Trial · NCT04021121
Adjunctive Linezolid for the Treatment of Tuberculous Meningitis
NCT04021121, Phase 2, Completed, University of California, San Francisco; results first posted 2024-10-01
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Adjunctive Linezolid for the Treatment of Tuberculous Meningitis. Trials, record NCT04021121. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04021121
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Adjunctive Linezolid for the Treatment of Tuberculous Meningitis
- NCT number
- NCT04021121
- Status
- Completed
- Phases
- Phase 2
- Enrollment
- 40 participants, actual
- Lead sponsor
- University of California, San Francisco
- Conditions
- Tuberculosis, Meningeal
- Interventions
- LZD, High dose RIF, Standard dose RIF
- First posted
- 2019-07-16
- Last updated
- 2024-10-01
- Results first posted
- 2024-10-01
Source ClinicalTrials.gov
Registered outcomes17
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Drug Clearance (CL/F) | 4 weeks | Parameters were estimated in NONMEM v7.5 using maximum likelihood estimation (MLE) by optimizing the likelihood function based on observed data. The First Order Conditional Estimation (FOCE) method was employed, which linearizes the model around individual-specific estimates to efficiently account for both fixed effects (population-level parameters) and random effects (individual variability). |
| Primary | Volume of Distribution (Vd) | 4 weeks | Parameters were estimated in NONMEM v7.5 using maximum likelihood estimation (MLE) by optimizing the likelihood function based on observed data. The First Order Conditional Estimation (FOCE) method was employed, which linearizes the model around individual-specific estimates to efficiently account for both fixed effects (population-level parameters) and random effects (individual variability). |
| Primary | Plasma Absorption Rate Constant (ka) | 4 weeks | Parameters were estimated in NONMEM v7.5 using maximum likelihood estimation (MLE) by optimizing the likelihood function based on observed data. The First Order Conditional Estimation (FOCE) method was employed, which linearizes the model around individual-specific estimates to efficiently account for both fixed effects (population-level parameters) and random effects (individual variability). |
| Primary | Rate of CSF Uptake (kPC) | 4 weeks | Parameters were estimated in NONMEM v7.5 using maximum likelihood estimation (MLE) by optimizing the likelihood function based on observed data. The First Order Conditional Estimation (FOCE) method was employed, which linearizes the model around individual-specific estimates to efficiently account for both fixed effects (population-level parameters) and random effects (individual variability). |
| Primary | CSF to Plasma Ratio (PC) | 4 weeks | Once plasma parameter estimates were finalized, these were fixed and then linked to CSF concentrations via a hypothetical effect compartment with a unidirectional rate of the entry whose rate was described by KPC and an amount, expressed as PC, or a ratio between plasma concentrations and CSF concentrations. Higher values of KPC indicate faster rates of entry, and higher values of PC indicate greater proportions of linezolid entering from the blood into the CSF. Parameters were estimated in NONMEM v7.5 using maximum likelihood estimation (MLE) by optimizing the likelihood function based on observed data. The First Order Conditional Estimation (FOCE) method was employed, which linearizes the model around individual-specific estimates to efficiently account for both fixed effects (population-level parameters) and random effects (individual variability). |
| Secondary | Proportion of Participants With Grade 3 or Higher Adverse Events (AE). | 4 weeks | |
| Secondary | Proportion of Participants Who Complete LZD Treatment. | 4 weeks | |
| Secondary | Modified Rankin Scale (MRS) Performance. | 4, 12 and 24 weeks | Measures the degree of disability/dependence on a 6 point scale ranging from 0 (no symptoms) to 6 (death). |
| Secondary | Neurocognitive Battery Performance: Wechsler Adult Intelligence Scale-III Digit Symbol (WAIS-III). | 12 and 24 weeks | The WAIS-III assesses speed of information processing. The test consists of 133 small blank squares separated into 7 rows. Each square consists a number ranging from 1-9 and a blank space below. The participant must pair each number in the square with its corresponding symbol provided in a 'key' above the test over a time limit of 90 or 120 seconds. Scores range from 1-133 where higher scores equal indicate better outcomes. |
| Secondary | Neurocognitive Battery Performance: Color Trails, Part 1 | 12 and 24 weeks | The Color Trails, part 1 is used to assess attention and working memory. For this test 25 circles each containing a number between 1 and 25 are randomly placed on a sheet of paper. Participants draw a line between circles as quickly as possible in numerical order. Scores are presented as time to completion. Higher values indicate greater impairment. |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 registered outcomesOutcomes17
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Drug Clearance (CL/F) | 4 weeks | Our primary outcomes include only 2 out of the 4 arms (High dose RIF with LZD + Standard Dose with LZD) because only these 2 arms received linezolid (LZD), and the primary outcomes are measures of LZD pharmacokinetics. Thus, the other 2 arms (High dose RIF with No LZD + Standard Dose with No LZD) are not relevant. Additionally, as pre-specified in the protocol, the 2 arms that received LZD (High dose RIF with LZD + Standard Dose with LZD) are combined. | L/hr | MEAN |
| PRIMARY | Volume of Distribution (Vd) | 4 weeks | Our primary outcomes include only 2 out of the 4 arms (High dose RIF with LZD + Standard Dose with LZD) because only these 2 arms received linezolid (LZD), and the primary outcomes are measures of LZD pharmacokinetics. Thus, the other 2 arms (High dose RIF with No LZD + Standard Dose with No LZD) are not relevant. Additionally, as pre-specified in the protocol, the 2 arms that received LZD (High dose RIF with LZD + Standard Dose with LZD) are combined. | L | MEAN |
| PRIMARY | Plasma Absorption Rate Constant (ka) | 4 weeks | Our primary outcomes include only 2 out of the 4 arms (High dose RIF with LZD + Standard Dose with LZD) because only these 2 arms received linezolid (LZD), and the primary outcomes are measures of LZD pharmacokinetics. Thus, the other 2 arms (High dose RIF with No LZD + Standard Dose with No LZD) are not relevant. Additionally, as pre-specified in the protocol, the 2 arms that received LZD (High dose RIF with LZD + Standard Dose with LZD) are combined. | per hour (hr^-1) | MEAN |
| PRIMARY | Rate of CSF Uptake (kPC) | 4 weeks | Our primary outcomes include only 2 out of the 4 arms (High dose RIF with LZD + Standard Dose with LZD) because only these 2 arms received linezolid (LZD), and the primary outcomes are measures of LZD pharmacokinetics. Thus, the other 2 arms (High dose RIF with No LZD + Standard Dose with No LZD) are not relevant. Additionally, as pre-specified in the protocol, the 2 arms that received LZD (High dose RIF with LZD + Standard Dose with LZD) are combined. | per hour (hr^-1) | MEAN |
| PRIMARY | CSF to Plasma Ratio (PC) | 4 weeks | Our primary outcomes include only 2 out of the 4 arms (High dose RIF with LZD + Standard Dose with LZD) because only these 2 arms received linezolid (LZD), and the primary outcomes are measures of LZD pharmacokinetics. Thus, the other 2 arms (High dose RIF with No LZD + Standard Dose with No LZD) are not relevant. Additionally, as pre-specified in the protocol, the 2 arms that received LZD (High dose RIF with LZD + Standard Dose with LZD) are combined. | ratio | MEAN |
| SECONDARY | Proportion of Participants With Grade 3 or Higher Adverse Events (AE). | 4 weeks | |||
| SECONDARY | Proportion of Participants Who Complete LZD Treatment. | 4 weeks | |||
| SECONDARY | Modified Rankin Scale (MRS) Performance. | 4, 12 and 24 weeks | |||
| SECONDARY | Neurocognitive Battery Performance: Wechsler Adult Intelligence Scale-III Digit Symbol (WAIS-III). | 12 and 24 weeks | |||
| SECONDARY | Neurocognitive Battery Performance: Color Trails, Part 1 | 12 and 24 weeks |
1 to 10 of 17Source ClinicalTrials.gov
See all 17 outcomesResults by group5
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Drug Clearance (CL/F) | Linezolid | 6.24 | 95% Confidence Interval 5.305 to 7.175 | L/hr | |
| Volume of Distribution (Vd) | Linezolid | 24.97 | 95% Confidence Interval 14.024 to 35.976 | L | |
| Plasma Absorption Rate Constant (ka) | Linezolid | 0.35 | 95% Confidence Interval .173 to .527 | per hour (hr^-1) | |
| Rate of CSF Uptake (kPC) | Linezolid | 0.382 | 95% Confidence Interval .278 to .486 | per hour (hr^-1) | |
| CSF to Plasma Ratio (PC) | Linezolid | .5381 | 95% Confidence Interval .46 to .616 | ratio |
Source ClinicalTrials.gov
Participant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | High Dose RIF With LZD | 9 | |
| Overall Study | STARTED | Standard Dose RIF With LZD | 11 | |
| Overall Study | STARTED | High Dose RIF | 10 | |
| Overall Study | STARTED | Standard Dose RIF | 10 | |
| Overall Study | COMPLETED | High Dose RIF With LZD | 6 | |
| Overall Study | COMPLETED | Standard Dose RIF With LZD | 8 | |
| Overall Study | COMPLETED | High Dose RIF | 5 | |
| Overall Study | COMPLETED | Standard Dose RIF | 6 | |
| Overall Study | NOT COMPLETED | High Dose RIF With LZD | 3 | |
| Overall Study | NOT COMPLETED | Standard Dose RIF With LZD | 3 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events96
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Grade 3 or 4 anemia | Blood and lymphatic system disorders | High Dose RIF With LZD | 0 | 9 | 0 |
| other | Grade 3 or 4 anemia | Blood and lymphatic system disorders | Standard Dose RIF With LZD | 1 | 11 | 1 |
| other | Grade 3 or 4 anemia | Blood and lymphatic system disorders | High Dose RIF | 1 | 10 | 1 |
| other | Grade 3 or 4 anemia | Blood and lymphatic system disorders | Standard Dose RIF | 2 | 10 | 2 |
| other | Grade 3 or 4 hyponatremia | Blood and lymphatic system disorders | High Dose RIF With LZD | 0 | 9 | 0 |
| other | Grade 3 or 4 hyponatremia | Blood and lymphatic system disorders | Standard Dose RIF With LZD | 3 | 11 | 3 |
| other | Grade 3 or 4 hyponatremia | Blood and lymphatic system disorders | High Dose RIF | 4 | 10 | 4 |
| other | Grade 3 or 4 hyponatremia | Blood and lymphatic system disorders | Standard Dose RIF | 3 | 10 | 3 |
| other | Grade 3 or 4 elevated total bilirubin | Hepatobiliary disorders | High Dose RIF With LZD | 0 | 9 | 0 |
| other | Grade 3 or 4 elevated total bilirubin | Hepatobiliary disorders | Standard Dose RIF With LZD | 0 | 11 | 0 |
1 to 10 of 96Source ClinicalTrials.gov
See all 96 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | High Dose RIF With LZD | 3 | 9 |
| Total, all-cause mortality | Standard Dose RIF With LZD | 3 | 11 |
| Total, all-cause mortality | High Dose RIF | 5 | 10 |
| Total, all-cause mortality | Standard Dose RIF | 4 | 10 |
| Total, other adverse events | High Dose RIF With LZD | 0 | 9 |
| Total, other adverse events | Standard Dose RIF With LZD | 4 | 11 |
| Total, other adverse events | High Dose RIF | 4 | 10 |
| Total, other adverse events | Standard Dose RIF | 3 | 10 |
| Total, serious adverse events | High Dose RIF With LZD | 5 | 9 |
| Total, serious adverse events | Standard Dose RIF With LZD | 5 | 11 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers0
The papers the trial lists on ClinicalTrials.gov.
None in this release.
Grants1
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
| Project | Title | Principal investigators | Organization | Funder | Fiscal years |
|---|---|---|---|---|---|
| R21TW011035 | Pharmacokinetics and tolerability of adjunctive linezolid for the treatment of tuberculous meningitis | CHOW, FELICIA C. | UNIVERSITY OF CALIFORNIA, SAN FRANCISCO | FOGARTY INTERNATIONAL CENTER | 2018 to 2019 |
Source NIH RePORTER
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests2
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
| Test | Named as | Source |
|---|---|---|
| Category Fluency | Secondary outcome | ConductCognition |
| Verbal Learning | Secondary outcome | ConductCognition |
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT04021121
GET https://conductscience.org/api/trials/v1/NCT04021121/events?page=2