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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03869437




Registration number
NCT03869437
Ethics application status
Date submitted
6/02/2019
Date registered
11/03/2019
Date last updated
11/03/2019

Titles & IDs
Public title
RCT Cefiderocol vs BAT for Treatment of Gram Negative BSI
Scientific title
Investigator Driven Randomized Controlled Trial of Cefiderocol Versus Standard Therapy for Healthcare Associated and Hospital Acquired Gram-negative Blood Stream Infection: Study Protocol (the GAME CHANGER Trial)
Secondary ID [1] 0 0
GAME CHANGER
Universal Trial Number (UTN)
Trial acronym
GAMECHANGER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bloodstream Infections 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cefiderocol
Other interventions - Best Available Therapy

Experimental: Cefiderocol - Participants will receive Cefiderocol 2 g administered intravenously over 3 hours, every 8 hours for up to 14 days

Active Comparator: Best Available Therapy (BAT) - BAT will be chosen by the investigator and intravenously administered per country-specific guidelines


Treatment: Drugs: Cefiderocol
2 g intravenously over 3 hours every 8 hours for a period of 7 to 14 days (dosage adjustment is necessary based on renal function).

Other interventions: Best Available Therapy
Standard of care was determined by the investigator

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mortality at 14 days - To compare the 14-day mortality from day of randomisation of each regimen (cefiderocol versus standard of care therapy
Timepoint [1] 0 0
14 days post randomisation
Secondary outcome [1] 0 0
Mortality post blood stream infection of each regimen at longer time points - To compare the 30 and 90-day mortality from day of randomisation of each regimen (Cefiderocol versus standard of care therapy)
Timepoint [1] 0 0
30 & 90 days
Secondary outcome [2] 0 0
Functional outcome of patients treated with each regimen - Change of functional bacteremia outcome score from day of randomization to day 30.
Timepoint [2] 0 0
Day 30
Secondary outcome [3] 0 0
Clinical and microbiologic success - Defined as survival PLUS resolution of fever and leucocytosis PLUS sterilisation of blood cultures
Timepoint [3] 0 0
Day 14
Secondary outcome [4] 0 0
Microbiologic resolution of infection - Defined as sterility of blood cultures collected on or before day 7
Timepoint [4] 0 0
on or before study day 7
Secondary outcome [5] 0 0
Clostridium Difficile colitis - To compare the risk of Clostridium difficile colitis with each regime
Timepoint [5] 0 0
90 days post randomisation
Secondary outcome [6] 0 0
Microbiologic relapse - Defined as growth of a resistant Gram negative bacillus from any clinical specimen collected or a positive stool test (according to local lab diagnostic procedures) for C. difficile, from day 4 of study drug administration to day 30 and day 90
Timepoint [6] 0 0
30 and 90 days post randomisation
Secondary outcome [7] 0 0
Total number of participants with any serious adverse events (SAEs), and the cumulative incidence of SAEs - To compare the safety profile between standard of care and Cefiderocol
Timepoint [7] 0 0
At 30 and 90 days post randomisation
Secondary outcome [8] 0 0
Appropriateness of initial antibiotic therapy at enrolment (in vitro) - Defined as the organism isolated in blood culture testing susceptible to the antibiotic that the patient initially received. Susceptibility will be defined as per local laboratory protocol.
Timepoint [8] 0 0
14 days post randomisation
Secondary outcome [9] 0 0
Resource utilization required for the treatment of the study qualifying infection - To compare hospital length of stay (LOS), requirement of ICU admission and length of stay in ICU
Timepoint [9] 0 0
90 days post randomisation
Secondary outcome [10] 0 0
Risk of becoming colonised with a multidrug resistant organism - Colonisation with MRSA, VRE or a meropenem resistant Gram- negative organism (different from that in the original blood culture) during the 90 days from randomization
Timepoint [10] 0 0
90 days post randomisation

Eligibility
Key inclusion criteria
- Bloodstream infection with a Gram-negative organism from at least one blood culture
draw. Bacterial identification to species level will be performed using standard
laboratory methods (e.g. MALDI-TOF) and susceptibility testing (e.g. Vitek2).

- The blood stream infection fulfils the criteria as a hospital acquired or healthcare
associated infection as per the following definitions

- 1a Hospital acquired - Blood stream infection occurring greater than 48 hours after
hospital admission, assessed as symptoms or signs of infection not present at time of
hospital admission

- 1b Healthcare associated - Blood stream infection present at admission to hospital or
within 48 hours of admission in patients that fulfil ANY of following criteria

- 2a Patient has an intravascular catheter/line that is the source of infection

- 2b Attended a hospital or haemodialysis clinic or received intravenous chemotherapy in
the previous 30 days

- 2c were hospitalized in an acute care hospital for two or more days in the previous 90
days

- 2d resided in a nursing home or long-term care facility

- 2e received intravenous antibiotic therapy at home, wound care or specialized nursing
care through a healthcare agency, family or friends; or had self-administered
intravenous antibiotic medical therapy in the 30 days before the infection

- 1c OR patient meets the diagnosis of community acquired pneumonia where the
Gram-negative organism isolated is considered or proven to be the causative agent of
the pneumonia.

- No more than 36 hours has elapsed since the positive blood culture collection.

- Patient is aged 18 years and over (21 in Singapore)

- The patient or approved proxy is able to provide informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Refractory shock or comorbid condition such that patient not expected to survive more
than 7 days

- Patient with history of moderate to severe hypersensitivity reaction to a
cephalosporin

- Patient with Gram-positive bacteraemia including a significant Gram-positive pathogen
(a Gram-positive skin contaminant in one set of blood cultures may not regarded as
significant).

- Where the bloodstream infection is thought to be related to a vascular catheter and
the catheter is unable to be removed.

- Treatment is not with the intent to cure the infection (that is, palliative care is an
exclusion).

- Known pregnancy or breast-feeding.

- Patient is receiving peritoneal dialysis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [2] 0 0
Royal Brisbane and Womens Hospital - Brisbane
Recruitment hospital [3] 0 0
Monash Health - Melbourne
Recruitment hospital [4] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
Western Sydney Local Health District (Westmead Hospital) - Sydney
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Greece
State/province [1] 0 0
Athens
Country [2] 0 0
Italy
State/province [2] 0 0
Bologna
Country [3] 0 0
Singapore
State/province [3] 0 0
Singapore
Country [4] 0 0
Thailand
State/province [4] 0 0
Bangkok
Country [5] 0 0
Turkey
State/province [5] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Shionogi
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to determine whether a new antibiotic, Cefiderocol which works
against a wide variety of gram negative bacteria, is equally effective as the antibiotics
that are currently used as current standard of care.
Trial website
https://clinicaltrials.gov/show/NCT03869437
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Paterson, Professor
Address 0 0
The Univeristy of Queensland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Hugh Wright, Dr
Address 0 0
Country 0 0
Phone 0 0
+61 7 3346 5555
Fax 0 0
Email 0 0
gamechanger@uq.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03869437