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Optimising TREATment for Seve...

Optimising TREATment for Severe Gram-Negative Bacterial Infections

Last Updated: 2025-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-21

Study Completion Date

2028-12-31

Brief Summary

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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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Detailed Description

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

The backbone domain is a multi-arm antibiotic treatment intervention with a personalisable randomisation list. It adopts the "Personalised Randomised Controlled Trial" (PRACTical) design, which allows each participant to be randomised between a personalised randomisation list of treatments that are suitable for them. Each patient randomisation list ("personalised randomisation list") may be tailored based on their kidney function, pathogen genotype, pathogen antibiotic susceptibility and physician preference. Potential participants may be enrolled and randomised if they are eligible for at least two antibiotic options in the site randomisation list.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Colistin/Polymyxin B + Sulbactam

Group Type ACTIVE_COMPARATOR

Colistin/Polymyxin B + Sulbactam

Intervention Type DRUG

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

Colistin/Polymyxin B + Tigecycline/Eravacycline

Group Type ACTIVE_COMPARATOR

Colistin/Polymyxin B + Tigecycline/Eravacycline

Intervention Type DRUG

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

Colistin/Polymyxin B + Meropenem

Group Type ACTIVE_COMPARATOR

Colistin/Polymyxin B + Meropenem

Intervention Type DRUG

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

Ceftazidime-avibactam + Sulbactam

Group Type ACTIVE_COMPARATOR

Ceftazidime-avibactam + Sulbactam

Intervention Type DRUG

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

Ceftazidime-avibactam + Fosfomycin

Group Type ACTIVE_COMPARATOR

Ceftazidime-avibactam + Fosfomycin

Intervention Type DRUG

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

Ceftazidime-avibactam

Group Type ACTIVE_COMPARATOR

Ceftazidime-avibactam

Intervention Type DRUG

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

Ceftazidime-avibactam + Aztreonam

Group Type ACTIVE_COMPARATOR

Ceftazidime-avibactam + Aztreonam

Intervention Type DRUG

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

Ceftazidime-avibactam + Colistin/Polymyxin B

Group Type ACTIVE_COMPARATOR

Ceftazidime-avibactam + Colistin/Polymyxin B

Intervention Type DRUG

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

High-dose meropenem

Group Type ACTIVE_COMPARATOR

High-dose meropenem

Intervention Type DRUG

For carbapenem-resistant Enterobacterales infection in Europe

Meropenem + Fosfomycin

Group Type ACTIVE_COMPARATOR

Meropenem + Fosfomycin

Intervention Type DRUG

For carbapenem-resistant Enterobacterales in Europe

Meropenem-vaborbactam

Group Type ACTIVE_COMPARATOR

Meropenem-vaborbactam

Intervention Type DRUG

For carbapenem-resistant Enterobacterales infection in Europe

Cefiderocol

Group Type ACTIVE_COMPARATOR

Cefiderocol

Intervention Type DRUG

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

Ceftolozane-tazobactam

Group Type ACTIVE_COMPARATOR

Ceftolozane-tazobactam

Intervention Type DRUG

For carbapenem-resistant Pseudomonas aeruginosa in Europe and Australia.

Ceftolozane-tazobactam + Meropenem

Group Type ACTIVE_COMPARATOR

Ceftolozane-tazobactam + Meropenem

Intervention Type DRUG

For carbapenem-resistant Pseudomonas aeruginosa in Europe.

Interventions

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Colistin/Polymyxin B + Sulbactam

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

Intervention Type DRUG

Colistin/Polymyxin B + Tigecycline/Eravacycline

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

Intervention Type DRUG

Colistin/Polymyxin B + Meropenem

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

Intervention Type DRUG

Ceftazidime-avibactam + Sulbactam

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

Intervention Type DRUG

Ceftazidime-avibactam + Fosfomycin

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

Intervention Type DRUG

Ceftazidime-avibactam

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

Intervention Type DRUG

Ceftazidime-avibactam + Aztreonam

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

Intervention Type DRUG

Ceftazidime-avibactam + Colistin/Polymyxin B

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

Intervention Type DRUG

High-dose meropenem

For carbapenem-resistant Enterobacterales infection in Europe

Intervention Type DRUG

Meropenem + Fosfomycin

For carbapenem-resistant Enterobacterales in Europe

Intervention Type DRUG

Meropenem-vaborbactam

For carbapenem-resistant Enterobacterales infection in Europe

Intervention Type DRUG

Cefiderocol

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

Intervention Type DRUG

Ceftolozane-tazobactam

For carbapenem-resistant Pseudomonas aeruginosa in Europe and Australia.

Intervention Type DRUG

Ceftolozane-tazobactam + Meropenem

For carbapenem-resistant Pseudomonas aeruginosa in Europe.

Intervention Type DRUG

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Mo Yin

Consultant / Adjunct Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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