Optimizing Linezolid Dosing in Patients With Advanced Renal Impairment: a Therapeutic Drug Monitoring-based Evaluation
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Linezolid (IV and PO), Linezolid (IV and PO), Linezolid (IV and PO).
- Who it may be relevant to
- Registry conditions: Kidney Disease. Basic parameters: 18 years — 90 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Center list to be confirmed — check the primary protocol.
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
The goal of this clinical trial is to adjust the Linezolid dose according to its blood level in adults with kidney diseases. It will also learn about the safety of linezolid. The main questions it aims to answer are: * How often does linezolid require level monitoring? * How often does linezolid require dose adjustment? * What medical benefits do participants have when linezolid level monitoring is applied? Researchers will compare two dose reduction regimens when they have evidence of overexposure to determine which regimen is more effective in preventing thrombocytopenia (Platelet drop). Participants will: * Withdrew linezolid level every 2 to 4 days of the antibiotic course. * Visit the clinic twice for checkups and tests.
Detailed description
Linezolid is a crucial antibiotic prescribed for the treatment of various infectious diseases such as pneumonia, skin infections, and catheter-related bloodstream infections. Linezolid covers gram-positive bacteria, including Methicillin-resistant Staphylococcus Auris (MRSA) and Vancomycin-resistant Staphylococcus Auris (VRSA).
Recently, Linezolid usage has become favorable for chronic kidney disease (CKD) patients to preserve the remaining residual renal function by avoiding nephrotoxic antibiotics such as vancomycin and aminoglycosides. However, linezolid-induced thrombocytopenia hinders linezolid use in the CKD population due to accumulation and overexposure. Recent literature suggested implementing a therapeutic drug monitoring (TDM) approach to modify the dose regimen and minimize linezolid toxicity.
The obstacle faced was the lack of clear TDM-based linezolid modification guidelines for CKD patients. To overcome this issue, we conducted a pilot study involving 15 patients (7 ESRD, 5 CKD, and 3 AKI on top of CKD). Patients with evidence of toxic levels (8 patients) underwent dose adjustment from 600mg every 12 hours to 300mg every 12 hours.
Dose reduction by 50% with no change in dose interval resulted in a decrease in supratherapeutic trough levels. However, these levels, while lower, did not consistently reach the predefined target therapeutic range (2-8 mg/dl).
The recent approach we are investigating now is to both lower the dose and elongate the interval.
The aim of the work is to optimize renal dosing adjustment with patients having linezolid by investigating whether once-daily dosing administration of linezolid provides better trough-range targeting over twice-daily targeting.
Research Steps
1. Patients were interviewed and selected according to the study's selection criteria. 2. Blood tests were taken before the start of the study to assess their condition and record their medical history before starting linezolid treatment. 3. Participants were divided into three groups based on linezolid drug concentrations compared to the pre-defined target therapeutic range, as determined by the pharmacotherapy monitoring guidelines:
I. Group 1: Within the therapeutic range: No intervention and continued linezolid 600 mg every 12 hours.
II. Group 2: Above the therapeutic range and within the toxicity range: Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 300 mg every 12 hours.
III. Group 3: Above the therapeutic range and within the toxicity range: Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 600 mg every 24 hours. 4. Patient follow-up was conducted at the end of the study and comparisons were made between the different groups.
Interventions
- Drug Linezolid (IV and PO)
No dose change and continued linezolid 600 mg every 12 hours. - Drug Linezolid (IV and PO)
Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 300 mg every 12 hours. - Drug Linezolid (IV and PO)
Intervention and adjustment of the linezolid dose from 600 mg every 12 hours to 600 mg every 24 hours.
Primary outcome measures
- Therapeutic range trough targeting [Time frame: From enrollment to the end of antibiotic treatment duration (typically 10 to 14 days)]
Secondary outcome measures (2)
- Incidence of New-Onset Thrombocytopenia [Time frame: From enrollment to the end of antibiotic treatment duration (typically 10 to 14 days)]
- Correlation Between Linezolid Trough Concentrations and Thrombocytopenia [Time frame: From enrollment to the end of antibiotic treatment (typically 10-14 days).]
Eligibility criteria
Inclusion criteria
- Advanced renal impairment, Hemodialysis patients
Exclusion criteria
- Pregnancy, Lactating females, Advanced Liver impairment, Cases using antidepressants or antipsychotics, Cases suffering from Hematological blood diseases, and/or chronic Immune thrombocytopenia.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Center list to be confirmed — check the primary protocol.
Identifiers
NCT: NCT07138521 · Linezolid TDM