Betalactam Pharmacokinetics in Endocarditis Patients

NCT04647331 | Recruiting

• 1 other identifier: 2019-02886
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 4

Brief Summary

Infectious endocarditis (IE) is associated with mortality rates of 10-12%. Adequate antibiotic therapy is crucial for survival and is administered in high doses due to the severity of the disease. In most cases, beta-lactam antibiotics (e.g. ampicillin, penicillin G, cefotaxime or cloxacillin) are employed. A number of patient characteristics, such as age, body weight, and renal function) influence the pharmacokinetics of these drugs. Yet, the interindividual variability is poorly understood meaning that a large proportion of patients are at risk of subtherapeutic or excessive drug concentrations that might result in treatment failure or side effects, respectively. 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).

Conditions

Infective Endocarditis

Keywords

Infective Endocarditis

Outcome Measures

Primary Outcomes (7)

• Determinants of the pharmacokinetic profiles of betalactam antibiotics ampicillin, cefotaxime, cloxacillin and penicillin G

  Data on drug concentrations will be analysed using non-linear mixed effect modeling to describe correlations between the observed concentrations and the administered dose, patient characteristics (e.g., age, body weight, gender) or biomarkers (e.g. albumin, creatinine, CRP)

  6 years

• Maximum drug concentration (Cmax) of betalactam antibiotics ampicillin, cefotaxime, cloxacillin and penicillin G

  Data on drug concentrations will be analysed using non-linear mixed effect modeling to determine Cmax.

  6 years

• Volume of distribution (Vd) of betalactam antibiotics ampicillin, cefotaxime, cloxacillin and penicillin G

  Data on drug concentrations will be analysed using non-linear mixed effect modeling to determine Vd.

  6 years

• Clearance (CL) of betalactam antibiotics ampicillin, cefotaxime, cloxacillin and penicillin G

  Data on drug concentrations will be analysed using non-linear mixed effect modeling to determine CL.

  6 years

• Half-life (t1/2) of betalactam antibiotics ampicillin, cefotaxime, cloxacillin and penicillin G

  Data on drug concentrations will be analysed using non-linear mixed effect modeling to determine t1/2.

  6 years

• Time above the minimum inhibitory concentration (T>MIC) of betalactam antibiotics ampicillin, cefotaxime, cloxacillin and penicillin G

  Data on drug concentrations will be analysed using non-linear mixed effect modeling to determine T\>MIC.

  6 years

• Area under the curve (AUC) of betalactam antibiotics ampicillin, cefotaxime, cloxacillin and penicillin G

  Data on drug concentrations will be analysed using non-linear mixed effect modeling to determine AUC.

  6 years

Secondary Outcomes (8)

• Mortality

  12 months

• Remission of disease

  12 months

• Thromboembolic event

  12 months

• Resistance development

  12 months

• Renal failure

  12 months

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients in Uppsala University Hospital treated for verified or suspected left or right sided endocarditis in nativ or prosthetic valve with intravenous antibiotic therapy (ampicillin, cefotaxime, cloxacillin or penicillin G).

You may qualify if:

• Verified or suspected left or right sided endocarditis in native or prosthetic valve
• Intravenous antibiotic therapy with either ampicillin, penicillin G, cefotaxime or cloxacillin
• Signed informed consent to participate in study

You may not qualify if:

• \<18 years of age
• Ongoing dialysis

Sponsors & Collaborators

• Uppsala University: lead

Study Sites (4)

Sahlgrenska University Hospital

Gothenburg, Sweden

ACTIVE NOT RECRUITING

Skåne University Hospital

Lund, Sweden

RECRUITING

Karolinska University Hospital

Stockholm, Sweden

NOT YET RECRUITING

Uppsala University Hospital

Uppsala, Sweden

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

Endocarditis

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Thomas Tängdén, MD, Phd

  Uppsala University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Tängdén, MD, Phd

CONTACT

+46708370323; thomas.grenholm.tangden@medsci.uu.se

Lisa Faxén, MD

CONTACT

+46768721806; lisa.faxen@medsci.uu.se

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: November 30, 2020
• Study Start: June 1, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (4)