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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/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
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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)
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Secondary ID [1]
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GAME CHANGER
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Universal Trial Number (UTN)
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Trial acronym
GAMECHANGER
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Bloodstream Infections
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Condition category
Condition code
Infection
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Studies of infection and infectious agents
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Infection
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Other infectious diseases
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Inflammatory and Immune System
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Other inflammatory or immune system disorders
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Mortality at 14 days
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Assessment method [1]
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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.
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Timepoint [1]
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14 days post date of randomisation
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Secondary outcome [1]
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Mortality post blood stream infection of each regimen at longer time points
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Assessment method [1]
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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.
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Timepoint [1]
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30 and 90 days, from day of randomisation or "day 1"
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Secondary outcome [2]
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Clinical and microbiological failure at day 14
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Assessment method [2]
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Defined as composite of:
1. Death
2. Still in hospital and clinical failure, as de?ned by
1. If baseline SOFA =3, D(day)14 SOFA not improved by =30%
2. If baseline SOFA \<3, D14 SOFA worse
3. 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)
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Timepoint [2]
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Day 14, from day of randomisation or "day 1"
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Secondary outcome [3]
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Microbiological failure days 3 to 90 post randomisation
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Assessment method [3]
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De?ned as growth in blood cultures of the same GNB as the index blood culture(s), from day 3 up to day 90.
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Timepoint [3]
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Day 3 through to day 90
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Secondary outcome [4]
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Colonisation or infection with methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Gram-negative bacilli or Candida bloodstream infection.
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Assessment method [4]
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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.
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Timepoint [4]
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Day 3 through to day 90
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Secondary outcome [5]
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Clostridioides di?cile infection days 3 to 90 post randomisation.
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Assessment method [5]
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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).
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Timepoint [5]
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Day 3 through to day 90
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Secondary outcome [6]
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Improvement in functional status at day 30 post randomisation compared to baseline.
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Assessment method [6]
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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) \[McNamara et al. Clin Microbiol Infect. 2020 Feb;26(2):257.e1-257\].
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Timepoint [6]
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Day 30, from day of randomisation or "day 1"
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Secondary outcome [7]
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Time to hospital discharge.
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Assessment method [7]
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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.
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Timepoint [7]
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From day of randomisation or "day 1" through to day 90
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Secondary outcome [8]
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Treatment emergent SAEs (Serious Adverse Events)
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Assessment method [8]
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Defined as a serious adverse event possibly, probably or definitely related to the randomised drug treatment.
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Timepoint [8]
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From day of randomisation or "day 1" through to 5 days post end of study treatment.
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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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
28/10/2019
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
29/01/2024
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Sample size
Target
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Accrual to date
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Final
513
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
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Recruitment hospital [1]
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Westmead Hospital - Sydney
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Recruitment hospital [2]
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Princess Alexandra Hospital - Brisbane
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Recruitment hospital [3]
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Royal Brisbane and Womens Hospital - Brisbane
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Recruitment hospital [4]
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The Prince Charles Hospital - Brisbane
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Recruitment hospital [5]
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Austin Hospital - Melbourne
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Recruitment postcode(s) [1]
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- Sydney
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Recruitment postcode(s) [2]
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- Brisbane
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Recruitment postcode(s) [3]
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- Melbourne
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Recruitment outside Australia
Country [1]
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Malaysia
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State/province [1]
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Kelantan
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Country [2]
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Malaysia
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State/province [2]
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Kuala Lumpur
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Country [3]
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Singapore
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State/province [3]
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Singapore
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Country [4]
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Taiwan
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State/province [4]
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Taichung
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Country [5]
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Taiwan
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State/province [5]
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Tainan
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Country [6]
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Taiwan
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State/province [6]
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Taipei
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Country [7]
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Taiwan
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State/province [7]
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Taoyuan
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Country [8]
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Thailand
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State/province [8]
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Bangkok
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Country [9]
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Thailand
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State/province [9]
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Khon Kaen
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Country [10]
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Turkey
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State/province [10]
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Istanbul
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Funding & Sponsors
Primary sponsor type
Other
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Name
The University of Queensland
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Address
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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Shionogi
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/study/NCT03869437
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Trial related presentations / publications
Wright H, Harris PNA, Chatfield MD, Lye D, Henderson A, Harris-Brown T, Donaldson A, Paterson DL. Investigator-Driven Randomised Controlled Trial of Cefiderocol versus Standard Therapy for Healthcare-Associated and Hospital-Acquired Gram-negative Bloodstream Infection: Study protocol (the GAME CHANGER trial): study protocol for an open-label, randomised controlled trial. Trials. 2021 Dec 7;22(1):889. doi: 10.1186/s13063-021-05870-w.
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Public notes
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Contacts
Principal investigator
Name
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David Paterson, Professor
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Address
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The Univeristy of Queensland
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Type
Other Details
Attachment
Statistical analysis plan
https://cdn.clinicaltrials.gov/large-docs/37/NCT03869437/SAP_000.pdf
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT03869437
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