Ethambutol plus isoniazid for the treatment of pulmonary tuberculosis--a controlled trial of our regimens.

A controlled clinical trial of 4 regimens was undertaken in patients with bacteriologically positive, newly-diagnosed pulmonary tuberculosis. The regimens were: ethambutol 15 mg/kg plus isoniazid 400 mg, daily (E7H7); ethambutol 45 mg/kg plus isoniazid 15 mg/kg, twice a week (E2H2); ethambutol 90 mg/kg plus isoniazid 15 mg/kg, once a week plus isoniazid 15 mg/kg, mid-way between the weekly doses (E1H2); and ethambutol 90 mg/kg plus isoniazid 15 mg/kg, once a week (E1H1). All patients received streptomycin 1 g plus ethambutol 25 mg/kg body-weight plus isoniazid 400 mg daily for the first 2 weeks. The total duration of treatment was 12 months for all patients. There were 484 patients admitted to the study. After excluding 60 (41 with initial drug resistance to isoniazid), there remain 424 patients (107 E7H7, 101 E2H2, 107 E1H2, 109 E1H1) in the main analyses. The pretreatment characteristics of the 4 groups were broadly similar. A favourable response at 12 months was observed in 96%, 88%, 93% and 75% of patients respectively: the differences between the E1H1 regimen and the other 3 regimens were all significant (P less than or equal to 0.03) as was that between the E7H7 and E2H2 regimens (P = 0.05). Among the slow inactivators of isoniazid, the proportions with a favourable response at one year were similar in the 4 groups (range 95--91%). However, among the rapid inactivators, the proportion with a favourable response in the E1H1 group was only 57%. There was suggestive evidence that the E1H2 regimen was superior to the E2H2 regimen. Of the patients with bacteriologically quiescent disease at 1 year, approximately a half, at random, had no further chemotherapy and were followed up for a 4-year period. Bacteriological relapse requiring retreatment occurred in 15% of 54 E7H7 patients, 26% of 38 E2H2, 33% of 43 E1H2 and 54% of 37 E1H1 patients, a significant difference (P less than 0.001). A final evaluation of long-term (5-year) favourable response achieved by the 12-month regimens was 83% for the E7H7, 63% for the E2H2, 63% for the E1H2 and 33% for the E1H1 regimens. In general, the regimens were well tolerated and the incidence of adverse reactions to the drugs was low. Of the 424 patients, 6 (1.4%) developed a visual disturbance during the year of chemotherapy.