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RecruitingNCT07004049TREAT-GNBUpdated Jun 4, 2025

Optimising TREATment for Severe Gram-Negative Bacterial Infections

A Phase 4 interventional study of Colistin/Polymyxin B + Sulbactam and Colistin/Polymyxin B + Tigecycline/Eravacycline in Bloodstream Infection, Ventilator Associated Bacterial Pneumonia and Hospital Acquired Bacterial Pneumonia, sponsored by National University of Singapore. Recruiting at 41 sites in 12 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-06-04.

Sponsored by National University of Singapore · Phase 4, Interventional, and Treatment

From the registry’s dates

  • Started Apr 2025; still recruiting 1 year 6 months later.
Phase
Phase 4
Study type
Interventional
Enrollment
600
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Bloodstream Infection
  • Ventilator Associated Bacterial Pneumonia
  • Hospital Acquired Bacterial Pneumonia
  • Carbapenem Resistant Bacterial Infection
  • Multidrug Resistance

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03

In context

Sepsis

2,416 studies on the registry are indexed under Sepsis; 541 are open to participants now.

This study's planned enrollment of 600 is above the median of 102 across 1,165 interventional studies indexed under Sepsis.

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Lead sponsor

National University of Singapore is the lead sponsor of 212 studies on the registry; 54 are open to participants now.

Browse National University of Singapore studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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).

Exclusion criteria

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
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Factorial assignment
Masking
None (open label)
Enrollment
600 participants (estimated)

Study arms

  • Active comparator
    Colistin/Polymyxin B + Sulbactam

    Drug: Colistin/Polymyxin B + Sulbactam

  • Active comparator
    Colistin/Polymyxin B + Tigecycline/Eravacycline

    Drug: Colistin/Polymyxin B + Tigecycline/Eravacycline

  • Active comparator
    Colistin/Polymyxin B + Meropenem

    Drug: Colistin/Polymyxin B + Meropenem

  • Active comparator
    Ceftazidime-avibactam + Sulbactam

    Drug: Ceftazidime-avibactam + Sulbactam

  • Active comparator
    Ceftazidime-avibactam + Fosfomycin

    Drug: Ceftazidime-avibactam + Fosfomycin

  • Active comparator
    Ceftazidime-avibactam

    Drug: Ceftazidime-avibactam

  • Active comparator
    Ceftazidime-avibactam + Aztreonam

    Drug: Ceftazidime-avibactam + Aztreonam

  • Active comparator
    Ceftazidime-avibactam + Colistin/Polymyxin B

    Drug: Ceftazidime-avibactam + Colistin/Polymyxin B

  • Active comparator
    High-dose meropenem

    Drug: High-dose meropenem

  • Active comparator
    Meropenem + Fosfomycin

    Drug: Meropenem + Fosfomycin

  • Active comparator
    Meropenem-vaborbactam

    Drug: Meropenem-vaborbactam

  • Active comparator
    Cefiderocol

    Drug: Cefiderocol

  • Active comparator
    Ceftolozane-tazobactam

    Drug: Ceftolozane-tazobactam

  • Active comparator
    Ceftolozane-tazobactam + Meropenem

    Drug: Ceftolozane-tazobactam + Meropenem

Interventions

  • DrugColistin/Polymyxin B + Sulbactam

    Drug pages: Colistin · Polymyxin B · Sulbactam

    For carbapenem-resistant Acinetobacter infections in China, Malaysia, Thailand and Singapore

  • DrugColistin/Polymyxin B + Tigecycline/Eravacycline

    Drug pages: Colistin · Polymyxin B · Tigecycline · Eravacycline

    For carbapenem-resistant Acintobacter, carbapenem-resistant Enterobacterales infections in China, Malaysia, Thailand and Singapore

  • DrugColistin/Polymyxin B + Meropenem

    Drug pages: Colistin · Polymyxin B · Meropenem

    For carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales infections in China, Malaysia and Singapore

  • DrugCeftazidime-avibactam + Sulbactam

    Drug page: Sulbactam

    For carbapenem-resistant Acinetobacter infections in China, Malaysia, Thailand, Singapore and Australia.

  • DrugCeftazidime-avibactam + Fosfomycin

    Drug page: Fosfomycin

    For carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales infections in Malaysia, Thailand and Singapore

  • DrugCeftazidime-avibactam

    For carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales infections in China, Malaysia, Thailand, Singapore, Europe and Australia.

  • DrugCeftazidime-avibactam + Aztreonam

    Drug page: Aztreonam

    For carbapenem-resistant Enterobacterales infections in China, Malaysia, Thailand, Singapore, Europe and Australia.

  • DrugCeftazidime-avibactam + Colistin/Polymyxin B

    Drug pages: Colistin · Polymyxin B

    For carbapenem-resistant Pseudomonas aeruginosa in China, Malaysia, Thailand, Singapore and Europe.

  • DrugHigh-dose meropenem

    For carbapenem-resistant Enterobacterales infection in Europe

  • DrugMeropenem + Fosfomycin

    Drug pages: Meropenem · Fosfomycin

    For carbapenem-resistant Enterobacterales in Europe

  • DrugMeropenem-vaborbactam

    For carbapenem-resistant Enterobacterales infection in Europe

  • DrugCefiderocol

    For carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales infections in Europe and Australia.

  • DrugCeftolozane-tazobactam

    For carbapenem-resistant Pseudomonas aeruginosa in Europe and Australia.

  • DrugCeftolozane-tazobactam + Meropenem

    Drug page: Meropenem

    For carbapenem-resistant Pseudomonas aeruginosa in Europe.

06

What researchers measure

Primary outcomes

  1. Clinical outcome

    28-day all-cause mortality after randomisation

    Time frame: 28 days post-randomisation

Secondary outcomes

  1. Clinical outcome

    All-cause mortality at 14, 60 and 90 days after randomisation

    Time frame: 14, 60 and 90 days post-randomisation

  2. Clinical outcome

    Proportion of patients with infection relapse or reinfection within 90 days after randomisation

    Time frame: 90 days post-randomisation

  3. Clinical outcome

    Length of mechanical ventilation in the intensive care within 28 days after randomisation

    Time frame: 28 days post-randomisation

  4. Clinical outcome

    All cause re-admission into an acute care hospital within 90 days after randomisation

    Time frame: 90 days post-randomisation

  5. Clinical outcome

    Proportion of patients that develop Kidney Disease Improving Global Outcomes (KDIGO) acute kidney injury within 28 days after randomisation

    Time frame: 28 days post-randomisation

  6. Clinical outcome

    Proportion of patients that develop Clostridioides difficile or antibiotic-related diarrhea within 28 days after randomisation

    Time frame: 28 days post-randomisation

  7. Clinical outcome

    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

    Time frame: 28 and 90 days post-randomisation

  8. Clinical outcome

    Composite outcome measure defined by Desirability of Outcome Ranking (DOOR) at 28 days after randomisation

    Time frame: 28 days post-randomisation

  9. Clinical outcome

    Sequential Organ Failure Assessment (SOFA) Score (0 to 24) improvement between baseline and 14 days after randomisation

    Time frame: 14 days post-randomisation

  10. Clinical outcome

    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)

    Time frame: 14 days post-randomisation

  11. Clinical outcome

    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)

    Time frame: 14, 28 and 90 days post-randomisation

  12. Health economics outcomes

    Length of continuous stay in the intensive care from the hospital which the participant was recruited within 28 days after randomisation

    Time frame: 28 days post-randomisation

  13. Health economics outcomes

    Length of continuous stay in the hospital which the participant was recruited within 28 days after randomisation

    Time frame: 28 days post-randomisation

  14. Health economics outcomes

    Days of antibiotic use within 28 days after randomisation

    Time frame: 28 days post-randomisation

  15. Health economics outcomes

    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/)

    Time frame: 28 and 90 days post-randomisation

07

Study locations

1 of 41 sites recruiting
08

References and documents

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. PubMed 31866328 ↗
  • 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. PubMed 30535100 ↗
  • 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. PubMed 31654791 ↗
  • 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. PubMed 26113652 ↗
  • 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. PubMed 33894130 ↗

Individual participant data

Plan to share: Yes — De-identified patient data

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Apr 2025 (actual). Primary completion is estimated for Dec 2028, 44 months after the start.

Of 65 non-industry phase 4 interventional studies under Sepsis, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 15 and three quarters within 45. This study's planned 44 months is above that.

Counting every sponsor, half of 66 studies reached it within 25 months; a quarter within 15 and three quarters within 43.

How these figures are worked out, and which studies are left out of them.

Registered
Apr 29, 2025
First posted
Jun 4, 2025
StartActual
Apr 21, 2025
Primary completionEst.
Dec 31, 2028
CompletionEst.
Dec 31, 2028
Last update
Jun 4, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 4, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07004049
Lead sponsor
National University of Singapore
Collaborators
The University of Queensland, European Clinical Research Alliance for Infectious Diseases (ECRAID)
Responsible party
Mo Yin (Consultant / Adjunct Assistant Professor, National University of Singapore) — Principal investigator
First posted
Jun 4, 2025
Start date
Apr 21, 2025
Primary completion
Dec 31, 2028 (estimated)
Completion
Dec 31, 2028 (estimated)
Last update
Jun 4, 2025

Study contacts

Yin Mo, MBBS, PhD
Contact
mdcmy@nus.edu.sg
+65 65164988

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Colistin · Polymyxin B · Sulbactam · Tigecycline · Eravacycline · Meropenem · Fosfomycin · Aztreonam · Meropenem and vaborbactam · Cefiderocol

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