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Optimising treatment for severe Gram-negative infections

TREAT-GNB [CR-GNB]

Phase 4 Interventional National University of Singapore · NCT07004049

This tests different antibiotic combinations to see if they improve 28-day survival for people with severe multidrug-resistant Gram-negative bloodstream or lower-respiratory infections.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years and up
SexAll
SponsorNational University of Singapore Academic / other
Locations41 sites (Brisbane, Queensland and 40 other locations)
Trial IDNCT07004049 on ClinicalTrials.gov

What this trial studies

TREAT-GNB is a platform, adaptive, phase 4 interventional programme that randomises hospitalized patients with severe carbapenem-resistant or multidrug-resistant Gram-negative bloodstream infections or ventilator- or hospital-acquired pneumonia to one of several antibiotic combination regimens. The CR-GNB silo compares multiple regimens (for example colistin/polymyxin B combined with sulbactam, tigecycline/eravacycline, or meropenem, and ceftazidime-avibactam combined with sulbactam or fosfomycin) with allocation determined by site-specific randomisation lists. The primary outcome is all-cause mortality at 28 days, and the adaptive design allows ineffective arms to be dropped and promising options to be prioritised to streamline resource use. Eligible patients are those with recent positive blood cultures or CDC-defined ventilator-/hospital-acquired pneumonia who are suitable for at least two of the site's available regimens and can be randomised within about 96 hours of sampling.

Who should consider this trial

Good fit: Ideal candidates are hospitalized adults with culture-proven Gram-negative bloodstream infection or ventilator-/hospital-acquired pneumonia due to suspected or confirmed carbapenem-resistant organisms who can receive at least two of the trial's antibiotic options within about 96 hours of sample collection.

Not a fit: Patients without Gram-negative infections, with organisms clearly susceptible to standard first-line antibiotics, those not eligible for at least two regimens, or those presenting too late after sample collection (>96 hours) may not receive benefit from participation.

Why it matters

Potential benefit: If successful, the platform could identify antibiotic combinations that reduce 28-day deaths and provide clearer treatment guidance for severe carbapenem-resistant Gram-negative infections.

How similar studies have performed: Some individual antibiotics and combination regimens (for example ceftazidime-avibactam) have shown benefit in prior trials or series, but applying a multi-arm adaptive platform specifically for CR-GNB is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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:
   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

Where this trial is running

Brisbane, Queensland and 40 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Bloodstream InfectionVentilator Associated Bacterial PneumoniaHospital Acquired Bacterial PneumoniaCarbapenem Resistant Bacterial InfectionMultidrug Resistance
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.