Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06419296
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-17
First Post:
2024-05-14
Brief Title:
Mortality of MBL-producing Enterobacteriaceae Bacteremias With the Combined Use of Ceftazidime-avibactam and Aztreonam vs Other Active Antibiotics A Multicenter Target Trial Emulation
Sponsor:
Hospital Italiano de Buenos Aires
Organization:
Hospital Italiano de Buenos Aires
Study Overview
Official Title:
Mortality of MBL-producing Enterobacteriaceae Bacteremias With the Combined Use of Ceftazidime-avibactam and Aztreonam vs Other Active Antibiotics A Multicenter Target Trial Emulation
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Ceftazidime-avibactam and aztreonam combination CAZAVI ATM presents a potential alternative for the treatment of metallo-beta-lactamase MBL-type carbapenemase-producing Enterobacteriaceae CPE bacteremia particularly where Cefiderocol is not readily available
This study proposes a Target Trial Emulation TTE to assess the efficacy and safety of CAZAVI ATM compared to other active antibiotics OAAs in patients with MBL-type CPE bacteremia and also to evaluate all-cause 30-day mortality resistance profiles of isolated microorganisms clinical failure rates leukocyte count normalization adverse events occurrence of Clostridium difficile infection and emergence of new multidrug-resistant microorganisms
The study expects to enroll at least 662 patients from 22 hospitals in Argentina Data will be collected through the REDCap database with rigorous verification for completeness and accuracy
The outcomes of this project will contribute vital insights into the efficacy and safety of CAZAVI ATM informing clinical practice guidelines for the management of MBL-type bacteremia across diverse settings
This study proposes a Target Trial Emulation TTE to assess the efficacy and safety of CAZAVI ATM compared to other active antibiotics OAAs in patients with MBL-type CPE bacteremia and also to evaluate all-cause 30-day mortality resistance profiles of isolated microorganisms clinical failure rates leukocyte count normalization adverse events occurrence of Clostridium difficile infection and emergence of new multidrug-resistant microorganisms
The study expects to enroll at least 662 patients from 22 hospitals in Argentina Data will be collected through the REDCap database with rigorous verification for completeness and accuracy
The outcomes of this project will contribute vital insights into the efficacy and safety of CAZAVI ATM informing clinical practice guidelines for the management of MBL-type bacteremia across diverse settings
Detailed Description:
Patients will be categorized into two treatment groups for analysis
CAZAVI ATM treatment group and Other Active Antibiotics treatment group As this study is retrospective treatment group assignment will not be a randomized procedure Allocation data will be collected from medical records as a dichotomous variable
In the present study allocation to CAZAVI ATM or OAAs will depend on various factors such as drug availability hospital costs and medical criteria Therefore to ensure comparability among participant characteristics baseline factors will be adjusted to mitigate indication bias
To simulate randomization at baseline identification of MBL-type CPE in blood samples ensuring comparability between treatment groups several covariates will be balanced age sex comorbidities Charlson score Pitt score immunosuppression with neutropenia immunosuppression without neutropenia days of hospitalization prior to culture Sequential Organ Failure Assessment SOFA score days of effective antibiotic treatment between blood culture and positivization 25 Also as this is a multicenter study it will be adjusted for the characteristics of the center public-private including a total of 10 variables to be adjusted for
The start of the follow-up period Time Zero or T0 will be defined by the identification of MBL-type CPE in at least one clinical blood sample blood culture or PCR From this point on all patients will be followed up A 24-hour grace period will be considered from the identification of MBL-type CPE until the patient initiates either of the two treatment groups
To mitigate immortality bias the initiation of both treatment strategies will synchronize with the eligibility criteria at Time Zero of follow-up Thus every patient must remain alive from blood culture collection until MBL detection to be eligible for inclusion in the study and antibiotic treatment must be initiated within 24 hours of detection All enrolled patients will be followed until 30 days after inclusion in the study death or hospital discharge whichever occurs first
A sample calculation was performed to test the null hypothesis of equality in the proportion of deaths among patients who received CAZAVI ATM vs OAAs Falcone et al reported a 19 mortality rate 30 days after inclusion in the CAZAVI ATM arm and a 44 mortality rate in patients with OAAs However for the present study we consider an 80 power is necessary to detect a clinically relevant difference of 15 therefore we expect a mortality of 34 in the OAAs arm and 19 in the CAZAVI ATM arm With an alpha of 5 two-tailed test expected ratio CAZAVI ATMOAAs of 11 a sample size of 270 patients 135 for each branch is calculated
Finally to address indication bias an adjustment will be made with Propensity Score PS matching Considering 10 confounders entered into the model at least 10 to 20 events will be required for each variable Therefore as the outcome of the PS will be the CAZAVI ATM exposure variable at least 150 patients in the CAZAVI ATM branch will be required Thuswe consider the calculation of 300 patients 150 per branch
A meticulous data collection plan will be carried out to ensure accuracy and confidentiality of the information collected The following procedures will be implemented
Data source Data will be obtained from paper or electronic medical records from each participating center Patient tracking will be done through the bacteriology records of each hospital center
Data recording Variables for each patient will be uploaded to a centralized REDCap database The principal investigator and associated investigators of each participating center will be responsible for data upload To maintain privacy and confidentiality each patient will receive a randomly generated registration number to anonymize their identity in the database
Data access Access to center-specific data will be restricted to the principal investigators Researchers will access REDCap using personal credentials limiting data access to authorized personnel only
Confidentiality and anonymization Adherence to legal provisions such as the Argentinian National Personal Data Protection number 25326 and the Habeas Data will be strictly complied with in order to protect the confidentiality and privacy of the patients involved in the study All collected data will be anonymized devoid of patient identifiers
Data storage Once the data upload is completed the entire database will be stored under password and will only be available to the principal investigators of the study All necessary precautions will be taken to ensure that the data are maintained in a secure and reliable environment
The research team is dedicated to upholding data privacy complying with legal regulations and conducting the study ethically and responsibly
CAZAVI ATM treatment group and Other Active Antibiotics treatment group As this study is retrospective treatment group assignment will not be a randomized procedure Allocation data will be collected from medical records as a dichotomous variable
In the present study allocation to CAZAVI ATM or OAAs will depend on various factors such as drug availability hospital costs and medical criteria Therefore to ensure comparability among participant characteristics baseline factors will be adjusted to mitigate indication bias
To simulate randomization at baseline identification of MBL-type CPE in blood samples ensuring comparability between treatment groups several covariates will be balanced age sex comorbidities Charlson score Pitt score immunosuppression with neutropenia immunosuppression without neutropenia days of hospitalization prior to culture Sequential Organ Failure Assessment SOFA score days of effective antibiotic treatment between blood culture and positivization 25 Also as this is a multicenter study it will be adjusted for the characteristics of the center public-private including a total of 10 variables to be adjusted for
The start of the follow-up period Time Zero or T0 will be defined by the identification of MBL-type CPE in at least one clinical blood sample blood culture or PCR From this point on all patients will be followed up A 24-hour grace period will be considered from the identification of MBL-type CPE until the patient initiates either of the two treatment groups
To mitigate immortality bias the initiation of both treatment strategies will synchronize with the eligibility criteria at Time Zero of follow-up Thus every patient must remain alive from blood culture collection until MBL detection to be eligible for inclusion in the study and antibiotic treatment must be initiated within 24 hours of detection All enrolled patients will be followed until 30 days after inclusion in the study death or hospital discharge whichever occurs first
A sample calculation was performed to test the null hypothesis of equality in the proportion of deaths among patients who received CAZAVI ATM vs OAAs Falcone et al reported a 19 mortality rate 30 days after inclusion in the CAZAVI ATM arm and a 44 mortality rate in patients with OAAs However for the present study we consider an 80 power is necessary to detect a clinically relevant difference of 15 therefore we expect a mortality of 34 in the OAAs arm and 19 in the CAZAVI ATM arm With an alpha of 5 two-tailed test expected ratio CAZAVI ATMOAAs of 11 a sample size of 270 patients 135 for each branch is calculated
Finally to address indication bias an adjustment will be made with Propensity Score PS matching Considering 10 confounders entered into the model at least 10 to 20 events will be required for each variable Therefore as the outcome of the PS will be the CAZAVI ATM exposure variable at least 150 patients in the CAZAVI ATM branch will be required Thuswe consider the calculation of 300 patients 150 per branch
A meticulous data collection plan will be carried out to ensure accuracy and confidentiality of the information collected The following procedures will be implemented
Data source Data will be obtained from paper or electronic medical records from each participating center Patient tracking will be done through the bacteriology records of each hospital center
Data recording Variables for each patient will be uploaded to a centralized REDCap database The principal investigator and associated investigators of each participating center will be responsible for data upload To maintain privacy and confidentiality each patient will receive a randomly generated registration number to anonymize their identity in the database
Data access Access to center-specific data will be restricted to the principal investigators Researchers will access REDCap using personal credentials limiting data access to authorized personnel only
Confidentiality and anonymization Adherence to legal provisions such as the Argentinian National Personal Data Protection number 25326 and the Habeas Data will be strictly complied with in order to protect the confidentiality and privacy of the patients involved in the study All collected data will be anonymized devoid of patient identifiers
Data storage Once the data upload is completed the entire database will be stored under password and will only be available to the principal investigators of the study All necessary precautions will be taken to ensure that the data are maintained in a secure and reliable environment
The research team is dedicated to upholding data privacy complying with legal regulations and conducting the study ethically and responsibly
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None