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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT07004049
Registration number
NCT07004049
Ethics application status
Date submitted
29/04/2025
Date registered
4/06/2025
Date last updated
4/06/2025
Titles & IDs
Public title
Optimising TREATment for Severe Gram-Negative Bacterial Infections
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Scientific title
TREAT-GNB [CR-GNB]
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Secondary ID [1]
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ADVANCE-ID 24003
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Universal Trial Number (UTN)
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Trial acronym
TREAT-GNB
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Bloodstream Infection
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Ventilator Associated Bacterial Pneumonia
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Hospital Acquired Bacterial Pneumonia
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Carbapenem Resistant Bacterial Infection
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Multidrug Resistance
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Condition category
Condition code
Infection
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0
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Studies of infection and infectious agents
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Infection
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Other infectious diseases
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Infection
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Sexually transmitted infections
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Respiratory
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Other respiratory disorders / diseases
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Inflammatory and Immune System
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0
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Other inflammatory or immune system disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Colistin/Polymyxin B + Sulbactam
Treatment: Drugs - Colistin/Polymyxin B + Tigecycline/Eravacycline
Treatment: Drugs - Colistin/Polymyxin B + Meropenem
Treatment: Drugs - Ceftazidime-avibactam + Sulbactam
Treatment: Drugs - Ceftazidime-avibactam + Fosfomycin
Treatment: Drugs - Ceftazidime-avibactam
Treatment: Drugs - Ceftazidime-avibactam + Aztreonam
Treatment: Drugs - Ceftazidime-avibactam + Colistin/Polymyxin B
Treatment: Drugs - High-dose meropenem
Treatment: Drugs - Meropenem + Fosfomycin
Treatment: Drugs - Meropenem-vaborbactam
Treatment: Drugs - Cefiderocol
Treatment: Drugs - Ceftolozane-tazobactam
Treatment: Drugs - Ceftolozane-tazobactam + Meropenem
Active comparator: Colistin/Polymyxin B + Sulbactam -
Active comparator: Colistin/Polymyxin B + Tigecycline/Eravacycline -
Active comparator: Colistin/Polymyxin B + Meropenem -
Active comparator: Ceftazidime-avibactam + Sulbactam -
Active comparator: Ceftazidime-avibactam + Fosfomycin -
Active comparator: Ceftazidime-avibactam -
Active comparator: Ceftazidime-avibactam + Aztreonam -
Active comparator: Ceftazidime-avibactam + Colistin/Polymyxin B -
Active comparator: High-dose meropenem -
Active comparator: Meropenem + Fosfomycin -
Active comparator: Meropenem-vaborbactam -
Active comparator: Cefiderocol -
Active comparator: Ceftolozane-tazobactam -
Active comparator: Ceftolozane-tazobactam + Meropenem -
Treatment: Drugs: Colistin/Polymyxin B + Sulbactam
For carbapenem-resistant Acinetobacter infections in China, Malaysia, Thailand and Singapore
Treatment: Drugs: Colistin/Polymyxin B + Tigecycline/Eravacycline
For carbapenem-resistant Acintobacter, carbapenem-resistant Enterobacterales infections in China, Malaysia, Thailand and Singapore
Treatment: Drugs: Colistin/Polymyxin B + Meropenem
For carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales infections in China, Malaysia and Singapore
Treatment: Drugs: Ceftazidime-avibactam + Sulbactam
For carbapenem-resistant Acinetobacter infections in China, Malaysia, Thailand, Singapore and Australia.
Treatment: Drugs: Ceftazidime-avibactam + Fosfomycin
For carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales infections in Malaysia, Thailand and Singapore
Treatment: Drugs: Ceftazidime-avibactam
For carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales infections in China, Malaysia, Thailand, Singapore, Europe and Australia.
Treatment: Drugs: Ceftazidime-avibactam + Aztreonam
For carbapenem-resistant Enterobacterales infections in China, Malaysia, Thailand, Singapore, Europe and Australia.
Treatment: Drugs: Ceftazidime-avibactam + Colistin/Polymyxin B
For carbapenem-resistant Pseudomonas aeruginosa in China, Malaysia, Thailand, Singapore and Europe.
Treatment: Drugs: High-dose meropenem
For carbapenem-resistant Enterobacterales infection in Europe
Treatment: Drugs: Meropenem + Fosfomycin
For carbapenem-resistant Enterobacterales in Europe
Treatment: Drugs: Meropenem-vaborbactam
For carbapenem-resistant Enterobacterales infection in Europe
Treatment: Drugs: Cefiderocol
For carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales infections in Europe and Australia.
Treatment: Drugs: Ceftolozane-tazobactam
For carbapenem-resistant Pseudomonas aeruginosa in Europe and Australia.
Treatment: Drugs: Ceftolozane-tazobactam + Meropenem
For carbapenem-resistant Pseudomonas aeruginosa in Europe.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Clinical outcome
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Assessment method [1]
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28-day all-cause mortality after randomisation
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Timepoint [1]
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28 days post-randomisation
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Secondary outcome [1]
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Clinical outcome
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Assessment method [1]
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All-cause mortality at 14, 60 and 90 days after randomisation
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Timepoint [1]
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14, 60 and 90 days post-randomisation
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Secondary outcome [2]
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Clinical outcome
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Assessment method [2]
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Proportion of patients with infection relapse or reinfection within 90 days after randomisation
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Timepoint [2]
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90 days post-randomisation
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Secondary outcome [3]
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Clinical outcome
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Assessment method [3]
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Length of mechanical ventilation in the intensive care within 28 days after randomisation
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Timepoint [3]
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28 days post-randomisation
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Secondary outcome [4]
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Clinical outcome
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Assessment method [4]
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All cause re-admission into an acute care hospital within 90 days after randomisation
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Timepoint [4]
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90 days post-randomisation
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Secondary outcome [5]
0
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Clinical outcome
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Assessment method [5]
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Proportion of patients that develop Kidney Disease Improving Global Outcomes (KDIGO) acute kidney injury within 28 days after randomisation
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Timepoint [5]
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28 days post-randomisation
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Secondary outcome [6]
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Clinical outcome
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Assessment method [6]
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Proportion of patients that develop Clostridioides difficile or antibiotic-related diarrhea within 28 days after randomisation
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Timepoint [6]
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28 days post-randomisation
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Secondary outcome [7]
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Clinical outcome
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Assessment method [7]
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Proportion of participants who have returned to their usual level of function at day 28 and 90 as determined by whether the modified functional bloodstream infection score (FBIS) remained the same or improved from baseline
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Timepoint [7]
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28 and 90 days post-randomisation
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Secondary outcome [8]
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Clinical outcome
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Assessment method [8]
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Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) at 28 days after randomisation
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Timepoint [8]
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28 days post-randomisation
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Secondary outcome [9]
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Clinical outcome
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Assessment method [9]
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Sequential Organ Failure Assessment (SOFA) Score (0 to 24) improvement between baseline and 14 days after randomisation
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Timepoint [9]
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14 days post-randomisation
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Secondary outcome [10]
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Clinical outcome
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Assessment method [10]
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Clinical response at 14 days after randomisation (Binary outcome: Improved or not improved, determined using 1. Temperature \< 38°C for 48hours, and 2. Systolic blood pressure \>90mmHg without inotropes)
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Timepoint [10]
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14 days post-randomisation
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Secondary outcome [11]
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Clinical outcome
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Assessment method [11]
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Clinical cure at 14, 28 and 90 days after randomisation (binary outcome: cure or no cure, as defined in the INHALE trial for VAP/HAP and in Yahav et al. trial for BSI)
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Timepoint [11]
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14, 28 and 90 days post-randomisation
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Secondary outcome [12]
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Health economics outcomes
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Assessment method [12]
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Length of continuous stay in the intensive care from the hospital which the participant was recruited within 28 days after randomisation
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Timepoint [12]
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28 days post-randomisation
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Secondary outcome [13]
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Health economics outcomes
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Assessment method [13]
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Length of continuous stay in the hospital which the participant was recruited within 28 days after randomisation
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Timepoint [13]
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28 days post-randomisation
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Secondary outcome [14]
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Health economics outcomes
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Assessment method [14]
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Days of antibiotic use within 28 days after randomisation
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Timepoint [14]
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28 days post-randomisation
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Secondary outcome [15]
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Health economics outcomes
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Assessment method [15]
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Functional outcome at 28 and 90 days after randomisation (measured using EQ-5D-3L: https://euroqol.org/information-and-support/euroqol-instruments/eq-5d-3l/)
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Timepoint [15]
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28 and 90 days post-randomisation
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Eligibility
Key inclusion criteria
A: Bloodstream infections
a) Suitable for at least 2 antibiotic regimens in the site randomisation list
1. Growth of Gram-negative bacilli identified from blood culture(s)
2. Receiving or planning to receive intravenous antibiotics
3. Expected time from blood culture sampling to randomisation is = 96 hours.
OR
B: Ventilator-associated pneumonia / hospital-acquired pneumonia a) Suitable for at least 2 antibiotic regimens in the site randomisation list b) Infection syndrome definitions^( (US Centers for Disease Control and Prevention National Healthcare Safety Network)3: i) At least one of the following:
1. temperature > 38 °C
2. white blood cell count = 12,000 cells/mm3 (12 x 109/L, 12 x 103/µL) or = 4,000 cells/mm3 (4 x 109/L, 4 x 103/µL)
3. altered mental status with no other causes in > 70 years old; AND ii) Two or more chest imaging tests demonstrating at least one of the following:
1) new and progressive OR progressive and persistent infiltrate 2) new and persistent OR progressive and persistent consolidation 3) new and persistent OR progressive and persistent cavitation; AND iii) At least two of the following:
1. new onset of purulent sputum, or change in character of sputum, or increased respiratory secretions, or increased in suctioning requirements
2. new onset or worsening tachypnoea or dyspnoea
3. rales or bronchial breath sounds
4. worsening gas exchange defined by oxygen desaturations (e.g., PaO2/FiO2 < 240), increased oxygen requirements or increased ventilation demand.
c) Hospital admission > 48 hours d) Predominant growth of Gram-negative bacilli identified from respiratory tract specimen(s)*; e) Receiving or planning to receive intravenous antibiotics f) Expected time from respiratory culture sampling to randomisation is = 96 hours
AND
C: CR-GNB antibiotic backbone domain
a) Gram-negative bacilli belonging to Acinetobacter baumannii-calcoaceticus complex, Pseudomonas aeruginosa or Enterobacterales b) Carbapenem resistance in isolate detected - i) Phenotypically via conventional microbiology testing: meropenem / imipenem / ertapenem resistance; OR ii) Genotypically via PCR or next generation sequencing: presence of genes associated with carbapenemase production (eg. blaNDM, blaKPC, blaIMP, blaIMI, blaVIM, blaOXA-48-like).
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Treating team deems enrolment in the study is not in the best interest of the patient
2. Patient is on end-of-life care
3. Patient is incarcerated in a correctional facility
4. Participation in any interventional study activities outlined in the TREAT-GNB study within the last 90 days
5. Pregnant women and children
OR
6. Polymicrobial bloodstream infection
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Factorial
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
21/04/2025
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/12/2028
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Actual
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Sample size
Target
600
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
QLD
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Recruitment hospital [1]
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Royal Brisbane and Women's Hospital - Brisbane
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Recruitment hospital [2]
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Princess Alexandra Hospital - Brisbane
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Recruitment postcode(s) [1]
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4006 - Brisbane
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Recruitment postcode(s) [2]
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- Brisbane
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Recruitment outside Australia
Country [1]
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China
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State/province [1]
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Hangzhou
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Country [2]
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China
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State/province [2]
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Xi'an
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China
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Xuzhou
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Lebanon
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Beirut
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Country [5]
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Malaysia
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State/province [5]
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Sabah
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Country [6]
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Malaysia
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State/province [6]
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Sarawak
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0
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Malaysia
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State/province [7]
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Selangor
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Qatar
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Doha
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Saudi Arabia
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Riyadh
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Singapore
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State/province [10]
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Singapore
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South Africa
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Johannesburg
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Spain
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State/province [12]
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Alicante
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0
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Spain
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State/province [13]
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Badajoz
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0
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Spain
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State/province [14]
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Barakaldo
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0
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Spain
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State/province [15]
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Barcelona
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Country [16]
0
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Spain
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Córdoba
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Spain
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Granada
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Pontevedra
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Spain
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San Sebastián
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Spain
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Santander
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Spain
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Seville
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Spain
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State/province [24]
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Zaragoza
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Country [25]
0
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Thailand
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Bangkok
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Country [26]
0
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Thailand
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State/province [26]
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Chiang Mai
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Country [27]
0
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Turkey
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State/province [27]
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Istanbul
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Country [28]
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United Arab Emirates
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State/province [28]
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Dubai
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Funding & Sponsors
Primary sponsor type
Other
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Name
National University of Singapore
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Address
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Other collaborator category [1]
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Other
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Name [1]
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The University of Queensland
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Address [1]
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Other collaborator category [2]
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Other
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Name [2]
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European Clinical Research Alliance for Infectious Diseases (ECRAID)
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Address [2]
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Ethics approval
Ethics application status
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Summary
Brief summary
TREAT-GNB is an innovative trial to expedite the evaluation of various antibiotic choices and treatment strategies for severe multidrug-resistant Gram-negative bacterial infections, specifically bloodstream and lower respiratory tract infections. This approach combines platform trial elements with adaptive clinical designs to streamline the evaluation of various treatment options and optimise resource utilisation. The overall aim of the TREAT-GNB platform trial is to identify interventions that improve survival in patients with severe infections due to Gram-negative bacteria. In the CR-GNB silo of TREAT-GNB, the primary objective is to quantify the effect on all-cause mortality at 28 days of a range of interventions in patients with bloodstream infections, ventilator-associated pneumonia, and hospital-acquired pneumonia caused by CR-GNB.
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Trial website
https://clinicaltrials.gov/study/NCT07004049
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Trial related presentations / publications
Niederman MS, Alder J, Bassetti M, Boateng F, Cao B, Corkery K, Dhand R, Kaye KS, Lawatscheck R, McLeroth P, Nicolau DP, Wang C, Wood GC, Wunderink RG, Chastre J. Inhaled amikacin adjunctive to intravenous standard-of-care antibiotics in mechanically ventilated patients with Gram-negative pneumonia (INHALE): a double-blind, randomised, placebo-controlled, phase 3, superiority trial. Lancet Infect Dis. 2020 Mar;20(3):330-340. doi: 10.1016/S1473-3099(19)30574-2. Epub 2019 Dec 19. Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M; Bacteremia Duration Study Group. Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial. Clin Infect Dis. 2019 Sep 13;69(7):1091-1098. doi: 10.1093/cid/ciy1054. McNamara JF, Harris PNA, Chatfield MD, Lorenc P, Paterson DL. Measuring patient-centred long-term outcome following a bloodstream infection: a pilot study. Clin Microbiol Infect. 2020 Feb;26(2):257.e1-257.e4. doi: 10.1016/j.cmi.2019.10.011. Epub 2019 Oct 23. Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D, Chuang-Stein C, Cosgrove SE, Fowler VG Jr, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015 Sep 1;61(5):800-6. doi: 10.1093/cid/civ495. Epub 2015 Jun 25. Walker AS, White IR, Turner RM, Hsu LY, Yeo TW, White NJ, Sharland M, Thwaites GE. Personalised randomised controlled trial designs-a new paradigm to define optimal treatments for carbapenem-resistant infections. Lancet Infect Dis. 2021 Jun;21(6):e175-e181. doi: 10.1016/S1473-3099(20)30791-X. Epub 2021 Apr 21.
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Public notes
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Contacts
Principal investigator
Name
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Address
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Fax
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Email
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Contact person for public queries
Name
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Yin Mo, MBBS, PhD
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Address
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Country
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Phone
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+65 65164988
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Data sharing statement
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT07004049
Download to PDF