Ignite Creation Date:
2025-12-24 @ 1:32 PM
Ignite Modification Date:
2025-12-31 @ 6:13 AM
Study NCT ID:
NCT03537495
Status:
COMPLETED
Last Update Posted:
2023-09-06
First Post:
2018-05-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pharmacokinetic Study of Linezolid for TB Meningitis
Sponsor:
Universitas Padjadjaran
Organization:
Study Overview
Official Title:
Short Intervention and Measurement of Pharmacokinetics of Linezolid in Tuberculosis Meningitis: a Pharmacokinetics and Safety/Tolerability Study
Status:
COMPLETED
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
SIMPLE
Brief Summary:
Tuberculosis meningitis (TBM) is the most severe manifestation of TB, resulting in death or neurological disability in up to 50% of affected patients, despite antibacterial treatment. This TBM treatment follows the model for pulmonary TB by using the same first-line TB drugs (a combination of rifampicin, isoniazid, pyrazinamide and ethambutol) and the same dosing guidelines, although it is known that penetration of two of these drugs (rifampicin and ethambutol) into cerebrospinal fluid (CSF) is limited. Improvement of treatment of TBM is urgently needed.
To do so, a combination of two interventions will be investigated in this study. A series of phase II clinical trials on higher doses of the pivotal TB drug rifampicin in Indonesian patients with TBM have shown that the dose of rifampicin can be increased from 10 mg/kg orally (standard dose) up to 30 mg/kg orally, resulting in a strong increase in exposure to this drug in plasma and CSF, no increase in grade III or IV adverse effects, and a reduction in mortality. Similarly, higher doses of rifampicin up to 35 mg/kg resulted in strong increases in plasma concentrations; the doses were well tolerated and reduced time to sputum conversion in African pulmonary TB patients.
Next to a higher dose of rifampicin, the approved antibacterial drug linezolid seems a good candidate for a new TBM regimen. The drug penetrates well into the CSF and is applied successfully against other central nervous system (CNS) infections (e.g. caused by penicillin-nonsusceptible Streptococcus pneumoniae, vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus). In a study in China, linezolid in a dose of 600 mg BID orally strongly increased recovery of patients with TBM response. Linezolid is also being investigated as a new drug for (drug-resistant) pulmonary TB in numerous studies, in a dose of 1200 mg once daily. More severe adverse effects to this drug typically occur only after prolonged treatment during several months, not during short-term treatment.
Overall, linezolid is expected to be a promising and tolerable candidate for a new intensified TBM treatment regimen consisting of a backbone of high dose rifampicin plus linezolid.
To do so, a combination of two interventions will be investigated in this study. A series of phase II clinical trials on higher doses of the pivotal TB drug rifampicin in Indonesian patients with TBM have shown that the dose of rifampicin can be increased from 10 mg/kg orally (standard dose) up to 30 mg/kg orally, resulting in a strong increase in exposure to this drug in plasma and CSF, no increase in grade III or IV adverse effects, and a reduction in mortality. Similarly, higher doses of rifampicin up to 35 mg/kg resulted in strong increases in plasma concentrations; the doses were well tolerated and reduced time to sputum conversion in African pulmonary TB patients.
Next to a higher dose of rifampicin, the approved antibacterial drug linezolid seems a good candidate for a new TBM regimen. The drug penetrates well into the CSF and is applied successfully against other central nervous system (CNS) infections (e.g. caused by penicillin-nonsusceptible Streptococcus pneumoniae, vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus). In a study in China, linezolid in a dose of 600 mg BID orally strongly increased recovery of patients with TBM response. Linezolid is also being investigated as a new drug for (drug-resistant) pulmonary TB in numerous studies, in a dose of 1200 mg once daily. More severe adverse effects to this drug typically occur only after prolonged treatment during several months, not during short-term treatment.
Overall, linezolid is expected to be a promising and tolerable candidate for a new intensified TBM treatment regimen consisting of a backbone of high dose rifampicin plus linezolid.
Detailed Description:
Overall aim is to determine the most appropriate dose of linezolid in the treatment of TB meningitis, when combined with high-dose rifampicin (35 mg/kg orally), to be tested in larger clinical follow-up studies.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: