Rifapentine and isoniazid in the continuation phase of a 6-month regimen. Interim report: no activity of isoniazid in the continuation phase

SETTING: Clinical trial amongst 762 patients with newly diagnosed pulmonary tuberculosis in Hong Kong. After an initial 2 months of a four-drug intens ive phase consisting of streptomycin, isoniazid, rifampicin and pyrazinamid e (SHRZ), a random allocation in continuation to once-weekly rifapentine isoniazid (HRp(1)), HRp(1) given in 2 of every 3 weeks (HRp(1).2/3), or to three times weekly isoniazid + rifampicin (HR3). OBJECTIVE: Interim report evaluating progress of study and the role of ison iazid in the continuation phase. METHODS: Kaplan-Meier analysis and response of patients related to suscepti bility of pretreatment organisms to isoniazid and to rate of isoniazid acet ylation determined by NAT2 genotyping. RESULTS: In the 30-month follow-up, rates for adverse treatment events (fai lure and relapse) were 4.2% in the HR3, 10.2% in the HRp(1) and 11.2% in th e HRp1.2/3 series (P = 0.02 for HR3 vs HRp(1) and P = 0.01 for HR3 vs HRp1. 2/3). Occurrence of adverse events was not related to initial susceptibilit y to isoniazid nor to the rate of acetylation of isoniazid. CONCLUSIONS: The two rifapentine regimens had similar final rates of advers e events which were unsatisfactory. Isoniazid had little or no activity in the continuation phase, indicating that no improvement of the continuation regimen is likely to be obtained by alteration of the isoniazid dosage.