Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Optimizing Antituberculosis Therapy in Adults With Tuberculous Meningitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03787940
Recruitment Status : Recruiting
First Posted : December 27, 2018
Last Update Posted : July 15, 2019
Sponsor:
Information provided by (Responsible Party):
Beijing Chest Hospital

Brief Summary:
The genetically polymorphic N-acetyltransferase type 2 (NAT2) is responsible for isoniazid metabolism, and rapid acetylators were associated with low concentrations of isoniazid based on previous studies. The investigators hypothesize that among rapid acetylators high dose isoniazid would result in lower rates of death and disability in patients with tuberculous meningitis than the rates with the standard regimen. The investigators recruited patients between the ages of 18 and 65 years with newly diagnosed TBM, then NAT2 genotype will be characterized by using High-Resolution Melting Kit (Zeesan Company, Xiamen). Participants with slow or intermediate acetylators will be administered with standard chemotherapy. For participants with rapid acetylators, patients were stratified at study entry according to the modified British Medical Research Council criteria (MRC grade), then randomly assigned in a 1:1 ratio to receive either standard or with high dose isoniazid treatment. All patients received antituberculosis treatment, which consisted of isoniazid (standard dose or high dose), rifampin, pyrazinamide, ethambutol for 3 months, followed by isoniazid, rifampin and ethambutol at the same doses for an additional 9 months. All patients received adjunctive treatment with dexamethasone for the first 6 to 8 weeks of treatment. 338 participants with rapid acetylators were randomly assigned to group B (standard treatment) and group C (high dose isoniazid), respectively. At the same time, 338 participants with slow or intermediate acetylators were recruited to group A (standard treatment). The primary outcome was death or severe disability 12 months after enrollment. Secondary outcome measures were coma-clearance time, fever-clearance time, and difference of laboratory examination (protein concentration, chloride, glucose and white cell counts) of cerebrospinal fluid.

Condition or disease Intervention/treatment Phase
Tuberculous Meningitis Drug: Isoniazid Not Applicable

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 676 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Optimizing Antituberculosis Therapy in Adults With Tuberculous Meningitis Based on N-Acetyltransferase Type 2 Genotyping
Actual Study Start Date : March 4, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Active Comparator: Standard INH for Non-rapid acetylators
Participant with slow or intermediate acetylators(one of N-Acetyltransferase Type 2 Genotype) administered with standard chemotherapy (3 months HRZE followed by 9 months HRE with standard dose isoniazid)
Drug: Isoniazid
standard dose isoniazid or high dose isoniazid for participants with rapid acetylators

Active Comparator: Standard INH for rapid acetylators
Participant with rapid acetylators(one of N-Acetyltransferase Type 2 Genotype) administered with standard chemotherapy (3 months HRZE followed by 9 months HRE with standard dose isoniazid )
Drug: Isoniazid
standard dose isoniazid or high dose isoniazid for participants with rapid acetylators

Experimental: High dose INH for rapid acetylators
Participant with rapid acetylators(one of N-Acetyltransferase Type 2 Genotype) administered with high dose isonized treatment (3 months HRZE followed by 9 months HRE with high dose isoniazid)
Drug: Isoniazid
standard dose isoniazid or high dose isoniazid for participants with rapid acetylators




Primary Outcome Measures :
  1. Number of Participants with death or severe disability [ Time Frame: up to 12 months after enrollment ]
    Number of Participants with death or severe disability 12 months after enrollment


Secondary Outcome Measures :
  1. days for coma-clearance time [ Time Frame: through study completion,up to 1 year ]
    days for coma-clearance time through study completion

  2. days for fever-clearance time [ Time Frame: through study completion,up to 1 year ]
    days for fever-clearance time through study completion

  3. difference of CSF protein concentration [ Time Frame: 3 months after enrollment ]
    difference of CSF protein concentration (g/L)

  4. difference of CSF glucose concentration [ Time Frame: 3 months after enrollment ]
    difference of CSF glucose concentration (mmol/L)

  5. difference of CSF white cell counts [ Time Frame: 3 months after enrollment ]
    difference of CSF white cell counts (per milliliter)

  6. difference of CSF chloride concentration [ Time Frame: 3 months after enrollment ]
    difference of CSF chloride concentration (mmol/L)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 to 65 years of age;
  • Clinical diagnosis of TBM;
  • Able and willing to provide informed consent to participate in the study.

Exclusion Criteria:

  • Using any other second line antituberculosis drug;
  • Received anti-tuberculosis therapy in the past 3 years;
  • Positive CSF Gram or India ink stain;
  • Received more than 14 days of anti-tuberculosis drugs for the current infection;
  • Known or suspected hypersensitivity to or unacceptable side effects from any oral first line antituberculosis drug;
  • Plasma creatinine concentration was more than the upper limit of the normal range, or the plasma bilirubin concentration was more than 2 times the upper limit of the normal range, or the plasma alanine aminotransferase level was more than three times the upper limit of the normal range;
  • Known or suspected pregnancy;
  • Known or suspected isoniazid and/or rifampin resistant;
  • Lack of consent;
  • Any participant for whom investigators judge this study is not appropriate.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03787940


Contacts
Layout table for location contacts
Contact: Hongfei Duan, MD 13520728402 duanhongfei@hotmail.com
Contact: Lingling Shao, Master 15810187170 shaolinglinglky@163.com

Locations
Layout table for location information
China
Beijing Chest Hospital affiliated to Capital Medical University Recruiting
Beijing, China
Contact: Hongfei Duan         
Jiamusi Infectious Disease Hospital Recruiting
Jiamusi, China
Contact: Chao Qiu         
Jiangxi Provincial Chest Hospital Recruiting
Nanchang, China
Contact: Qilong Zhang         
Zunyi Medical College affiliated Hospital Recruiting
Zunyi, China
Contact: Jianyong Zhang         
Sponsors and Collaborators
Beijing Chest Hospital
Investigators
Layout table for investigator information
Principal Investigator: Hongfei Duan, MD Beijing Chest Hospital

Layout table for additonal information
Responsible Party: Beijing Chest Hospital
ClinicalTrials.gov Identifier: NCT03787940     History of Changes
Other Study ID Numbers: 2018ZX10302302-004
First Posted: December 27, 2018    Key Record Dates
Last Update Posted: July 15, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Beijing Chest Hospital:
N-Acetyltransferase Type 2 Genotype
treatment
Tuberculous Meningitis

Additional relevant MeSH terms:
Layout table for MeSH terms
Tuberculosis
Tuberculosis, Meningeal
Meningitis
Central Nervous System Diseases
Nervous System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Meningitis, Bacterial
Central Nervous System Bacterial Infections
Tuberculosis, Central Nervous System
Central Nervous System Infections
Isoniazid
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents