Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT03869437
Registration number
NCT03869437
Ethics application status
Date submitted
6/02/2019
Date registered
11/03/2019
Date last updated
13/02/2024
Titles & IDs
Public title
RCT Cefiderocol vs BAT for Treatment of Gram Negative BSI
Query!
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)
Query!
Secondary ID [1]
0
0
GAME CHANGER
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
GAMECHANGER
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Bloodstream Infections
0
0
Query!
Condition category
Condition code
Infection
0
0
0
0
Query!
Studies of infection and infectious agents
Query!
Infection
0
0
0
0
Query!
Other infectious diseases
Query!
Inflammatory and Immune System
0
0
0
0
Query!
Other inflammatory or immune system disorders
Query!
Intervention/exposure
Study type
Interventional
Query!
Description of intervention(s) / exposure
Treatment: Drugs - Cefiderocol
Other interventions - Best Available Therapy
Experimental: Cefiderocol - Participants will receive Cefiderocol 2 grams administered intravenously over 3 hours, every 8 hours for a minium of 5 days and a maximun of 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 grams intravenously administered over 3 hours every 8 hours for a period of 5 to 14 days (dosage adjustment is necessary based on renal function).
Other interventions: Best Available Therapy
Standard of care was determined by the investigator
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Intervention code [2]
0
0
Other interventions
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Mortality at 14 days
Query!
Assessment method [1]
0
0
To compare the 14-day mortality from day of randomisation of each regimen (cefiderocol versus standard of care therapy). If the primary objective meets the criteria for non-inferiority (with a margin of 10% for the difference in proportions), superiority will be examined.
Query!
Timepoint [1]
0
0
14 days post date of randomisation
Query!
Secondary outcome [1]
0
0
Mortality post blood stream infection of each regimen at longer time points
Query!
Assessment method [1]
0
0
If a date of death is recorded on or before our calculation of Day 14, the participant will be classed as dead, otherwise considered to be alive. Similar for Day 30. Where possible this rule will also be applied for Day 90 vital status. If the Day 90 follow-up actually occurred on day 85 to 89 and the participant was alive we will assume the participant was alive at day 90.
Query!
Timepoint [1]
0
0
30 and 90 days, from day of randomisation or "day 1"
Query!
Secondary outcome [2]
0
0
Clinical and microbiological failure at day 14
Query!
Assessment method [2]
0
0
Defined as composite of:
Death
Still in hospital and clinical failure, as de?ned by
If baseline SOFA =3, D(day)14 SOFA not improved by =30%
If baseline SOFA <3, D14 SOFA worse
Microbiological failure (GNB Growth in blood of same species as index GNB from days 3-14)
The SOFA score we will calculate is a slight modi?cation of the original SOFA score. It will be used for ICU and non-ICU participants. The sole modi?cation is that the respiratory component will be scored as in the modi?ed SOFA:
0 (if SaO2/FiO2 >400)
1 (if SaO2/FiO2 315-400)
2 (if SaO2/FiO2 235-314)
3 (if SaO2/FiO2 150-234)
4 (if SaO2/FiO2 <150)
Query!
Timepoint [2]
0
0
Day 14, from day of randomisation or "day 1"
Query!
Secondary outcome [3]
0
0
Microbiological failure days 3 to 90 post randomisation
Query!
Assessment method [3]
0
0
De?ned as growth in blood cultures of the same GNB as the index blood culture(s), from day 3 up to day 90.
Query!
Timepoint [3]
0
0
Day 3 through to day 90
Query!
Secondary outcome [4]
0
0
Colonisation or infection with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Gram-negative bacilli or Candida bloodstream infection.
Query!
Assessment method [4]
0
0
De?ned as the presence of MRSA, VRE or carbapenem-resistant Gram-negative bacilli (of a di?erent species from primary BSI organism) on culture +/- molecular test of clinical samples or screening swabs, or Candida species grown in blood cultures from day 3 up to day 90.
Query!
Timepoint [4]
0
0
Day 3 through to day 90
Query!
Secondary outcome [5]
0
0
Clostridioides di?cile infection days 3 to 90 post randomisation.
Query!
Assessment method [5]
0
0
De?ned as presence of a compatible clinical illness with a positive laboratory stool test for C. di?cile (as per local diagnostic protocol / method).
Query!
Timepoint [5]
0
0
Day 3 through to day 90
Query!
Secondary outcome [6]
0
0
Improvement in functional status at day 30 post randomisation compared to baseline.
Query!
Assessment method [6]
0
0
Functional status will be measured according to a score ranging from 0 (dead) to 7 (out of hospital, healthy, able to complete daily actvities). This score is based on the Functional Bloodstream Infection Score (FBIS) [McNamara et al. Clin Microbiol Infect. 2020 Feb;26(2):257.e1-257].
Query!
Timepoint [6]
0
0
Day 30, from day of randomisation or "day 1"
Query!
Secondary outcome [7]
0
0
Time to hospital discharge.
Query!
Assessment method [7]
0
0
De?ned as to the day of ?rst discharge alive (e.g. Day 2 is the day after randomisation). However, if a participant dies in the 3 days following ?rst hospital discharge, we will consider that participant as not having a discharge alive.
Query!
Timepoint [7]
0
0
From day of randomisation or "day 1" through to day 90
Query!
Secondary outcome [8]
0
0
Treatment emergent SAEs (Serious Adverse Events)
Query!
Assessment method [8]
0
0
Defined as a serious adverse event possibly, probably or definitely related to the randomised drug treatment.
Query!
Timepoint [8]
0
0
From day of randomisation or "day 1" through to 5 days post end of study treatment.
Query!
Eligibility
Key inclusion criteria
1. 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).
2. The blood stream infection fulfils the criteria as a hospital acquired or healthcare
associated infection as per the following definitions:
1. 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.
2. Healthcare associated - Blood stream infection present at admission to hospital
or within 48 hours of admission in patients that fulfil ANY of following
criteria:
i. Participant has an intravascular catheter/line that is the source of infection ii.
Attended a hospital or haemodialysis clinic or received intravenous chemotherapy in
the previous 30 days iii. were hospitalized in an acute care hospital for two or more
days in the previous 90 days iv. resided in a nursing home or long-term care facility
v. 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
3. No more than 48 hours has elapsed since the positive blood culture collection.
4. Participant is aged 18 years and over (21 in Singapore)
5. The participant or approved proxy is able to provide informed consent.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
1. Refractory shock or comorbid condition such that patient not expected to survive more
than 7 days.
2. Participant with history of moderate to severe hypersensitivity reaction to a
cephalosporin.
3. Participant with significant polymicrobial bacteraemia including a significant
Gram-positive pathogen (that is, a Gram-positive skin contaminant in one set of blood
cultures is not regarded as significant polymicrobial bacteraemia).
4. Where the bloodstream infection is thought to be related to a vascular catheter and
the catheter is unable to be removed.
5. Treatment is not with the intent to cure the infection (that is, palliative care is an
exclusion).
6. Known pregnancy or breast-feeding.
7. Participant is receiving peritoneal dialysis.
8. Participant previously randomised in this trial.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Randomised controlled trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
28/10/2019
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
29/01/2024
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
513
Query!
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Query!
Recruitment hospital [1]
0
0
Westmead Hospital - Sydney
Query!
Recruitment hospital [2]
0
0
Princess Alexandra Hospital - Brisbane
Query!
Recruitment hospital [3]
0
0
Royal Brisbane and Womens Hospital - Brisbane
Query!
Recruitment hospital [4]
0
0
The Prince Charles Hospital - Brisbane
Query!
Recruitment hospital [5]
0
0
Austin Hospital - Melbourne
Query!
Recruitment postcode(s) [1]
0
0
- Sydney
Query!
Recruitment postcode(s) [2]
0
0
- Brisbane
Query!
Recruitment postcode(s) [3]
0
0
- Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
Malaysia
Query!
State/province [1]
0
0
Kelantan
Query!
Country [2]
0
0
Malaysia
Query!
State/province [2]
0
0
Kuala Lumpur
Query!
Country [3]
0
0
Singapore
Query!
State/province [3]
0
0
Singapore
Query!
Country [4]
0
0
Taiwan
Query!
State/province [4]
0
0
Taichung
Query!
Country [5]
0
0
Taiwan
Query!
State/province [5]
0
0
Tainan
Query!
Country [6]
0
0
Taiwan
Query!
State/province [6]
0
0
Taipei
Query!
Country [7]
0
0
Taiwan
Query!
State/province [7]
0
0
Taoyuan
Query!
Country [8]
0
0
Thailand
Query!
State/province [8]
0
0
Bangkok
Query!
Country [9]
0
0
Thailand
Query!
State/province [9]
0
0
Khon Kaen
Query!
Country [10]
0
0
Turkey
Query!
State/province [10]
0
0
Istanbul
Query!
Funding & Sponsors
Primary sponsor type
Other
Query!
Name
The University of Queensland
Query!
Address
Query!
Country
Query!
Other collaborator category [1]
0
0
Commercial sector/Industry
Query!
Name [1]
0
0
Shionogi
Query!
Address [1]
0
0
Query!
Country [1]
0
0
Query!
Ethics approval
Ethics application status
Query!
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.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT03869437
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
David Paterson, Professor
Query!
Address
0
0
The Univeristy of Queensland
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT03869437
Download to PDF