Ignite Creation Date:
2024-06-16 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06422533
Status:
RECRUITING
Last Update Posted:
2024-06-04
First Post:
2024-04-25
Brief Title:
CeftolozaneTazobactam vs PiperacillinTazobactam for the Treatment of Bacteremia in Hemato-oncological Patients
Sponsor:
Instituto Nacional de Cancerologia de Mexico
Organization:
Instituto Nacional de Cancerologia de Mexico
Study Overview
Official Title:
CeftolozaneTazobactam vs PiperacillinTazobactam for the Treatment of Bacteremia Due to Enterobacteriaceae and Pseudomonas Aeruginosa in Hemato-oncological Patients With Severe Neutropenia and Fever Non-inferiority Study
Status:
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:
None
Brief Summary:
Patients with hematological malignancies receive highly myelotoxic chemotherapy regimens that cause periods of severe myelosuppression which places them at high risk of developing bacteremia
At a global level a very significant increase in multidrug-resistant MDR Gram-negative microorganisms particularly Enterobacteriaceae producing extended-spectrum beta-lactamases ESBL and MDR Paeruginosa have been described during the last decade Among the strategies to reduce bacterial resistance ceftolozanetazobactam CT as a carbapenem-sparing antibiotic has been proposed
CT has broad-spectrum activity since it has action against ESBL-producing Enterobacteriaceae and MDR P aeruginosa Studies carried out in the real world using this antibiotic in patients with hematological malignancies have demonstrated clinical success in reports and case series considered a therapeutic option in patients with Enterobacteriaceae and P aeruginosa infections particularly in MDR pathogens
At the National Cancer Institute in Spanish Instituto Nacional de Cancerologia Gram-negative bacilli have been identified for more than 20 years as the pathogens most frequently associated with bacteremia Escherichia coli occupies the first place in 25 41 ESBL followed by Klebsiella spp in 56 112 ESBL and P aeruginosa in 56 112 MDR The protocol for approaching and treating hematological malignancy patients with severe neutropenia and fever is to initiate an antimicrobial regimen with piperacillintazobactam PT In patients who persist with fever after 48 to 72 hours of starting antibiotics who present with clinical deterioration or in whom PT-resistant bacteria are identified this is escalated to carbapenem
Therefore it is proposed to compare the clinical and microbiological response in patients with hematological malignancies who present with severe neutropenia and fever and who present clinical data of bacteremia with empirical treatment with CT vs PT trying to reduce the use of carbapenems in this group of patients
At a global level a very significant increase in multidrug-resistant MDR Gram-negative microorganisms particularly Enterobacteriaceae producing extended-spectrum beta-lactamases ESBL and MDR Paeruginosa have been described during the last decade Among the strategies to reduce bacterial resistance ceftolozanetazobactam CT as a carbapenem-sparing antibiotic has been proposed
CT has broad-spectrum activity since it has action against ESBL-producing Enterobacteriaceae and MDR P aeruginosa Studies carried out in the real world using this antibiotic in patients with hematological malignancies have demonstrated clinical success in reports and case series considered a therapeutic option in patients with Enterobacteriaceae and P aeruginosa infections particularly in MDR pathogens
At the National Cancer Institute in Spanish Instituto Nacional de Cancerologia Gram-negative bacilli have been identified for more than 20 years as the pathogens most frequently associated with bacteremia Escherichia coli occupies the first place in 25 41 ESBL followed by Klebsiella spp in 56 112 ESBL and P aeruginosa in 56 112 MDR The protocol for approaching and treating hematological malignancy patients with severe neutropenia and fever is to initiate an antimicrobial regimen with piperacillintazobactam PT In patients who persist with fever after 48 to 72 hours of starting antibiotics who present with clinical deterioration or in whom PT-resistant bacteria are identified this is escalated to carbapenem
Therefore it is proposed to compare the clinical and microbiological response in patients with hematological malignancies who present with severe neutropenia and fever and who present clinical data of bacteremia with empirical treatment with CT vs PT trying to reduce the use of carbapenems in this group of patients
Detailed Description:
At a global level a very significant increase in multidrug-resistant MDR Gram-negative microorganisms has been described during the last decade particularly Enterobacteriaceae producing extended-spectrum beta-lactamases ESBL and MDR Pseudomonas aeruginosa This is directly related to the use of broad-spectrum antimicrobials particularly carbapenems Among the strategies to reduce bacterial resistance using ceftolozanetazobactam CT as a carbapenem-sparing antibiotic is proposed CT has been administered in hemato-oncological patients with severe neutropenia colonized by resistant strains in centers with a high prevalence of Enterobacteriaceae-ESBL and P aeruginosa MDR
The studys purpose is to demonstrate non-inferiority between ceftolozanetazobactam vs piperacillintazobactam for patients with hematological malignancies who present severe neutropenia and fever including those patients who have bacteremia due to Enterobacteriaceae and Pseudomonas aeruginosa CT is a combination antibiotic with a new cephalosporin structurally similar to ceftazidime plus tazobactam The FDA approved This known beta-lactamase inhibitor in 2018 to treat intra-abdominal and complicated urinary infections In 2019 its indication was expanded to nosocomial pneumonia and those associated with mechanical ventilation In Mexico it was approved for marketing in June 2019 CT has broad-spectrum activity since it has action against ESBL-producing Enterobacteria and MDR P aeruginosa Studies carried out in the real world using this antibiotic in patients with hematological malignancies have demonstrated clinical success in reports and case series considered a therapeutic option in patients with Enterobacteriaceae and P aeruginosa infections particularly in MDR pathogens
At the National Cancer Institute Gram-negative bacilli have been identified for more than 20 years as the pathogens most frequently associated with bacteremia with Escherichia coli occupying first place at 25 41 ESBL followed by Klebsiella sp in 56 112 ESBL and P aeruginosa in 56 112 MDR The protocol for approaching and treating hemato-oncological patients with severe neutropenia and fever is to initiate an antimicrobial regimen with piperacillintazobactam PT if they are hemodynamically stable In patients who persist with fever after 48 to 72 hours of starting antibiotics who present with clinical deterioration or in whom PT-resistant bacteria are identified this is escalated to a carbapenem usually meropenem
A randomized open non-inferiority clinical trial comparing 11 two antibiotics PT vs CT for the treatment of severe neutropenia and fever andor developing Enterobacteriaceae or P aeruginosa bacteremia in patients with hematologic malignancies
Methodological strategies All patients who come to the National Cancer Institute with signs of severe neutropenia polymorphonuclear cells 500 cellsmm3 and fever 383 degrees Celsius in one measure or 38 degrees Celsius in at least two measures will be considered for inclusion Blood cultures will be taken upon admission catheter and peripheral in those with the same or two peripherals with a difference of 15 minutes between each one Blood cultures will be requested before signing the informed consent since they are part of the initial approach to these patients regardless of whether they enter the study They will be taken before the administration of antimicrobials
Medical staff from the infectious disease department will evaluate the inclusion and exclusion criteria and invite the candidate to the study
If the patient accepts they will be provided informed consent to review it in detail explaining any doubts If they agree to participate the corresponding signatures will be made
Randomization will be done based on a stratified method in two groups Group 1 patients with leukemia and Group 2 patients with other hemato-oncological pathologies They will be randomized into ten blocks and divided into the two groups above
The administration of the PT or CT antimicrobial regimen will begin depending on the group to which they have been assigned following the manufacturers instructions and according to the administration standards at INCan
The clinical and microbiological response will be evaluated in the first 72-96 hours taking randomization as day 1 defined as patient survival plus resolution of fever plus sterilization of blood cultures taken within the first 72-96 hours
If patients have been fever-free for at least 48 hours and have no growth in blood cultures they will receive at least five days of antibiotic treatment
The administration time will be at least seven days in patients with P aeruginosa or Enterobacteriaceae growth in blood cultures
Patients whose blood cultures report growth of bacteria different from the previous ones yeast or polymicrobial growth will be excluded from the study
Treatment failure will be considered and the following will be included in the intention-to-treat analysis
If the growth in the blood culture is Enterobacteriaceae or P aeruginosa resistant to the antibiotic assigned
There is growth of the same bacteria in control blood cultures taken 72-96 hours after starting antibiotics
If during treatment the patient presents signs of hemodynamic instability respiratory failure clinical deterioration or septic shock changing the antimicrobial regimen will be considered
The following will be considered a relapse and will be included in the intention-to-treat analysis
When the same microorganism is isolated at the beginning it grows in blood cultures after having negative blood cultures
Or in the first 30 days after completing the antibiotic regimen considering the resolution of the primary infectious focus
During treatment they will not be able to receive any other Gram-negative antibiotic except prophylaxis against P jirovecii 40080 mgday TMPSMX or 800160 mg every 48 h
The number of days of antibiotics will be counted It will be documented when an antibiotic is modified and the reason for the change microbiological failure clinical deterioration drug-related adverse events and others The appearance of diarrhea will be monitored and Glutamate dehydrogenase GDH and toxin for Clostridiodes difficile will be requested
Patients will be evaluated daily until fever resolution and until hospital discharge if this occurs in the first 14 days recording fever and adverse events including diarrhea leukocytes and neutrophils Follow-up will be carried out until day 30 from the patients inclusion in the study If the patient is discharged before this date a telephone call will be made on day 30 to verify the clinical status
The evolution will be classified as alive without infection alive with clinical or microbiological data of infection also considering C difficile infection dead from infection without neutropenia dead from infection with neutropenia dead from terminal illness or dead from another cause
The studys purpose is to demonstrate non-inferiority between ceftolozanetazobactam vs piperacillintazobactam for patients with hematological malignancies who present severe neutropenia and fever including those patients who have bacteremia due to Enterobacteriaceae and Pseudomonas aeruginosa CT is a combination antibiotic with a new cephalosporin structurally similar to ceftazidime plus tazobactam The FDA approved This known beta-lactamase inhibitor in 2018 to treat intra-abdominal and complicated urinary infections In 2019 its indication was expanded to nosocomial pneumonia and those associated with mechanical ventilation In Mexico it was approved for marketing in June 2019 CT has broad-spectrum activity since it has action against ESBL-producing Enterobacteria and MDR P aeruginosa Studies carried out in the real world using this antibiotic in patients with hematological malignancies have demonstrated clinical success in reports and case series considered a therapeutic option in patients with Enterobacteriaceae and P aeruginosa infections particularly in MDR pathogens
At the National Cancer Institute Gram-negative bacilli have been identified for more than 20 years as the pathogens most frequently associated with bacteremia with Escherichia coli occupying first place at 25 41 ESBL followed by Klebsiella sp in 56 112 ESBL and P aeruginosa in 56 112 MDR The protocol for approaching and treating hemato-oncological patients with severe neutropenia and fever is to initiate an antimicrobial regimen with piperacillintazobactam PT if they are hemodynamically stable In patients who persist with fever after 48 to 72 hours of starting antibiotics who present with clinical deterioration or in whom PT-resistant bacteria are identified this is escalated to a carbapenem usually meropenem
A randomized open non-inferiority clinical trial comparing 11 two antibiotics PT vs CT for the treatment of severe neutropenia and fever andor developing Enterobacteriaceae or P aeruginosa bacteremia in patients with hematologic malignancies
Methodological strategies All patients who come to the National Cancer Institute with signs of severe neutropenia polymorphonuclear cells 500 cellsmm3 and fever 383 degrees Celsius in one measure or 38 degrees Celsius in at least two measures will be considered for inclusion Blood cultures will be taken upon admission catheter and peripheral in those with the same or two peripherals with a difference of 15 minutes between each one Blood cultures will be requested before signing the informed consent since they are part of the initial approach to these patients regardless of whether they enter the study They will be taken before the administration of antimicrobials
Medical staff from the infectious disease department will evaluate the inclusion and exclusion criteria and invite the candidate to the study
If the patient accepts they will be provided informed consent to review it in detail explaining any doubts If they agree to participate the corresponding signatures will be made
Randomization will be done based on a stratified method in two groups Group 1 patients with leukemia and Group 2 patients with other hemato-oncological pathologies They will be randomized into ten blocks and divided into the two groups above
The administration of the PT or CT antimicrobial regimen will begin depending on the group to which they have been assigned following the manufacturers instructions and according to the administration standards at INCan
The clinical and microbiological response will be evaluated in the first 72-96 hours taking randomization as day 1 defined as patient survival plus resolution of fever plus sterilization of blood cultures taken within the first 72-96 hours
If patients have been fever-free for at least 48 hours and have no growth in blood cultures they will receive at least five days of antibiotic treatment
The administration time will be at least seven days in patients with P aeruginosa or Enterobacteriaceae growth in blood cultures
Patients whose blood cultures report growth of bacteria different from the previous ones yeast or polymicrobial growth will be excluded from the study
Treatment failure will be considered and the following will be included in the intention-to-treat analysis
If the growth in the blood culture is Enterobacteriaceae or P aeruginosa resistant to the antibiotic assigned
There is growth of the same bacteria in control blood cultures taken 72-96 hours after starting antibiotics
If during treatment the patient presents signs of hemodynamic instability respiratory failure clinical deterioration or septic shock changing the antimicrobial regimen will be considered
The following will be considered a relapse and will be included in the intention-to-treat analysis
When the same microorganism is isolated at the beginning it grows in blood cultures after having negative blood cultures
Or in the first 30 days after completing the antibiotic regimen considering the resolution of the primary infectious focus
During treatment they will not be able to receive any other Gram-negative antibiotic except prophylaxis against P jirovecii 40080 mgday TMPSMX or 800160 mg every 48 h
The number of days of antibiotics will be counted It will be documented when an antibiotic is modified and the reason for the change microbiological failure clinical deterioration drug-related adverse events and others The appearance of diarrhea will be monitored and Glutamate dehydrogenase GDH and toxin for Clostridiodes difficile will be requested
Patients will be evaluated daily until fever resolution and until hospital discharge if this occurs in the first 14 days recording fever and adverse events including diarrhea leukocytes and neutrophils Follow-up will be carried out until day 30 from the patients inclusion in the study If the patient is discharged before this date a telephone call will be made on day 30 to verify the clinical status
The evolution will be classified as alive without infection alive with clinical or microbiological data of infection also considering C difficile infection dead from infection without neutropenia dead from infection with neutropenia dead from terminal illness or dead from another cause
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