Controlled trial of intermittent regimens of rifampicin plus isoniazid for pulmonary tuberculosis in Singapore

Abstract

A total of 481 adult Chinese, Malays, and Indians in Singapore with newly diagnosed smear-positive pulmonary tuberculosis were allocated at random to four regimens of intermittent rifampicin plus isoniazid. All patients received an initial 2 weeks of daily streptomycin plus isoniazid plus rifampicin. This was followed either by twice-weekly isoniazid 15 mg/kg plus rifampicin 900 mg (HR2 regimen) or 600 mg (LR2 regimen), or by once-weekly isoniazid 15 mg/kg plus rifampicin 900 mg (HR1 regimen) or 600 mg (LR1 regimen). In addition, all patients received a daily capsule containing, at random, either rifampicin 25 mg or a matched placebo to see if the rifampicin supplement would reduce the incidence of adverse reactions to the drug. At 12 months, all the patients on the two twice-weekly regimens (HR2, LR2) had a favourable bacteriological status as had 97% of 102 HR1 and 93% of 112 LR1 patients. The therapeutic response was significantly better on the twice-weekly than on the once-weekly regimens (P = 0-0005), but the dose size of rifampicin did not have a statistically significant effect. Adverse reactions to intermittent rifampicin occurred in 25% of the HR1 patients but on the other three regimens their incidence was low. The incidence of rifampicin-dependent antibodies was higher, ranging from 48% (HR1) to 24% (LR2). The effect of dose size on the incidence of the "flu" syndrome (the commonest reaction) and of antibodies was statistically significant (P less than 0-01 and less than 0-001, respectively). The interval between doses affected the incidence of the "flu" syndrome (P less than 0-001), but not of antibodies (P greater than 0-25). The rifampicin 25 mg supplement had no effect therapeutically or on the incidence of adverse reactions or of antibodies.