Optimizing Linezolid Dosing in Patients With Advanced Renal Impairment: a Therapeutic Drug Monitoring-based Evaluation
Trial Snapshot
- Phase
- Phase 4
- Status
- Not yet recruiting
- Sponsor
- Alexandria University
- Enrollment
- 50
- Primary Endpoint
- Therapeutic range trough targeting
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Group 1
Linezolid level within therapeutic range
Intervention: Linezolid (IV and PO) (Drug)
Group 2
Above the therapeutic range and within the toxicity range
Intervention: Linezolid (IV and PO) (Drug)
Group 3
Above the therapeutic range and within the toxicity range
Intervention: Linezolid (IV and PO) (Drug)
Outcomes
Primary Outcomes
Therapeutic range trough targeting
Time Frame: From enrollment to the end of antibiotic treatment duration (typically 10 to 14 days)
Linezolid Therapeutic Range Trough Targeting - The proportion of patients whose steady-state linezolid trough concentrations fall within the predefined therapeutic range (e.g., 2-8 mg/L) during treatment as a result of level monitoring and dose correction. This range is the established range for antimicrobial efficacy while minimizing the risk of toxicity, particularly hematological adverse effects. Concentrations will be measured using validated analytical method using HPLC device, and results will be compared to target thresholds to evaluate dosing adequacy.
Secondary Outcomes
- Incidence of New-Onset Thrombocytopenia(From enrollment to the end of antibiotic treatment duration (typically 10 to 14 days))
- Correlation Between Linezolid Trough Concentrations and Thrombocytopenia(From enrollment to the end of antibiotic treatment (typically 10-14 days).)