SETTING: An 8-month isoniazid (INH, H) and ethambutol (EMB, E) based regimen recommended by the World Health Organization (WHO) had never been evaluated in a randomised controlled multicentre trial. OBJECTIVE: To compare, in a non-inferiority study design, two 8-month INH+EMB-based regimens with a standard INH and rifampicin (RMP, R) based regimen. DESIGN: A total of 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were randomly allocated to receive 1) daily EMB, INH, RMP and pyrazinamide (PZA, Z) for 2 months, followed by EMB+INH for 6 months (2EHRZ/6HE); 2) the same drugs in the intensive phase but given three times weekly, followed by the same continuation phase of daily EMB+INH (2(EHRZ)(3)/6HE); or 3) a control regimen with the same intensive phase as in regimen 1, followed by 4 months of daily RMP+INH (2EHRZ/4HR). All patients were to be seen and sputum examinations for microscopy and culture carried out at regular intervals up to 30 months after randomisation. RESULTS: At 30 months, failure/relapse rates were 11.7% of 281 2EHRZ/6HE, 15.3% of 301 2(EHRZ)(3)/6HE and 6.0% of 282 2EHRZ/4HR patients (χ(2), 2 degrees of freedom = 12.8, P = 0.002). CONCLUSION: These results confirm earlier findings demonstrating the inferiority of the INH+EMB-based regimens to the standard 6-month regimen. The WHO has withdrawn its recommendation of these regimens.
SETTING: An 8-month isoniazid (INH, H) and ethambutol (EMB, E) based regimen recommended by the World Health Organization (WHO) had never been evaluated in a randomised controlled multicentre trial. OBJECTIVE: To compare, in a non-inferiority study design, two 8-month INH+EMB-based regimens with a standard INH and rifampicin (RMP, R) based regimen. DESIGN: A total of 1355 patients with newly diagnosed smear-positive pulmonary tuberculosis were randomly allocated to receive 1) daily EMB, INH, RMP and pyrazinamide (PZA, Z) for 2 months, followed by EMB+INH for 6 months (2EHRZ/6HE); 2) the same drugs in the intensive phase but given three times weekly, followed by the same continuation phase of daily EMB+INH (2(EHRZ)(3)/6HE); or 3) a control regimen with the same intensive phase as in regimen 1, followed by 4 months of daily RMP+INH (2EHRZ/4HR). All patients were to be seen and sputum examinations for microscopy and culture carried out at regular intervals up to 30 months after randomisation. RESULTS: At 30 months, failure/relapse rates were 11.7% of 281 2EHRZ/6HE, 15.3% of 301 2(EHRZ)(3)/6HE and 6.0% of 282 2EHRZ/4HR patients (χ(2), 2 degrees of freedom = 12.8, P = 0.002). CONCLUSION: These results confirm earlier findings demonstrating the inferiority of the INH+EMB-based regimens to the standard 6-month regimen. The WHO has withdrawn its recommendation of these regimens.
Authors: Yukari C Manabe; Sabine M Hermans; Mohammed Lamorde; Barbara Castelnuovo; C Daniel Mullins; Andreas Kuznik Journal: PLoS One Date: 2012-06-18 Impact factor: 3.240
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Authors: Safaa M Kishk; Kirsty J McLean; Sakshi Sood; Mohamed A Helal; Mohamed S Gomaa; Ismail Salama; Samia M Mostafa; Luiz Pedro S de Carvalho; Andrew W Munro; Claire Simons Journal: Bioorg Med Chem Date: 2019-02-27 Impact factor: 3.641
Authors: Stephen H Gillespie; Angela M Crook; Timothy D McHugh; Carl M Mendel; Sarah K Meredith; Stephen R Murray; Frances Pappas; Patrick P J Phillips; Andrew J Nunn Journal: N Engl J Med Date: 2014-09-07 Impact factor: 91.245