Beta-lactam Therapeutic Drug Monitoring in Singapore

Infection, Bacterial Clinical Trial

— BLAST-2  

Official title:

A Prospective Cohort Study on Beta-lactam Therapeutic Drug Monitoring in Singapore

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04450680
• Other study ID #: BLAST-2
• Status: Recruiting
• Start date: October 10, 2019
• Est. completion date: June 2022

Study information

• Verified date: April 2021
• Source: Singapore General Hospital
• Contact: Nathalie Chua
• Phone: 63213752
• Email: nathalie.grace.sy.chua[@]sgh.com.sg
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Bacterial Infections
• Infection, Bacterial

Intervention

Other:
• Beta-lactam Therapeutic Drug Monitoring
Monitoring serum beta-lactam levels to individualise beta-lactam doses and ensure therapeutic target attainment

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
Singapore General Hospital

Country where clinical trial is conducted

Singapore, 

References & Publications (4)

Heffernan AJ, Sime FB, Lipman J, Roberts JA. Individualising Therapy to Minimize Bacterial Multidrug Resistance. Drugs. 2018 Apr;78(6):621-641. doi: 10.1007/s40265-018-0891-9. Review. — View Citation

Huttner A, Harbarth S, Hope WW, Lipman J, Roberts JA. Therapeutic drug monitoring of the ß-lactam antibiotics: what is the evidence and which patients should we be using it for? J Antimicrob Chemother. 2015 Dec;70(12):3178-83. doi: 10.1093/jac/dkv201. Epub 2015 Jul 17. Review. — View Citation

Roberts JA, Paul SK, Akova M, Bassetti M, De Waele JJ, Dimopoulos G, Kaukonen KM, Koulenti D, Martin C, Montravers P, Rello J, Rhodes A, Starr T, Wallis SC, Lipman J; DALI Study. DALI: defining antibiotic levels in intensive care unit patients: are current ß-lactam antibiotic doses sufficient for critically ill patients? Clin Infect Dis. 2014 Apr;58(8):1072-83. doi: 10.1093/cid/ciu027. Epub 2014 Jan 14. — View Citation

Roberts JA, Ulldemolins M, Roberts MS, McWhinney B, Ungerer J, Paterson DL, Lipman J. Therapeutic drug monitoring of beta-lactams in critically ill patients: proof of concept. Int J Antimicrob Agents. 2010 Oct;36(4):332-9. doi: 10.1016/j.ijantimicag.2010.06.008. Epub 2010 Aug 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	proportion of patients achieving beta-lactam therapeutic targets	proportion of patients achieving beta-lactam therapeutic targets	until end of beta-lactam therapy, an average of 2 weeks