Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06651047
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-10-15
Brief Title:
PKPD Analysis of CeftazidimeAvibactam or Cefiderocol With or Without Fosfomycin for the Treatment of Difficult To-treat Gram-negative Infections
Sponsor:
None
Organization:
None
Study Overview
Official Title:
PharmacokineticPharmacodynamic Analysis of CeftazidimeAvibactam or Cefiderocol With or Without Fosfomycin for the Treatment of Difficult To-treat Gram-negative Infections
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PACCOF
Brief Summary:
A multicenter national prospective observational pharmacological study of patients with difficult-to-treat Gram-negative infections treated with ceftazidimeavibactam CAZAVI or cefiderocol CEF monotherapy or combination therapy with ceftazidimeavibactam associated with fosfomycin FOS or cefiderocol associated with fosfomycin
Detailed Description:
Gram-negative infections particularly those caused by Carbapenem-resistant Enterobacterales CRE have a dramatic impact on patient survival Despite the introduction of new drugs in the last years have improved the outcome of patients with difficult-to-treat gram-negative infections mortality and relapse rates are still relevant especially in patients with high-risk sources such as pneumonia and those in which the attainment of optimal exposure could be reduced by underlying renal disease The use of a combination regimen in these scenarios has been proposed However a standardized approach to therapeutic management is still missing To overcome this unmet clinical need this study aims to investigate the pharmacokineticpharmacodynamics PKPD optimization of antibiotic dosing regimens in patients with difficult-to-treat Gram-negative infections using Therapeutic Drug Monitoring TDM A prompt implementation of an appropriate targeted antibiotic therapy could represent a valuable approach to improve clinical outcomes in patients with difficult-to-treat Gram-negative infections Moreover more information is needed in pediatric populations where ceftazidimeavibactam CAZAVI is approved only for children aged 3 months with the same indications as adults and cefiderocol CEF is not approved Indeed cefiderocol is currently off-label administered in pediatric population using case-by-case dosages based on encouraging case reports
Since several in vitro studies have highlighted the synergistic effect of fosfomycin FOS with different antibiotic classes including cephalosporins such drug could be an appealing option in combination therapy for the management of difficult-to-treat gram-negative infections both with CAZAVI and CEF However real-life prospective studies are needed to investigate the potential benefit of combination therapy on clinical outcomes and the occurrence of further resistance Thus the correct dose of FOS along with the type of administration ie intermittent extended or continuous infusion are issues to establish
In particular the primary aim of the study is to evaluate the probability of achieving pre-determined pharmacokineticpharmacodynamic PKPD efficacy targets for CAZAVI CEF and FOS
Secondary objectives are
to evaluate the relationship between the achievement of the PKPD target of CAZAVI CEF and FOS and microbiological eradication
to evaluate the trend of clinical biomarkers in response to antibiotic therapy
to investigate the diagnostic and prognostic value of protein biomarkers
This research is supported by EU funding within the Next Generation EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases Project no PE00000007 INF-ACT
Since several in vitro studies have highlighted the synergistic effect of fosfomycin FOS with different antibiotic classes including cephalosporins such drug could be an appealing option in combination therapy for the management of difficult-to-treat gram-negative infections both with CAZAVI and CEF However real-life prospective studies are needed to investigate the potential benefit of combination therapy on clinical outcomes and the occurrence of further resistance Thus the correct dose of FOS along with the type of administration ie intermittent extended or continuous infusion are issues to establish
In particular the primary aim of the study is to evaluate the probability of achieving pre-determined pharmacokineticpharmacodynamic PKPD efficacy targets for CAZAVI CEF and FOS
Secondary objectives are
to evaluate the relationship between the achievement of the PKPD target of CAZAVI CEF and FOS and microbiological eradication
to evaluate the trend of clinical biomarkers in response to antibiotic therapy
to investigate the diagnostic and prognostic value of protein biomarkers
This research is supported by EU funding within the Next Generation EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases Project no PE00000007 INF-ACT
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None