SETTING: The Tuberculosis Research Centre, Chennai, and its unit at Madurai, South India. OBJECTIVE: To design oral short-course regimens for the treatment of sputum-positive pulmonary tuberculosis that could be more easily implemented under field conditions. DESIGN: A total of 1203 patients was randomly allocated to one of three regimens. I (2EHRZ7/6EH7): 8-month daily regimen of ethambutol (E), isoniazid (H), rifampicin (R) and pyrazinamide (Z) for 2 months, followed by E and H for 6 months. II (2EHRZ2/4EHR2): 6-month twice-weekly regimen with the same four drugs for 2 months, followed by EHR for 4 months. III (2HRZ2/4HR2): similar to Reg. II, but without ethambutol. In Reg. I, drugs were given completely unsupervised. Regs. II and III were either completely or partially supervised. RESULTS: Drug-susceptible group: At the end of treatment, 3.6% of 305 patients in Reg. I, 0.4% of 263 in Reg. II and 9.3% of 257 in Reg. III had an unfavourable bacteriological response. By 24 months after start of treatment, 5% of 290 in Reg. I, 11% of 258 in Reg. II and 10% of 229 in Reg. III had a bacteriological relapse requiring treatment. Giving the twice-weekly regimens partly unsupervised did not influence the response to treatment, emergence of drug resistance or relapse rates. Isoniazid resistantgroup: Unfavourable response and relapse with Reg. I (94 patients) was 17% and 8%, with Reg. II (59 patients) 20% and 25%, and with Reg. III (74 patients) 62% and 15%, respectively. CONCLUSION: A fully unsupervised ethambutol-containing regimen given daily for 8 months (Reg. I) was found to be very effective even in the presence of isoniazid-resistant bacilli. With the ethambutol-containing twice-weekly regimen, the response at the end of treatment was near 100%, but the relapse rate was high (11%). The non-ethambutol twice-weekly regimen was not satisfactory. All three regimens failed in the presence of bacilli resistant to rifampicin and isoniazid.
RCT Entities:
SETTING: The Tuberculosis Research Centre, Chennai, and its unit at Madurai, South India. OBJECTIVE: To design oral short-course regimens for the treatment of sputum-positive pulmonary tuberculosis that could be more easily implemented under field conditions. DESIGN: A total of 1203 patients was randomly allocated to one of three regimens. I (2EHRZ7/6EH7): 8-month daily regimen of ethambutol (E), isoniazid (H), rifampicin (R) and pyrazinamide (Z) for 2 months, followed by E and H for 6 months. II (2EHRZ2/4EHR2): 6-month twice-weekly regimen with the same four drugs for 2 months, followed by EHR for 4 months. III (2HRZ2/4HR2): similar to Reg. II, but without ethambutol. In Reg. I, drugs were given completely unsupervised. Regs. II and III were either completely or partially supervised. RESULTS: Drug-susceptible group: At the end of treatment, 3.6% of 305 patients in Reg. I, 0.4% of 263 in Reg. II and 9.3% of 257 in Reg. III had an unfavourable bacteriological response. By 24 months after start of treatment, 5% of 290 in Reg. I, 11% of 258 in Reg. II and 10% of 229 in Reg. III had a bacteriological relapse requiring treatment. Giving the twice-weekly regimens partly unsupervised did not influence the response to treatment, emergence of drug resistance or relapse rates. Isoniazid resistant group: Unfavourable response and relapse with Reg. I (94 patients) was 17% and 8%, with Reg. II (59 patients) 20% and 25%, and with Reg. III (74 patients) 62% and 15%, respectively. CONCLUSION: A fully unsupervised ethambutol-containing regimen given daily for 8 months (Reg. I) was found to be very effective even in the presence of isoniazid-resistant bacilli. With the ethambutol-containing twice-weekly regimen, the response at the end of treatment was near 100%, but the relapse rate was high (11%). The non-ethambutol twice-weekly regimen was not satisfactory. All three regimens failed in the presence of bacilli resistant to rifampicin and isoniazid.
Authors: Federica Fregonese; Shama D Ahuja; Onno W Akkerman; Denise Arakaki-Sanchez; Irene Ayakaka; Parvaneh Baghaei; Didi Bang; Mayara Bastos; Andrea Benedetti; Maryline Bonnet; Adithya Cattamanchi; Peter Cegielski; Jung-Yien Chien; Helen Cox; Martin Dedicoat; Connie Erkens; Patricio Escalante; Dennis Falzon; Anthony J Garcia-Prats; Medea Gegia; Stephen H Gillespie; Judith R Glynn; Stefan Goldberg; David Griffith; Karen R Jacobson; James C Johnston; Edward C Jones-López; Awal Khan; Won-Jung Koh; Afranio Kritski; Zhi Yi Lan; Jae Ho Lee; Pei Zhi Li; Ethel L Maciel; Rafael Mello Galliez; Corinne S C Merle; Melinda Munang; Gopalan Narendran; Viet Nhung Nguyen; Andrew Nunn; Akihiro Ohkado; Jong Sun Park; Patrick P J Phillips; Chinnaiyan Ponnuraja; Randall Reves; Kamila Romanowski; Kwonjune Seung; H Simon Schaaf; Alena Skrahina; Dick van Soolingen; Payam Tabarsi; Anete Trajman; Lisa Trieu; Velayutham V Banurekha; Piret Viiklepp; Jann-Yuan Wang; Takashi Yoshiyama; Dick Menzies Journal: Lancet Respir Med Date: 2018-04 Impact factor: 102.642
Authors: Dick Menzies; Andrea Benedetti; Anita Paydar; Sarah Royce; Pai Madhukar; William Burman; Andrew Vernon; Christian Lienhardt Journal: PLoS Med Date: 2009-09 Impact factor: 11.069
Authors: H R Stagg; R J Harris; H-A Hatherell; D Obach; H Zhao; N Tsuchiya; K Kranzer; V Nikolayevskyy; J Kim; M C Lipman; I Abubakar Journal: Thorax Date: 2016-06-13 Impact factor: 9.139