Monitoring linezolid blood levels to reduce treatment interruptions in rifampin-resistant TB
Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis
This project will test whether checking linezolid blood levels and adjusting doses helps people with rifampin-resistant TB stay on treatment longer.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 280 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Albert Einstein College of Medicine Academic / other |
| Locations | 1 site (East London, Eastern Cape) |
| Trial ID | NCT06590428 on ClinicalTrials.gov |
What this trial studies
This is a pragmatic, open-label, randomized two-arm trial comparing therapeutic drug monitoring (TDM) of linezolid versus standard care in adults treated for rifampin-resistant tuberculosis. Eligible participants must have started a linezolid-containing RR-TB regimen within 14 days and are followed through the roughly six-month course of therapy. The intervention uses trough plasma concentrations to guide dose adjustments aimed at reducing linezolid-associated myelosuppression and peripheral neuropathy that frequently force treatment interruptions. Both HIV-positive and HIV-negative adults are included, and outcomes focus on premature discontinuation of linezolid and safety measures.
Who should consider this trial
Good fit: Adults (>18 years) with microbiologically confirmed rifampin-resistant TB who started a linezolid-containing RR-TB regimen within the previous 14 days and have known HIV status are ideal candidates.
Not a fit: Pregnant people, those initially prescribed less than 600 mg daily of linezolid, patients with severe extrapulmonary TB, or people already well into linezolid therapy are unlikely to gain benefit from participation.
Why it matters
Potential benefit: If successful, TDM could lower linezolid-related toxicity and premature treatment stoppage, improving cure rates and helping prevent the emergence of further drug resistance.
How similar studies have performed: Prior pharmacokinetic and observational work has linked higher linezolid trough levels to toxicity, but randomized evidence that TDM prevents treatment discontinuation is limited, so this approach is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Adult male or female patient \> 18 years of age * Microbiological confirmation of rifampicin-resistant tuberculosis (e.g., phenotypic or genotypic drug susceptibility testing, GeneXpert MTB/RIF™). Participants may have resistance to additional medications as well - i.e., MDR and XDR TB - but must have resistance to at least rifampin * Initiated on a rifampicin-resistant tuberculosis (RR-TB) treatment regimen containing linezolid, no more than 14 days prior to randomization * HIV status is known and confirmed * Both HIV-positive and HIV-negative individuals are eligible * If an individual reports unknown HIV status, they must consent to HIV testing at time of enrollment to confirm status. If they decline to be tested, they are not eligible for the study Exclusion Criteria: * Severe medical condition with expected death in the next 7 days * Pregnant at time of screening * Initial linezolid dose \< 600mg daily * Severe form of extrapulmonary TB (i.e., meningitis, pericarditis, or osteomyelitis) * Unlikely to follow-up at Nkqubela Hospital based on location of residence
Where this trial is running
East London, Eastern Cape
- Nkqubela TB Specialist Hospital — East London, Eastern Cape, South Africa (Recruiting)
Study contacts
- Principal investigator: James CM Brust, MD — Albert Einstein College of Medicine
- Study coordinator: James CM Brust, MD
- Email: james.brust@einsteinmed.edu
- Phone: 718-920-6482
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.