Johnson JL, Jamil Hadad D, Dietze R, Maciel EL, Sewali B, Gitta P, Okwera A, Mugerwa RD, Alcaneses MR, Quelapio MI, Tupasi TE, Horter L, Debanne SM, Eisenach KD, Boom WH
Shortening Treatment in Adults with Non-cavitary Tuberculosis and Two-month Culture Conversion. [JOURNAL ARTICLE]
Am J Respir Crit Care Med 2009 Jun 19.
RATIONALE: Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients.
OBJECTIVES: Assess whether treatment could be shortened from 6 to 4 months in patients with non-cavitary tuberculosis whose sputum cultures converted to negative after 2 months.
METHODS: Randomized, open label equivalence trial. HIV-uninfected adults with non-cavitary tuberculosis were treated daily with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months followed by 2 months of isoniazid and rifampin. After 4 months, patients with drug susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were randomly assigned to continue treatment for 2 more months or stop treatment. Patients were followed for relapse for 30 months after beginning treatment.
MEASUREMENTS AND MAIN RESULTS: Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4 month arm. Three hundred seventy patients were eligible for per protocol analysis. Thirteen patients in the 4 month arm relapsed compared to 3 subjects in the 6 month arm (7.0 % vs. 1.6 %, risk difference 0.054, 95% CI with Hauck-Anderson correction 0.01, 0.10).
CONCLUSION: Shortening treatment from 6 to 4 months in adults with non-cavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of non-cavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse. Clinical Trials Registry Information: ID#NCT00130247 registered at www.clinicaltrials.gov.
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