Ignite Creation Date:
2024-06-16 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 3:31 PM
Study NCT ID:
NCT06440304
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-06-17
First Post:
2024-05-21
Brief Title:
Therapeutic Options for CRAB
Sponsor:
Clinical Hospital Centre Zagreb
Organization:
Clinical Hospital Centre Zagreb
Study Overview
Official Title:
Therapeutic Strategies for Carbapenem-Resistant Acinetobacter Baumannii Infections Study Protocol
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
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:
TheraCRAB
Brief Summary:
CRAB infections in ICUs are on the rise leading to higher morbidity mortality and healthcare costs due to resistance to most antibiotics including carbapenems The main resistance mechanisms include carbapenemases efflux pumps and changes in the bacterial cell wall
Current treatments include polymyxins Colistin Polymyxin B which are effective but can lead to resistance aminoglycosides Amikacin Gentamicin which are limited by resistance and tetracyclines Tigecycline Eravacycline which are effective against CRAB Fosfomycin is effective in combination treatments and combination therapy eg colistin with sulbactam fosfomycin or eravacycline can enhance outcomes
Previous research shows promise for combination therapies improving treatment efficacy and reducing mortality New regimens are being studied to find optimal combinations Individualized dosing is crucial considering patient-specific factors like age weight and renal function Adjustments depend on the infection site and comorbidities
Strict infection control and antimicrobial stewardship programs ASPs are essential ASPs focus on optimizing antibiotic use and reducing resistance through education and surveillance Future directions include continued research for new drugs or combinations and strategies to overcome resistance and improve treatment efficacy
Study goals include achieving negative samples after 10 days of therapy 30-day survival discharge rates reduced SOFA scores and improved clinical and radiological findings A randomized study will compare colistin combined with fosfomycin ampicillinsulbactam and eravacycline
In summary treating CRAB infections is complex requiring combination therapy individualized dosing and strict infection control measures
Current treatments include polymyxins Colistin Polymyxin B which are effective but can lead to resistance aminoglycosides Amikacin Gentamicin which are limited by resistance and tetracyclines Tigecycline Eravacycline which are effective against CRAB Fosfomycin is effective in combination treatments and combination therapy eg colistin with sulbactam fosfomycin or eravacycline can enhance outcomes
Previous research shows promise for combination therapies improving treatment efficacy and reducing mortality New regimens are being studied to find optimal combinations Individualized dosing is crucial considering patient-specific factors like age weight and renal function Adjustments depend on the infection site and comorbidities
Strict infection control and antimicrobial stewardship programs ASPs are essential ASPs focus on optimizing antibiotic use and reducing resistance through education and surveillance Future directions include continued research for new drugs or combinations and strategies to overcome resistance and improve treatment efficacy
Study goals include achieving negative samples after 10 days of therapy 30-day survival discharge rates reduced SOFA scores and improved clinical and radiological findings A randomized study will compare colistin combined with fosfomycin ampicillinsulbactam and eravacycline
In summary treating CRAB infections is complex requiring combination therapy individualized dosing and strict infection control measures
Detailed Description:
The primary goal will be to negativize positive samples surveillance or diagnostic after 10 days of therapy In addition to the control samples with the same name samples will be taken on the 4th 7th and 10th day after starting treatment
The secondary objectives will include 30-day survival discharge from the ICU discharge from the hospital reduction in SOFA score rate of reinfection and frequency of complications deterioration of renal function Reduction of CRP PCT and leukocytes improvement of the clinical picture improvement of radiological findings such as X-ray of the lungs and reduction of elevated body temperature will also be included
Patients who require treatment in the ICU with a positive sample surveillance or diagnostic for A baumannii with clinical signs of infection temperature 385 CPR 50 L 10000 in which no infection can be explained by another cause will be included
Three groups will be formed
1 colistin fosfomycin
2 colistin ampicilinsulbactam
3 colistin eravacyclin
The outcomes will include a negative sample length of stay in the ICU length of stay in the hospital and reduction of SOFA score
The hypothesis will be that the combination of fosfomycin with colistin and eravacyclin with colistin will lead to faster negative samples than the combination of ampicillinsulbactam with colistin in intensive care unit patients diagnosed with carbapenem-resistant A baumannii
After obtaining approval from the ethics committee of KBC Zagreb this study will be conducted at the UHC Zagreb Department of Anesthesiology and ICU Patients will be randomly divided according to a predetermined randomization table
Upon arrival of a positive microbiological finding on A baumannii the Fosfomycin group will receive fosfomycin 8 g every 8 h together with a colistin bolus of 6 million IJ followed by 3 million IJ every 8 h After the first day the dose will be adjusted according to kidney and liver function Therapy will be administered for 10 days
Upon arrival of a positive microbiological finding on A baumannii the Ampicilinsulbactam group will receive a bolus dose of ampicillinsulbactam 2 g 1 g and a continuous infusion of 8 g 4 g over 24 h together maximum daily dose 12 gday with a colistin bolus of 6 million IJ followed by 3 million IJ every 8 h After the first day the dose will be adjusted according to kidney and liver function Therapy will be performed for 10 days
Upon arrival of a positive microbiological finding for A baumannii the Eravacyclin group will receive eravacycline at a dose of 1 mgkg every 12 h for 60 min together with a colistin bolus of 6 million IU and then 3 million IU every 8 h After the first day the dose will be adjusted according to kidney and liver function Therapy will be administered for 10 days
After the first positive microbiological finding for A baumannii the test will be repeated on the 4th 7th and 10th days from the start of therapy The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study The SOFA score will be calculated daily for each patient over 10 days
Patient data from a hospital information system will be used in this study Demographic data comorbidities habits alcohol and cigarettes Charlson comorbidity index SOFA score allergies and the type of positive sample will be recorded The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study The SOFA score will be calculated daily for each patient over 10 days Patients will be included in the study after the arrival of a microbiological test positive for A baumannii A routine antimicrobial susceptibility test will be performed when the microbiological findings are positive for A baumannii The sensitivity of all A baumannii strains included in the study regardless of the group to which they belonged fosfomycin ampicilinsulbactam and eravacyclin will be determined during the microbiological analysis of all A baumannii strains included in the study After the first positive microbiological finding for A baumannii the test will be repeated on the 3th 7th and 10th days from the start of therapy For each patient included in the study inflammatory parameters leukocytes CRP procalcitonin IL6 and the number of days and discharge from the ICU and hospital as well as 30-day mortality and cause of death complications AKI and ALF and reinfection will be monitored
For a test power of 80 and the use of an independent t-test for the primary objective and a chi-square test for the secondary objective with a statistical significance of 005 it will be necessary to include 108 patients divided into three groups with 36 subjects per group The test for power calculation will be conducted using G Power Version 3196 The results will be processed using IBM SPSS Statistics v27
The secondary objectives will include 30-day survival discharge from the ICU discharge from the hospital reduction in SOFA score rate of reinfection and frequency of complications deterioration of renal function Reduction of CRP PCT and leukocytes improvement of the clinical picture improvement of radiological findings such as X-ray of the lungs and reduction of elevated body temperature will also be included
Patients who require treatment in the ICU with a positive sample surveillance or diagnostic for A baumannii with clinical signs of infection temperature 385 CPR 50 L 10000 in which no infection can be explained by another cause will be included
Three groups will be formed
1 colistin fosfomycin
2 colistin ampicilinsulbactam
3 colistin eravacyclin
The outcomes will include a negative sample length of stay in the ICU length of stay in the hospital and reduction of SOFA score
The hypothesis will be that the combination of fosfomycin with colistin and eravacyclin with colistin will lead to faster negative samples than the combination of ampicillinsulbactam with colistin in intensive care unit patients diagnosed with carbapenem-resistant A baumannii
After obtaining approval from the ethics committee of KBC Zagreb this study will be conducted at the UHC Zagreb Department of Anesthesiology and ICU Patients will be randomly divided according to a predetermined randomization table
Upon arrival of a positive microbiological finding on A baumannii the Fosfomycin group will receive fosfomycin 8 g every 8 h together with a colistin bolus of 6 million IJ followed by 3 million IJ every 8 h After the first day the dose will be adjusted according to kidney and liver function Therapy will be administered for 10 days
Upon arrival of a positive microbiological finding on A baumannii the Ampicilinsulbactam group will receive a bolus dose of ampicillinsulbactam 2 g 1 g and a continuous infusion of 8 g 4 g over 24 h together maximum daily dose 12 gday with a colistin bolus of 6 million IJ followed by 3 million IJ every 8 h After the first day the dose will be adjusted according to kidney and liver function Therapy will be performed for 10 days
Upon arrival of a positive microbiological finding for A baumannii the Eravacyclin group will receive eravacycline at a dose of 1 mgkg every 12 h for 60 min together with a colistin bolus of 6 million IU and then 3 million IU every 8 h After the first day the dose will be adjusted according to kidney and liver function Therapy will be administered for 10 days
After the first positive microbiological finding for A baumannii the test will be repeated on the 4th 7th and 10th days from the start of therapy The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study The SOFA score will be calculated daily for each patient over 10 days
Patient data from a hospital information system will be used in this study Demographic data comorbidities habits alcohol and cigarettes Charlson comorbidity index SOFA score allergies and the type of positive sample will be recorded The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study The SOFA score will be calculated daily for each patient over 10 days Patients will be included in the study after the arrival of a microbiological test positive for A baumannii A routine antimicrobial susceptibility test will be performed when the microbiological findings are positive for A baumannii The sensitivity of all A baumannii strains included in the study regardless of the group to which they belonged fosfomycin ampicilinsulbactam and eravacyclin will be determined during the microbiological analysis of all A baumannii strains included in the study After the first positive microbiological finding for A baumannii the test will be repeated on the 3th 7th and 10th days from the start of therapy For each patient included in the study inflammatory parameters leukocytes CRP procalcitonin IL6 and the number of days and discharge from the ICU and hospital as well as 30-day mortality and cause of death complications AKI and ALF and reinfection will be monitored
For a test power of 80 and the use of an independent t-test for the primary objective and a chi-square test for the secondary objective with a statistical significance of 005 it will be necessary to include 108 patients divided into three groups with 36 subjects per group The test for power calculation will be conducted using G Power Version 3196 The results will be processed using IBM SPSS Statistics v27
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?:
False
Is an FDA AA801 Violation?:
None