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Rifapentine and isoniazid in the continuation phase of treating pulmonary tuberculosis. Initial report
Abstract:
A randomized comparison has been made of three times weekly rifampin plus isoniazid (HR3) with rifapentine plus isoniazid given once weekly (HRp1) or on 2 of 3 wk (HRp1.2/3) in the continuation phase of 6-mo regimens (each starting with an initial 2 mo of 4-drug therapy) for the treatment of pulmonary tuberculosis in 672 Chinese patients in Hong Kong. Because of poor bioavailability of the rifapentine used (produced in China), its dose size was increased from 600 mg initially to about 750 mg in the last third of patients to obtain serum concentrations similar to those with rifapentine of Western origin; all doses were given after a meal promoting absorption. After initial exclusions, an intent to treat analysis, done on the remaining 592 patients, showed 45 adverse treatment events in 7 of 190 HR3 patients, in 17 of 199 HRp1 patients, and in 21 of 203 HRp1.2/3 patients; of these, 42 were bacteriological or radiographic relapses after the end of treatment (HR3 versus HRp1, p = 0.04; HR3 versus HRp1.2/3, p = 0.01). Patients with organisms initially sensitive or resistant to isoniazid or streptomycin had similar relapse rates. The high relapse rate in the HRp1 regimen suggests that the rifapentine dose should be increased. Similarity of relapse rates, 8.9% and 10.4%, after the HRp1 and HRp1.2/3 regimens, respectively, indicates that irregularity in taking rifapentine/isoniazid could be tolerated. The few adverse side effects in the continuation phase in the rifapentine regimens were less frequent than in the HR3 regimen.
Insights
Weekly rifapentine plus isoniazid regimens showed lower adverse events but higher relapse rates than daily rifampin plus isoniazid for tuberculosis treatment. Increasing rifapentine dosage may be necessary to improve efficacy.
Area of Science:
- Pulmonology
- Infectious Diseases
- Pharmacology
Background:
- Pulmonary tuberculosis treatment typically involves a 6-month regimen.
- The continuation phase is critical for preventing relapse.
- Rifampicin and isoniazid are standard drugs, but alternatives like rifapentine are explored.
Purpose of the Study:
- To compare the efficacy and safety of rifapentine-based regimens versus rifampicin-isoniazid in the continuation phase of tuberculosis treatment.
- To evaluate different dosing frequencies of rifapentine plus isoniazid.
Main Methods:
- A randomized controlled trial involving 672 Chinese patients with pulmonary tuberculosis in Hong Kong.
- Three groups received different continuation phase regimens: rifampicin-isoniazid thrice weekly (HR3), rifapentine-isoniazid once weekly (HRp1), or rifapentine-isoniazid twice weekly (HRp1.2/3).
- An intent-to-treat analysis was performed on 592 patients after exclusions.
Main Results:
- Higher relapse rates were observed in the rifapentine-isoniazid groups (HRp1 and HRp1.2/3) compared to the rifampicin-isoniazid group (HR3).
- Adverse events were less frequent in the rifapentine-based regimens.
- Relapse rates were similar between once-weekly and twice-weekly rifapentine regimens, suggesting some tolerance to irregular dosing.
Conclusions:
- Rifapentine-isoniazid regimens, particularly once-weekly, may require dose optimization to match the efficacy of standard rifampicin-isoniazid therapy.
- Rifapentine-based regimens offer a potential advantage in terms of reduced side effects during the continuation phase.
- Further research is needed to determine optimal rifapentine dosing for tuberculosis treatment.