Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Beta-lactam Pharmacokinetics in Secondary Care

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03033394
Recruitment Status : Completed
First Posted : January 26, 2017
Results First Posted : August 30, 2021
Last Update Posted : August 30, 2021
Sponsor:
Information provided by (Responsible Party):
Imperial College London

Tracking Information
First Submitted Date January 19, 2017
First Posted Date January 26, 2017
Results First Submitted Date August 3, 2020
Results First Posted Date August 30, 2021
Last Update Posted Date August 30, 2021
Actual Study Start Date July 12, 2017
Actual Primary Completion Date August 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: August 4, 2021)
Fraction of the Dosing Interval Over Which the Concentration of Unbound Drug is Greater Than the Minimum Inhibitory Concentration (fT>MIC) [ Time Frame: Two to 10 samples taken during the first 120 hours of antimicrobial therapy ]
Minimum inhibitory concentration (MIC) is the concentration required to visibly inhibit microbial growth in vitro. The MIC for each drug was defined by non-species related breakpoints provided in EUCAST v11.0. Results are given as a fraction of the dosing interval over which the concentration of the unbound drug is greater than the MIC.
Original Primary Outcome Measures
 (submitted: January 24, 2017)
Number of individuals attaining a defined pharmacokinetic-pharmacodynamic target for antimicrobial therapy [ Time Frame: Two to 10 samples taken during the first 120 hours of antimicrobial therapy ]
Time over minimum inhibitory concentration (T>MIC)
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Beta-lactam Pharmacokinetics in Secondary Care
Official Title Defining Adult Beta-lactam Antimicrobial Pharmacokinetics Across the Secondary Care Setting
Brief Summary Currently in the UK, TDM is routinely performed for aminoglycosides and glycopeptide antimicrobial agents, given fears over the narrow therapeutic window of these agents and the serious adverse events associated with toxicity. However, in critical care the role of TDM for optimisation of therapy has been demonstrated to help optimise dosing of patients who tend to have variable pharmacokinetic parameters (J. A. Roberts et al,). This is of growing importance given that low concentrations of antimicrobial agents, below a micro-organisms minimum inhibitory concentration (MIC) is believed to be a major driver of AMR. The investigators set out to explore whether similar observations in PK-PD target variability are currently being observed across the secondary care setting (outside of critical care) and whether these appear to be impacting on clinical outcomes.
Detailed Description

STUDY PARTICIPANTS

  • Participants receiving oral or intravenous therapy will be included in this study.
  • Drug level sampling will be undertaken once the participant is at steady state (after at least 5 doses have been administered to those on treatment).
  • All patients will be consented using the participation information leaflet and consent form provided in appendix 1.

DRUG LEVEL SAMPLING

  • Patients will be identified for inclusion, and researchers will discuss inclusion in the study with the patient and provide clinical information for them to consider. Individuals will be recruited from all areas of secondary care (including, general medicine, general surgery, augmented care, and out-patient parenteral antimicrobial therapy [OPAT]).
  • They will then be consented by researchers after being given at least 24 hours to consider this information and as long as the patient has expressed interest in participating to their treating physician.
  • This will include permission for basic, anonymised demographic and clinical data to be collected related to the patients infection, for which they are receiving antimicrobial therapy.
  • An extra 3mLs of blood will be collected during the patient's routine daily phlebotomy round following their consent. They will be enrolled for up to 72 hours or two days of routine blood tests (whichever is shorter). Up to 10 samples may be taken during the 2 days the patient is enrolled, depending on the number of routine blood tests the patient receives during that day. No more than 3mLs will be taken per each routine blood sample. For example, if the individuals will only have routine blood tests taken at 8am on day 1 and day 2. Then only two extra samples will be taken (3mLs on D1 and 3mLs on D2).
  • The time they received their dose of antimicrobials, the length of infusion time (if available), and time the sample was collected will all be recorded.
  • PK/PD indices for evaluation will be calculated post-hoc during pharmacokinetic-pharmacodynamic analysis. TDM sampling can occur at any time during the dosing schedule (in line with routine blood testing).
  • A standard operating procedure for this study can be found in appendix 3.

SAMPLE PREPARATION AND ANALYSIS

  • All blood samples will be allowed to clot and placed on ice. They will be centrifuged at 2,400rpm for 10 minutes. Sera from each sample will be separated into three vials and stored at -80C.
  • Beta-lactam concentrations will be measured using validated high-performance liquid chromatography methods.
  • Samples will be stored for up to three years post completion of data collection.

    • Consent will be gained for samples to be used for calibration of electrochemical sensors in ex-vivo studies. This will be performed within 90 days of the samples being collected.

PHARMCOKINETIC-PHARMACODYNAMIC MODELLING

  • Data will be anonymised and analysed using Pmetrics in R.
  • Different pharmacokinetic models will be explored using in built statistical analysis options and visual predictive checks.
  • Pharmacodynamic models will then be incorporated into the model using evidence identified in the literature for selection of parameters.
  • Monte Carlo simulation will then be used to for simulation of target attainments and analysis of pharmacodynamic outcomes
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Plasma
Sampling Method Non-Probability Sample
Study Population Participants from a non-critical care setting will be recruited after receiving at least 5 doses of target antimicrobial. Participants receiving oral and intravenous therapy will be eligible.
Condition
  • Pharmacokinetics
  • Beta Lactam Adverse Reaction
  • Penicillin Allergy
Intervention Drug: Beta-lactam antibiotic
Routine clinical dosing
Other Name: Penicillin
Study Groups/Cohorts Beta-lactam antibiotic
Observational pharmacokinetic study of non-critical care patients receiving beta-lactam antibiotics for management of infections.
Intervention: Drug: Beta-lactam antibiotic
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: September 18, 2019)
65
Original Estimated Enrollment
 (submitted: January 24, 2017)
250
Actual Study Completion Date August 1, 2019
Actual Primary Completion Date August 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Adult subjects over 18 years old
  • Capacity to consent to participation
  • Receiving target antimicrobial (amoxicillin, amoxcillin-clavulanate, cefuroxime, ceftriaxone, flucloxacillin, meropenem, piperacillin-tazobactam) for at least 5 doses prior to sampling
  • Appropriate venous access (or for venous access to be gained)

Exclusion Criteria:

  • Children under 18 years old
  • Lacking capacity or prisoner
  • Anaemia or bleeding disorder, deemed significant by the patients physician
  • Patient's physician deems that they are not suitable for inclusion in the study
  • Patients unlikely to be receiving agent for study period
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT03033394
Other Study ID Numbers 207217
16/LO/2179 ( Other Identifier: REC )
33017 ( Other Identifier: NIHR CRN CPMS )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Imperial College London
Study Sponsor Imperial College London
Collaborators Not Provided
Investigators
Principal Investigator: Alison H Holmes, MD MPH MBBS Health Protection Research Unit in HCAI & AMR
PRS Account Imperial College London
Verification Date August 2021