A CONTROLLED CLINICAL-TRIAL OF ORAL SHORT-COURSE REGIMENS IN THE TREATMENT OF SPUTUM-POSITIVE PULMONARY TUBERCULOSIS

SETTING: The Tuberculosis Research Centre, Chennai, and its unit at Ma durai, South India. OBJECTIVE: To design oral short-course regimens fo r the treatment-of sputum-positive pulmonary tuberculosis that could b e more easily implemented under field conditions. DESIGN: A total of 1 203 patients was randomly allocated to one of three regimens. I (2EHRZ (7)/6EH(7)): 8-month daily regimen of ethambutol (E), isoniazid (H), r ifampicin (R) and pyrazinamide (Z) for 2 months, followed by E and H f or 6 months. II (2EHRZ(2)/4EHR(2)): 6-month twice-weekly regimen with the same four drugs for 2 months, followed by EHR for 4 months. III (2 HRZ(2)/4HR(2)): similar to Reg. II, but without ethambutol. In Reg. I, drugs were given completely unsupervised. Regs. II and III were eithe r 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 bacteriolog ical 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 bacteriolo gical relapse requiring treatment. Giving the twice-weekly regimens pa rtly unsupervised did not influence the response to treatment, emergen ce of drug resistance or relapse rates. Isoniazid resistant group: Unf avourable 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 patien ts) 62% and 15%, respectively. CONCLUSION: A fully unsupervised ethamb utol-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 rifampic in and isoniazid.