UnknownNot Applicable

Optimizing Antituberculosis Therapy in Adults With Tuberculous Meningitis

China676 participantsStarted 2019-03-04

Plain-language 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.

Who can participate

Age range18 Years – 65 Years

SexALL

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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.

What they're measuring

Number of Participants with death or severe disability

Timeframe: up to 12 months after enrollment

Trial details

NCT IDNCT03787940

SponsorBeijing Chest Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2021-12-31

Contact for this trial

Hongfei Duan, MD

13520728402 duanhongfei@hotmail.com