Therapeutic Drug Monitoring in Patients With Difficult-to-Treat Gram-Negative Bacterial Infections — TDM-RCT  

Sepsis Clinical Trial

Official title: Evaluation of the Efficacy and Safety of Antibiotic Therapeutic Drug Monitoring (TDM) in Patients With Difficult-to-Treat Gram-Negative Bacterial (DT-GNB) Infections

Status Recruiting

Clinical Trial Summary

A prospective, open-label, randomized controlled trial will be conducted to evaluate a novel TDM-guided therapy in management of DT-GNB infections. We hypothesize that TDM-guided antibiotic therapy will reduce 14-day all-cause mortality by 6% (absolute risk reduction) in septic patients with DT-GNB infections, when compared to standard therapy. TDM for 11 antibiotics will be performed for all trial patients although test information will be withheld for the standard therapy arm. The primary aim is to compare the 14-day all-cause mortality rates of novel TDM-guided antibiotic dosing versus standard therapy.

Clinical Trial Description

Sepsis remains a major cause of morbidity and mortality worldwide in the face of antimicrobial resistance especially in patients with Gram-negative bacteria (GNB) infections. Limited new antibiotics for GNB infections pose a severe threat to clinical management of these patients and thus call for old antibiotics to be repurposed. Dosing regimens of old antibiotics often fail to achieve therapeutic drug concentrations in some septic patients. Septic patients commonly have significant hemodynamic changes and/or undergo extracorporeal interventions that may increase patients' susceptibility to treatment failure and increase the chance of more resistant bacteria emergence, or toxicity from the antibiotic. Hence, the "one size fits all" dosing principle for antimicrobial treatments of suspect sepsis due to infection by antibiotic-resistant- or less susceptible-GNB [collectively known as "difficult-to-treat" (DT)-GNB infections] is no longer viable. This will require therapeutic drug monitoring (TDM) to inform if the dosing is adequate to treat such infections.

This study seeks to provide evidence supporting the application of TDM-guided antibiotic therapy on reducing mortality and morbidity among septic patients with DT-GNB infections and significant hemodynamic changes, which can potentially shift current practice paradigms. ;

Related Conditions & MeSH terms

• Antimicrobial Resistance
• Bacterial Infections
• Communicable Diseases
• Hemodynamic Instability
• Infections
• Sepsis
• Therapeutic Drug Monitoring

• NCT number: NCT05942157
• Study type: Interventional
• Source: Singapore General Hospital
• Contact: Tze Peng Lim, PhD
• Phone: +65 6326 6959
• Email: lim.tze.peng@sgh.com.sg
• Status: Recruiting
• Phase: N/A
• Start date: March 29, 2023
• Completion date: December 31, 2025