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: To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months. METHODS: This study was a randomized, open-label equivalence trial. HIV-uninfected adults with noncavitary 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 to 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. A total of 370 patients were eligible for per protocol analysis. Thirteen patients in the 4-month arm relapsed, compared with three subjects in the 6-month arm (7.0 vs. 1.6%; risk difference, 0.054; 95% confidence interval with Hauck-Anderson correction, 0.01-0.10). CONCLUSION: Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse.
RCT Entities:
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: To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months. METHODS: This study was a randomized, open-label equivalence trial. HIV-uninfected adults with noncavitary 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 to 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. A total of 370 patients were eligible for per protocol analysis. Thirteen patients in the 4-month arm relapsed, compared with three subjects in the 6-month arm (7.0 vs. 1.6%; risk difference, 0.054; 95% confidence interval with Hauck-Anderson correction, 0.01-0.10). CONCLUSION: Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse.
Authors: Robert S Wallis; T Mark Doherty; Phillip Onyebujoh; Mahnaz Vahedi; Hannu Laang; Ole Olesen; Shreemanta Parida; Alimuddin Zumla Journal: Lancet Infect Dis Date: 2009-03 Impact factor: 25.071
Authors: Gustavo E Velásquez; Meredith B Brooks; Julia M Coit; Henry Pertinez; Dante Vargas Vásquez; Epifanio Sánchez Garavito; Roger I Calderón; Judith Jiménez; Karen Tintaya; Charles A Peloquin; Elna Osso; Dylan B Tierney; Kwonjune J Seung; Leonid Lecca; Geraint R Davies; Carole D Mitnick Journal: Am J Respir Crit Care Med Date: 2018-09-01 Impact factor: 21.405
Authors: Toidi Adekambi; Chris C Ibegbu; Stephanie Cagle; Ameeta S Kalokhe; Yun F Wang; Yijuan Hu; Cheryl L Day; Susan M Ray; Jyothi Rengarajan Journal: J Clin Invest Date: 2015-03-30 Impact factor: 14.808
Authors: Zahoor Ahmad; Eric L Nuermberger; Rokeya Tasneen; Michael L Pinn; Kathy N Williams; Charles A Peloquin; Jacques H Grosset; Petros C Karakousis Journal: J Antimicrob Chemother Date: 2010-01-31 Impact factor: 5.790
Authors: William R Mac Kenzie; Charles M Heilig; Lorna Bozeman; John L Johnson; Grace Muzanye; Denise Dunbar; Kenneth C Jost; Lois Diem; Beverly Metchock; Kathleen Eisenach; Susan Dorman; Stefan Goldberg Journal: PLoS One Date: 2011-04-11 Impact factor: 3.240
Authors: E L Maciel; A P Brioschi; R L Peres; L M Guidoni; F K Ribeiro; D J Hadad; S A Vinhas; E Zandonade; M Palaci; R Dietze; J L Johnson Journal: Int J Tuberc Lung Dis Date: 2013-02 Impact factor: 2.373