Study Results
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Basic Information
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RECRUITING
150 participants
OBSERVATIONAL
2021-06-01
2025-12-31
Brief Summary
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In the present study, data will be collected on antibiotic concentrations in patients treated with beta-lactams for infectious endocarditis as well as patient characteristics and treatment outcomes. A mathematical model will be developed to determine which patient factors determine drug pharmacokinetics. Based on this model, predictions will be made by mathematical simulations on which dosing regimens are optimal for individual patients to ensure therapeutic and non-toxic drug concentrations. In total, 150 patients will be included at four University Hospitals in Sweden; Uppsala University Hospital, Sahlgrenska University Hospital in Gothenburg, Skåne University Hospital in Lund and Karolinska University Hospital in Stockholm. Following informed consent to participate blood samples will be collected at 6 time-points during a dose interval and then at 3 time-points weekly during the full treatment episode (maximum 6 weeks).
Detailed Description
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Inclusion of patients and sample size Patients are prospectively included at the departments of infectious diseases, internal and acute medicine, cardiology and thoracic surgery at four University Hospitals in Sweden; Uppsala University Hospital, Sahlgrenska University Hospital in Gothenburg, Skåne University Hospital in Lund and Karolinska University Hospital in Stockholm. Potential participants are screened for using the electronic medical records. Inclusion criteria are as follows: (1) admission at one of the study wards, (2) a diagnosis of probable or verified infectious endocarditis, (3) treatment with ampicillin, penicillin G, cefotaxime or cloxacillin and (4) informed written consent to participate in the study. The following exclusion criteria will be applied: (1) age less than 18 years and (2) ongoing or planned hemodialysis.
Based on previous research using similar methods, 30 patients per antibiotic substance (total 150 patients) is considered sufficient to develop a robust mathematical model.
Collection of blood samples and patient data Following inclusion, a series of samples will be taken within one week from start of treatment. Beta-lactams are normally prescribed at 6-8 h dose intervals. One series of 6 blood samples will be collected at 0, 0,5, 1, 2, 4 and 6 or 8 h (depending on dose interval, prior to next dose) after administration of antibiotics. Thereafter, samples will be collected once weekly and 0, 3 or 4 (mid-dose interval) and 6 or 8 h (depending on dose interval, prior to next dose).
Information on patient characteristics, including age, body weight, and gender, will be obtained from the electronic medical records. Further, the results of biomarkers (e.g. albumin, creatinine, CRP), collected as part of routine practice, will be noted. If not collected as standard of care, patients will be subject to extra samples to ensure biomarkers are monitored at least twice weekly.
Clinical outcomes Treatment failure is defined as mortality during antibiotic treatment for infectious endocarditis or relapse of endocarditis within 6 months after completion of therapy with isolation of the same pathogens as in the initial episode. Other indicators of treatment failure include acute surgery for endocarditis, clinical deterioration resulting in transfer to the ICU, thromboembolic events more than 7 days after initiation of antibiotics and resistance development of the causative bacteria. The following side effects will be monitored: deterioration of renal impairment, allergic reaction suspected to be caused by the antibiotic treatment, Clostridioides difficile enteritis or other suspected side effects resulting in a shift of therapy to another antibiotic.
Handling of samples and data Blood samples will be stored at -70 degrees Celsius at the Department of infectious diseases at the respective hospital where the samples have been collected. The samples will be sent to Sahlgrenska University Hospital, Gothenburg, for determination of drug concentrations.
Patient names and personal identification numbers will be replaced by a number. Personal data will be stored at the Department of infectious diseases at the respective hospital where the patient has been included. Only the responsible researchers will have access to the code key and be able to link personal information to the individual participants. All information will be handled in accordance with the General Data Protection Regulation (GDPR) and all analyses and presentation of data will be performed using anonymous data.
Mathematical modeling and simulations The collected drug concentrations will be analyzed by non-linear mixed effects modeling using NONMEM. Associations between administered dose and the measured drug concentration over time will be described (pharmacokinetics). Correlations with patient characteristics and biomarkers, as well as clinical outcomes in terms of cure, mortality and documented side effects (pharmacodynamics) will be explored.
Conditions
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Study Design
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CASE_ONLY
PROSPECTIVE
Eligibility Criteria
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Inclusion Criteria
* Intravenous antibiotic therapy with either ampicillin, penicillin G, cefotaxime or cloxacillin
* Signed informed consent to participate in study
Exclusion Criteria
* Ongoing dialysis
18 Years
ALL
No
Sponsors
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Uppsala University
OTHER
Responsible Party
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Principal Investigators
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Thomas Tängdén, MD, Phd
Role: PRINCIPAL_INVESTIGATOR
Uppsala University Hospital
Locations
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Sahlgrenska University Hospital
Gothenburg, , Sweden
Skåne University Hospital
Lund, , Sweden
Karolinska University Hospital
Stockholm, , Sweden
Uppsala University Hospital
Uppsala, , Sweden
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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2019-02886
Identifier Type: -
Identifier Source: org_study_id