Beta-lactam Therapeutic Drug Monitoring in Singapore

• Conditions: Infection, Bacterial

• Registration Number: NCT04450680
• Lead Sponsor: Singapore General Hospital

Brief Summary

This is a prospective cohort study to evaluate clinical utility and feasibility of beta-lactam therapeutic drug monitoring in Singapore. The investigators hypothesise that conventional beta-lactam dosing regimens based on manufacturer's recommendations (derived from Phase I studies on healthy volunteers) will produce sub-optimal levels in at least half of the patients. Hence, beta-lactam therapeutic drug monitoring and dose individualisation will be required for optimal clinical outcomes. The investigators' secondary aims include correlating various therapeutic targets with clinical outcomes to identify a suitable therapeutic target for clinical use and to characterise beta-lactam pharmacokinetics in sub-group of patients with complex pharmacokinetics so that local empirical dosing regimens can be formulated.

Detailed Description

Despite widespread use, conventional beta-lactam dosing regimens, derived from healthy volunteers, are sub-optimal clinically as patients display variable pharmacokinetics. This problem is further confounded by rising antimicrobial resistance and the need for high dose beta-lactams, exceeding licensed recommendations. In order to optimise beta-lactam therapy, dose individualisation using therapeutic drug monitoring (TDM) has been suggested. However, experience with beta-lactam TDM is limited with varying practices worldwide. Therapeutic targets are also variable and have not been extensively validated. Hence, this study primarily aims to establish clinical feasibility and utility of beta-lactam TDM. The investigators hypothesise that conventional beta-lactam dosing will produce sub-optimal levels in at least half of the patients, justifying need for TDM and dose individualisation to improve clinical outcomes. The secondary aims include correlating various therapeutic targets with clinical outcomes to identify a suitable therapeutic target for clinical use and to characterise beta-lactam pharmacokinetics and recommend local empirical dosing regimens.

The investigators propose a prospective cohort study on adult patients (≥21 years) admitted to SGH. Four blood samples will be obtained over a dosing interval and assayed using liquid chromatography with tandem mass spectrometry. Levels and dose adjustment recommendations will be reported to physicians by infectious disease pharmacists.

Study Timeline

• Study Start: 2019-10-10
• Study First Submitted: 2020-06-12
• Study First Submitted QC: 2020-06-26
• Study First Posted: 2020-06-29
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-09
• Last Update Posted: 2021-04-14
• Primary Completion: 2021-12
• Study Completion: 2022-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Adult patients (21 years and above)
• Admitted to Singapore General Hospital
• Receiving beta-lactam therapy for documented or suspected infection
• Indication for beta-lactam therapeutic drug monitoring: critically ill, altered pharmacokinetics (burns, obese, on extracorporeal therapy, dialysis), immunocompromised, resistant pathogens, deep-seated infections, suspected or at risk for adverse effects

Exclusion Criteria

• Expected mortality within next 24 hours
• Pregnancy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
proportion of patients achieving beta-lactam therapeutic targets	until end of beta-lactam therapy, an average of 2 weeks	proportion of patients achieving beta-lactam therapeutic targets

Trial Locations

Locations (1)

Singapore General Hospital; 🇸🇬 Singapore, Singapore