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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03213990




Registration number
NCT03213990
Ethics application status
Date submitted
5/06/2017
Date registered
11/07/2017
Date last updated
22/02/2019

Titles & IDs
Public title
Beta-Lactam InfusioN Group Study
Scientific title
A Phase III Randomised Controlled Trial of Continuous Beta-lactam Infusion Compared With Intermittent Beta-lactam Dosing in Critically Ill Patients
Secondary ID [1] 0 0
TGI-CCT254643
Universal Trial Number (UTN)
Trial acronym
BLING III
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Continuous infusion
Other interventions - Intermittent infusion

Other: Continuous Infusion - The prescribed Beta-lactam is administered by a continuous infusion.

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


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

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

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All-cause mortality - Patient mortality status assessed at 90 days after randomisation
Timepoint [1] 0 0
90 Days after randomisation
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Day 14 post randomisation
Secondary outcome [2] 0 0
New acquisition, colonisation or infection - New acquisition, colonisation or infection with an Multi-resistant organism (MRO) or Clostridium difficile diarrhoea
Timepoint [2] 0 0
up to 14 days post randomisation or hospital discharge, whichever is sooner
Secondary outcome [3] 0 0
All cause ICU mortality - Patient mortality status assessed at ICU discharge
Timepoint [3] 0 0
up to 90 days
Secondary outcome [4] 0 0
All cause hospital mortality - Patient mortality status assessed at hospital discharge
Timepoint [4] 0 0
up to 90 days

Eligibility
Key inclusion criteria
1. Documented site of infection or strong suspicion of infection

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Age less than 18 years

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,TAS,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
St Vincents Hosptial - Darlinghurst
Recruitment hospital [4] 0 0
Gosford Hospital - Gosford
Recruitment hospital [5] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [6] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [7] 0 0
St George Hospital - Sydney
Recruitment hospital [8] 0 0
Westmead Hospital - Westmead
Recruitment hospital [9] 0 0
Royal Darwin Hospital - Casuarina
Recruitment hospital [10] 0 0
The Wesley Hospital - Auchenflower
Recruitment hospital [11] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [12] 0 0
Caboolture Hospital - Caboolture
Recruitment hospital [13] 0 0
Logan Hospital - Meadowbrook
Recruitment hospital [14] 0 0
Redcliffe Hospital - Redcliffe
Recruitment hospital [15] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [16] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [17] 0 0
The Queen Elizabeth Hospital - Adelaide
Recruitment hospital [18] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [19] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [20] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [21] 0 0
Bendigo Hospital - Bendigo
Recruitment hospital [22] 0 0
Box Hill Hospital - Eastern Health - Box Hill
Recruitment hospital [23] 0 0
Geelong University Hospital - Geelong
Recruitment hospital [24] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [25] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2250 - Gosford
Recruitment postcode(s) [5] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [6] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [7] 0 0
- Sydney
Recruitment postcode(s) [8] 0 0
2145 - Westmead
Recruitment postcode(s) [9] 0 0
0811 - Casuarina
Recruitment postcode(s) [10] 0 0
4066 - Auchenflower
Recruitment postcode(s) [11] 0 0
- Brisbane
Recruitment postcode(s) [12] 0 0
4510 - Caboolture
Recruitment postcode(s) [13] 0 0
4131 - Meadowbrook
Recruitment postcode(s) [14] 0 0
4020 - Redcliffe
Recruitment postcode(s) [15] 0 0
4215 - Southport
Recruitment postcode(s) [16] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [17] 0 0
- Adelaide
Recruitment postcode(s) [18] 0 0
5042 - Bedford Park
Recruitment postcode(s) [19] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [20] 0 0
7001 - Hobart
Recruitment postcode(s) [21] 0 0
3550 - Bendigo
Recruitment postcode(s) [22] 0 0
3128 - Box Hill
Recruitment postcode(s) [23] 0 0
3220 - Geelong
Recruitment postcode(s) [24] 0 0
3084 - Heidelberg
Recruitment postcode(s) [25] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Anderlecht
Country [2] 0 0
Belgium
State/province [2] 0 0
Chirec
Country [3] 0 0
Belgium
State/province [3] 0 0
Antwerpen
Country [4] 0 0
Belgium
State/province [4] 0 0
Antwerp
Country [5] 0 0
Belgium
State/province [5] 0 0
Brussels
Country [6] 0 0
Belgium
State/province [6] 0 0
Gent
Country [7] 0 0
Belgium
State/province [7] 0 0
Ottignies
Country [8] 0 0
France
State/province [8] 0 0
Bouche Du Rhone
Country [9] 0 0
France
State/province [9] 0 0
Gard
Country [10] 0 0
France
State/province [10] 0 0
Nimes
Country [11] 0 0
France
State/province [11] 0 0
Vaucluse
Country [12] 0 0
New Zealand
State/province [12] 0 0
Auckland
Country [13] 0 0
New Zealand
State/province [13] 0 0
Christchurch
Country [14] 0 0
New Zealand
State/province [14] 0 0
Hamilton
Country [15] 0 0
New Zealand
State/province [15] 0 0
Wellington
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Berkshire
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Brixton
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Bromley
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Buckinghamshire
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Cheshire
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Dorset
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Durham
Country [23] 0 0
United Kingdom
State/province [23] 0 0
East Suffolk
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Essex
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Gloucstershire
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Greater Manchester
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Hammersmith
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Hampshire
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Hertfordshire
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Kent
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Lancashire
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Northhumberland
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Northumberland
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Nottinghamshire
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Paddington
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Prescot
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Shepherds Bush
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Somerset
Country [40] 0 0
United Kingdom
State/province [40] 0 0
South Tees
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Surrey
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Tyne And Wear
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Wales
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Warwickshire
Country [45] 0 0
United Kingdom
State/province [45] 0 0
West Midlands
Country [46] 0 0
United Kingdom
State/province [46] 0 0
West Yorkshire
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Bristol
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Hull
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Australian and New Zealand Intensive Care Society Clinical Trials Group
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT03213990
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jeffrey Lipman
Address 0 0
The George Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Dorrilyn Rajbhandari
Address 0 0
Country 0 0
Phone 0 0
+61 410 530 548
Fax 0 0
Email 0 0
drajbhandari@georgeinstitute.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03213990