
Poitiers University Hospital
🇫🇷Poitiers, France
St Marys Hospital
🇬🇧London, Paddington, United Kingdom
Wellington Hospital
🇳🇿Wellington, New Zealand
Blackpool Victoria Hospital
🇬🇧Blackpool, Lancashire, United Kingdom
University Hospital of North Tees
🇬🇧Stockton-on-Tees, Durham, United Kingdom
Kings College Hospital
🇬🇧London, Brixton, United Kingdom
Glasgow Royal Infirmary
🇬🇧Glasgow, United Kingdom
Hull Royal Infirmary
🇬🇧Hull, United Kingdom
Derriford Hospital
🇬🇧Plymouth, England, United Kingdom
Queen Alexandra Hospital
🇬🇧Portsmouth, Hampshire, United Kingdom
The Royal London Hospital
🇬🇧Whitechapel, London, United Kingdom
Whiston Hospital
🇬🇧Rainhill, Prescot, United Kingdom
Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom
James Cook University Hospital South Tees
🇬🇧Middlesbrough, South Tees, United Kingdom
Pinderfields General Hospital
🇬🇧Wakefield, West Yorkshire, United Kingdom
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Bankstown Hospital
🇦🇺Bankstown, New South Wales, Australia
John Hunter Hospital
🇦🇺New Lambton Heights, New South Wales, Australia
St Vincents Hosptial
🇦🇺Darlinghurst, New South Wales, Australia
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Caboolture Hospital
🇦🇺Caboolture, Queensland, Australia
Redcliffe Hospital
🇦🇺Redcliffe, Queensland, Australia
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Christchurch Hospital
🇳🇿Christchurch, New Zealand
Royal Berkshire Hospital
🇬🇧Reading, Berkshire, United Kingdom
Countess of Chester Hospital
🇬🇧Chester, Cheshire, United Kingdom
Darent Valley Hospital
🇬🇧Dartford, England, United Kingdom
Maidstone Hospital
🇬🇧Maidstone, England, United Kingdom
Royal Bolton Hospital
🇬🇧Bolton, Greater Manchester, United Kingdom
Watford General Hospital
🇬🇧Watford, Hertfordshire, United Kingdom
Kingston Hospital
🇬🇧Kingston Upon Thames, Kent, United Kingdom
The Royal Marsden
🇬🇧Chelsea, London, United Kingdom
The Queens Medical Centre
🇬🇧Nottingham, Nottinghamshire, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, Tyne And Wear, United Kingdom
Northumbria Specialist Emergency Hospital
🇬🇧Cramlington, United Kingdom
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
St George Hospital
🇦🇺Sydney, New South Wales, Australia
The Queen Elizabeth Hospital
🇦🇺Adelaide, South Australia, Australia
Broomfield Hospital
🇬🇧Chelmsford, Essex, United Kingdom
Stoke Mandeville Hospital
🇬🇧Aylesbury, Buckinghamshire, United Kingdom
Medway Maritime Hospital
🇬🇧Gillingham, Kent, United Kingdom
Tunbridge Wells Hospital
🇬🇧Tunbridge Wells, Kent, United Kingdom
Milton Keynes University Hospital
🇬🇧Milton Keynes, Buckinghamshire, United Kingdom
Clinique Saint Pierre
🇧🇪Ottignies, Belgium
Universitair ziekenhuis Antwerpen
🇧🇪Antwerp, Belgium
Universitair ziekenhuis Brussel
🇧🇪Brussels, Belgium
Civil Hospital Marie Curie
🇧🇪Charleroi, Belgium
Golden Jubilee National Hospital
🇬🇧Clydebank, Glasgow, United Kingdom
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
Frimley Park Hospital
🇬🇧Frimley, Surrey, United Kingdom
Centre Hospitalier Henri Duffaut
🇫🇷Avignon, Vaucluse, France
Hospital Universiti Sains Malaysia
🇲🇾Kota Bharu, Kelantan, Malaysia
Dorset County Hospital
🇬🇧Dorchester, Dorset, United Kingdom
Poole Hospital
🇬🇧Poole, Dorset, United Kingdom
Royal Hampshire County Hospital
🇬🇧Winchester, Hampshire, United Kingdom
Newcastle Freeman Hospital
🇬🇧Newcastle, Northumberland, United Kingdom
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Selangor, Malaysia
Hereford County Hospital
🇬🇧Hereford, Herefordshire, United Kingdom
Royal Surrey County Hospital
🇬🇧Guildford, Surrey, United Kingdom
ZNA Stuivenberg
🇧🇪Antwerpen, Belgium
Basingstoke and North Hampshire Hospital
🇬🇧Basingstoke, Hampshire, United Kingdom
Kingsmill Hospital
🇬🇧Sutton In Ashfield, Nottinghamshire, United Kingdom
Box Hill Hospital - Eastern Health
🇦🇺Box Hill, Victoria, Australia
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Hôpital Erasme
🇧🇪Brussels, Anderlecht, Belgium
Maria Middelares
🇧🇪Gent, Belgium
Universitair ziekenhuis Gent
🇧🇪Gent, Belgium
Bendigo Hospital
🇦🇺Bendigo, Victoria, Australia
University Hospital Coventry & Warwickshire
🇬🇧Coventry, Warwickshire, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, Wales, United Kingdom
Ipswich Hospital
🇬🇧Ipswich, East Suffolk, United Kingdom
Guy's & St Thomas' Hospital London
🇬🇧Lambeth, London, United Kingdom
St Georges Hospital
🇬🇧Tooting, London, United Kingdom
Hammersmith Hospital
🇬🇧London, Shepherds Bush, United Kingdom
Whittington Health
🇬🇧London, United Kingdom
Salford Royal Hospital
🇬🇧Salford, United Kingdom
Royal North Shore Hospital
🇦🇺Saint Leonards, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Queensland, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Geelong University Hospital
🇦🇺Geelong, Victoria, Australia
Royal Darwin Hospital
🇦🇺Casuarina, Northern Territory, Australia
Charing Cross Hospital
🇬🇧London, Hammersmith, United Kingdom