Beta-lactam Therapeutic Drug Monitoring in Singapore

NCT ID: NCT04450680

Last Updated: 2021-04-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

80 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-10-10

Study Completion Date

2022-06-30

Brief Summary

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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

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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.

Conditions

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Infection, Bacterial

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Beta-lactam Therapeutic Drug Monitoring

Monitoring serum beta-lactam levels to individualise beta-lactam doses and ensure therapeutic target attainment

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

21 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Singapore General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nathalie Chua

Role: PRINCIPAL_INVESTIGATOR

Singapore General Hospital

Locations

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Singapore General Hospital

Singapore, , Singapore

Site Status RECRUITING

Countries

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Singapore

Central Contacts

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Nathalie Chua

Role: CONTACT

Andrea Kwa

Role: CONTACT

Facility Contacts

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Nathalie Chua

Role: primary

References

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Huttner A, Harbarth S, Hope WW, Lipman J, Roberts JA. Therapeutic drug monitoring of the beta-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.

Reference Type BACKGROUND
PMID: 26188037 (View on PubMed)

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 beta-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.

Reference Type BACKGROUND
PMID: 24429437 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20685085 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29569104 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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BLAST-2

Identifier Type: -

Identifier Source: org_study_id

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