<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04450680</url>
  </required_header>
  <id_info>
    <org_study_id>BLAST-2</org_study_id>
    <nct_id>NCT04450680</nct_id>
  </id_info>
  <brief_title>Beta-lactam Therapeutic Drug Monitoring in Singapore</brief_title>
  <acronym>BLAST-2</acronym>
  <official_title>A Prospective Cohort Study on Beta-lactam Therapeutic Drug Monitoring in Singapore</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Singapore General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Singapore General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective cohort study to evaluate clinical utility and feasibility of&#xD;
      beta-lactam therapeutic drug monitoring in Singapore. The investigators hypothesise that&#xD;
      conventional beta-lactam dosing regimens based on manufacturer's recommendations (derived&#xD;
      from Phase I studies on healthy volunteers) will produce sub-optimal levels in at least half&#xD;
      of the patients. Hence, beta-lactam therapeutic drug monitoring and dose individualisation&#xD;
      will be required for optimal clinical outcomes. The investigators' secondary aims include&#xD;
      correlating various therapeutic targets with clinical outcomes to identify a suitable&#xD;
      therapeutic target for clinical use and to characterise beta-lactam pharmacokinetics in&#xD;
      sub-group of patients with complex pharmacokinetics so that local empirical dosing regimens&#xD;
      can be formulated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite widespread use, conventional beta-lactam dosing regimens, derived from healthy&#xD;
      volunteers, are sub-optimal clinically as patients display variable pharmacokinetics. This&#xD;
      problem is further confounded by rising antimicrobial resistance and the need for high dose&#xD;
      beta-lactams, exceeding licensed recommendations. In order to optimise beta-lactam therapy,&#xD;
      dose individualisation using therapeutic drug monitoring (TDM) has been suggested. However,&#xD;
      experience with beta-lactam TDM is limited with varying practices worldwide. Therapeutic&#xD;
      targets are also variable and have not been extensively validated. Hence, this study&#xD;
      primarily aims to establish clinical feasibility and utility of beta-lactam TDM. The&#xD;
      investigators hypothesise that conventional beta-lactam dosing will produce sub-optimal&#xD;
      levels in at least half of the patients, justifying need for TDM and dose individualisation&#xD;
      to improve clinical outcomes. The secondary aims include correlating various therapeutic&#xD;
      targets with clinical outcomes to identify a suitable therapeutic target for clinical use and&#xD;
      to characterise beta-lactam pharmacokinetics and recommend local empirical dosing regimens.&#xD;
&#xD;
      The investigators propose a prospective cohort study on adult patients (≥21 years) admitted&#xD;
      to SGH. Four blood samples will be obtained over a dosing interval and assayed using liquid&#xD;
      chromatography with tandem mass spectrometry. Levels and dose adjustment recommendations will&#xD;
      be reported to physicians by infectious disease pharmacists.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 10, 2019</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>proportion of patients achieving beta-lactam therapeutic targets</measure>
    <time_frame>until end of beta-lactam therapy, an average of 2 weeks</time_frame>
    <description>proportion of patients achieving beta-lactam therapeutic targets</description>
  </primary_outcome>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Infection, Bacterial</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Beta-lactam Therapeutic Drug Monitoring</intervention_name>
    <description>Monitoring serum beta-lactam levels to individualise beta-lactam doses and ensure therapeutic target attainment</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients admitted to the above-mentioned hospital and receiving beta-lactam therapy&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients (21 years and above)&#xD;
&#xD;
          -  Admitted to Singapore General Hospital&#xD;
&#xD;
          -  Receiving beta-lactam therapy for documented or suspected infection&#xD;
&#xD;
          -  Indication for beta-lactam therapeutic drug monitoring: critically ill, altered&#xD;
             pharmacokinetics (burns, obese, on extracorporeal therapy, dialysis),&#xD;
             immunocompromised, resistant pathogens, deep-seated infections, suspected or at risk&#xD;
             for adverse effects&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Expected mortality within next 24 hours&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nathalie Chua</last_name>
    <role>Principal Investigator</role>
    <affiliation>Singapore General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Nathalie Chua</last_name>
    <phone>63213752</phone>
    <email>nathalie.grace.sy.chua@sgh.com.sg</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Andrea Kwa</last_name>
    <phone>63266959</phone>
    <email>andrea.kwa.l.h@sgh.com.sg</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Singapore General Hospital</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nathalie Chua</last_name>
      <phone>63213752</phone>
      <email>nathalie.grace.sy.chua@sgh.com.sg</email>
    </contact>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>26188037</PMID>
  </reference>
  <reference>
    <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 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.</citation>
    <PMID>24429437</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20685085</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>29569104</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 29, 2020</study_first_posted>
  <last_update_submitted>April 9, 2021</last_update_submitted>
  <last_update_submitted_qc>April 9, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bacterial Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lactams</mesh_term>
    <mesh_term>beta-Lactams</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 11, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/80/NCT04450680/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04450680
org study id: BLAST-2
nct id: NCT04450680
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Cohort
time perspective: Prospective
measure: proportion of patients achieving beta-lactam therapeutic targets
time frame: until end of beta-lactam therapy, an average of 2 weeks
description: proportion of patients achieving beta-lactam therapeutic targets
intervention type: Other
intervention name: Beta-lactam Therapeutic Drug Monitoring
description: Monitoring serum beta-lactam levels to individualise beta-lactam doses and ensure therapeutic target attainment
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 99 Years
healthy volunteers: No
last name: Nathalie Chua
role: Principal Investigator
affiliation: Singapore General Hospital
last name: Nathalie Chua
phone: 63213752
email: nathalie.grace.sy.chua@sgh.com.sg
last name: Andrea Kwa
phone: 63266959
email: andrea.kwa.l.h@sgh.com.sg
facility: 
status: Recruiting
contact: 
country: Singapore
citation: 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.
PMID: 26188037
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 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.
PMID: 24429437
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.
PMID: 20685085
citation: 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.
PMID: 29569104
responsible party type: Sponsor
mesh term: Bacterial Infections
mesh term: Lactams
mesh term: beta-Lactams
sharing ipd: No
provided document: 