Optimizing Antituberculosis Therapy in Adults With Tuberculous Meningitis
Status:
Recruiting
Trial end date:
2021-12-31
Target enrollment:
Participant gender:
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.