Discontinuation of ethambutol in pulmonary tuberculosis based on results of the MTBDRplus assay

Not Applicable

Completed

Conditions: Certain infectious and parasitic diseases

Registration Number: KCT0000610

Lead Sponsor: Asan Medical Center

Brief Summary: Background We aimed to determine the feasibility of discontinuing ethambutol (EMB) before the end of intensive phase treatment based on the result of GenoType MTBDRplus assay in patients with pulmonary tuberculosis (TB). Methods This prospective, multicenter non-inferiority randomized trial was conducted at 12 referral centers in South Korea in patients with pulmonary TB who received the standard four-drug regimen. In the MTBDRplus group, EMB was discontinued immediately after confirmation that the M. tuberculosis isolate was susceptible to isoniazid and rifampin according to the MTBDRplus assay. In the Guideline group, the timing of EMB discontinuation was determined using results of the phenotypic drug susceptibility test based on the Korean TB guidelines. The primary outcome was treatment success. Secondary outcomes included the 1-year rates of recurrence and adverse events. Results Of the 600 enrolled patients, 507 were randomized, with 419 remaining for primary outcome analysis (MTBDRplus group, 202; Guideline group, 217). Treatment success rates were 94.6% (191/202) and 94.5% (205/217), respectively (P = 0.970), with a relative risk of 1.00 (95% CI 0.95–1.06). For patients followed up for 1 year after treatment, the 1-year recurrence rate did not differ between the two groups (1.1% [2/183] vs. 0.5% [1/199], respectively [P = 0.609]). We found no significant between-group differences of adverse drug reactions. Conclusion Early discontinuation of EMB during the intensive phase based on results of the MTBDRplus assay did not affect treatment outcomes in pulmonary TB.

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 600

Inclusion Criteria

Adult patients (= 18 years of age) (i) with culture-confirmed pulmonary TB or (ii) positive sputum acid-fast bacillus (AFB) smear with imaging findings consistent with pulmonary TB were included.
We included patients who had not yet received treatment for TB or had been under treatment for less than two weeks.

Exclusion Criteria

Exclusion criteria were as follows: (i) history of TB resistant to INH and/or RIF; (ii) inability to receive standard four-drug treatment because of an underlying condition, such as liver or kidney disease; (iii) any condition that may prove fatal during the course of anti-TB treatment, such as advanced-stage cancer; (iv) combined extrapulmonary TB requiring prolonged treatment (e.g., TB meningitis, bone and joint TB); and (v) imaging findings compatible with typical findings of lung disease due to nontuberculous mycobacterium, despite a positive AFB smear in cases for which the AFB culture result was not yet available.