Condition or disease | Intervention/treatment | Phase |
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Tuberculosis, Meningeal | Drug: LZD Drug: High dose RIF Drug: Standard dose RIF | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 60 participants |
Allocation: | Randomized |
Intervention Model: | Factorial Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Pharmacokinetics and Tolerability of Adjunctive Linezolid for the Treatment of Tuberculous Meningitis |
Actual Study Start Date : | May 5, 2021 |
Estimated Primary Completion Date : | May 2023 |
Estimated Study Completion Date : | November 2023 |
Arm | Intervention/treatment |
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Experimental: High Dose RIF with LZD
Arm 1 participants will receive high dose oral RIF (35mg/kg/day) and LZD 1200 mg daily for the first 4 weeks of therapy, along with standard doses of Isoniazid (INH), Pyrazinamide (PZA), and Ethambutol (EMB). After 4 weeks, LZD will be discontinued and high dose RIF will return to standard dose for the remainder of treatment.
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Drug: LZD
LZD 1200 mg daily
Other Name: Linezolid
Drug: High dose RIF RIF 35 mg/kg/day
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Experimental: Standard dose RIF with LZD
Arm 2 participants will receive standard dose RIF, INH, PZA, and EMB along with LZD 1200 mg daily. After 4 weeks, LZD will be discontinued.
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Drug: LZD
LZD 1200 mg daily
Other Name: Linezolid
Drug: Standard dose RIF RIF 10 mg/kg/day
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Experimental: High Dose RIF
Arm 3 participants will receive high dose oral RIF (35mg/kg/day) for the first 4 weeks of therapy, along with standard doses of INH, PZA, and EMB. After 4 weeks, high dose RIF will return to standard dose for the remainder of treatment.
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Drug: High dose RIF
RIF 35 mg/kg/day
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Active Comparator: Standard Dose RIF
Arm 4 participants will receive standard doses of RIF, INH, PZA, and EMB.
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Drug: Standard dose RIF
RIF 10 mg/kg/day
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
All participants must have at least one of the following signs/symptoms: headache, irritability, vomiting, fever, neck stiffness, convulsions, focal neurological deficits, altered consciousness, or lethargy. In addition, participants must have CSF glucose to plasma ratio < 0.5 OR positive CSF acid-fast bacilli (AFB) smear OR positive CSF GeneXpert or Xpert Ultra OR clinician intent to initiate TB treatment for suspected TB meningitis.
Definite, probable and possible TBM will be defined as:
Definite TBM is defined by the presence of one or more of the following:
Probable and possible TBM are defined using previously published consensus criteria as shown in Appendix A45.
Exclusion of the most likely alternative diagnoses is also required (e.g., negative cryptococcal antigen). Because culture confirmation is rarely available or often delayed in TBM, patients with probable or possible TBM will be recruited based on these predefined criteria, and CSF will be collected for mycobacterial culture and molecular testing. Classification of participants as definite, probable, or possible TBM will be made retrospectively once all necessary data are available.
Exclusion criteria
Contact: Felicia C Chow, MD | (628) 206 4449 | felicia.chow@ucsf.edu | |
Contact: Victor Arechiga | victor.arechiga@ucsf.edu |
Uganda | |
Masaka Regional Referral Hospital/MRC UVRI Uganda Research Unit on AIDS | Recruiting |
Masaka, Uganda | |
Contact: Freddie Kibengo Freddie.Kibengo@mrcuganda.org |
Principal Investigator: | Felicia C Chow, MD | University of California, San Francisco |
Tracking Information | |||||||||
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First Submitted Date ICMJE | June 3, 2019 | ||||||||
First Posted Date ICMJE | July 16, 2019 | ||||||||
Last Update Posted Date | June 8, 2021 | ||||||||
Actual Study Start Date ICMJE | May 5, 2021 | ||||||||
Estimated Primary Completion Date | May 2023 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Adjunctive Linezolid for the Treatment of Tuberculous Meningitis | ||||||||
Official Title ICMJE | Pharmacokinetics and Tolerability of Adjunctive Linezolid for the Treatment of Tuberculous Meningitis | ||||||||
Brief Summary | This is a phase II randomized open-label trial of high versus standard dose rifampin (RIF) with or without linezolid (LZD) for the first 4 weeks of treatment for Tuberculosis Meningitis (TBM) at Masaka Regional Referral Hospital in Uganda. Initial randomization will be to high (35 mg/kg/day) versus standard (10 mg/kg/day) dose oral rifampin for the first 4 weeks of intensive therapy. Participants will then undergo a second randomization to linezolid 1200 mg daily versus no linezolid for the first 4 weeks of therapy. The primary aims are (1) to determine the cerebrospinal fluid and plasma pharmacokinetics of adjunctive LZD 1200 mg daily in TBM patients receiving high or standard dose RIF and (2) to evaluate the tolerability of a 4-week course of LZD in TBM patients. | ||||||||
Detailed Description | Not Provided | ||||||||
Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Factorial Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Tuberculosis, Meningeal | ||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
60 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | November 2023 | ||||||||
Estimated Primary Completion Date | May 2023 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria
All participants must have at least one of the following signs/symptoms: headache, irritability, vomiting, fever, neck stiffness, convulsions, focal neurological deficits, altered consciousness, or lethargy. In addition, participants must have CSF glucose to plasma ratio < 0.5 OR positive CSF acid-fast bacilli (AFB) smear OR positive CSF GeneXpert or Xpert Ultra OR clinician intent to initiate TB treatment for suspected TB meningitis. Definite, probable and possible TBM will be defined as: Definite TBM is defined by the presence of one or more of the following:
Probable and possible TBM are defined using previously published consensus criteria as shown in Appendix A45.
Exclusion of the most likely alternative diagnoses is also required (e.g., negative cryptococcal antigen). Because culture confirmation is rarely available or often delayed in TBM, patients with probable or possible TBM will be recruited based on these predefined criteria, and CSF will be collected for mycobacterial culture and molecular testing. Classification of participants as definite, probable, or possible TBM will be made retrospectively once all necessary data are available. Exclusion criteria
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
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Listed Location Countries ICMJE | Uganda | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT04021121 | ||||||||
Other Study ID Numbers ICMJE | 18-26068 | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | Felicia Chow, MD, University of California, San Francisco | ||||||||
Study Sponsor ICMJE | University of California, San Francisco | ||||||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | University of California, San Francisco | ||||||||
Verification Date | June 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |