Optimising treatment for severe Gram-negative infections

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• National University Hospital
  Singapore, Singapore, Singapore Recruiting
• Royal Brisbane and Women's Hospital
  Brisbane, Queensland, Australia Not yet recruiting
• Princess Alexandra Hospital
  Brisbane, Australia Not yet recruiting
• The First Affiliated Hospital, Zhejiang University School of Medicine
  Hangzhou, China Not yet recruiting
• The Second Affiliated Hospital, Xi'an Jiang Tong University
  Xi'an, China Not yet recruiting
• Xuzhou First People's Hospital
  Xuzhou, China Not yet recruiting

Study contacts

• Study coordinator: Yin Mo, MBBS, PhD
• Email: mdcmy@nus.edu.sg
• Phone: +65 65164988

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Assessing the safety and effectiveness of OMN6 for pneumonia caused by Acinetobacter baumannii

  This study is testing a new drug called OMN6 to see if it can safely help people with pneumonia caused by a specific bacteria called Acinetobacter baumannii.

  Recruiting at 15 sites Phase 2 Omnix Medical Ltd · Athens and 14 other locations · NCT06087536

• Oral switch for bloodstream infections in immunocompromised children

  This trial tests whether switching from IV to oral antibiotics is just as safe as continuing IV therapy for children with bloodstream infections who are immunocompromised or have a central venous catheter.

  Recruiting at 4 sites Phase 4 Copenhagen University Hospital, Rigshospitalet · Aalborg and 3 other locations · NCT07923266

• Middle East study of bloodstream infections in blood cancer patients and HSCT recipients

  This is an observational study to see how bloodstream infections affect adults with blood cancers or after stem cell transplants across several Middle East countries.

  Recruiting at 9 sites Hamad Medical Corporation · Amman and 8 other locations · NCT07900542

• Oral switch for kids with bloodstream infections after starting IV therapy

  This trial will test whether switching from IV to oral antibiotics early is not worse than continuing IV treatment for previously healthy children and teens with uncomplicated bloodstream infections.

  Recruiting at 18 sites Phase 4 Copenhagen University Hospital, Rigshospitalet · Aabenraa and 17 other locations · NCT07791914

• Sulbactam-Durlobactam for CRAB infections in real-world care

  This real-world study tests whether sulbactam-durlobactam works and is safe for adults with carbapenem-resistant Acinetobacter baumannii infections, compared with other anti-CRAB treatments.

  Recruiting Sichuan Provincial People's Hospital · Chengdu, Sichuan · NCT07601711

• Fast antibiotic sensitivity tests to guide treatment for bloodstream infections

  This tests whether rapid antibiotic susceptibility tests can help doctors pick the right antibiotics sooner for adults with positive blood cultures and improve recovery and antibiotic use.

  Recruiting Istituto Clinico Humanitas · Rozzano, Milan · NCT07491419

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.