Rifapentine and isoniazid in the continuation phase of a 6-month regimen. Interim report: no activity of isoniazid in the continuation phase.
METHODS
Clinical trial amongst 762 patients with newly diagnosed pulmonary tuberculosis in Hong Kong. After an initial 2 months of a four-drug intensive phase consisting of streptomycin, isoniazid, rifampicin and pyrazinamide (SHRZ), a random allocation in continuation to once-weekly rifapentine + isoniazid (HRp1), HRp1 given in 2 of every 3 weeks (HRp1.2/3), or to three times weekly isoniazid + rifampicin (HR3).


OBJECTIVE
Interim report evaluating progress of study and the role of isoniazid in the continuation phase.


METHODS
Kaplan-Meier analysis and response of patients related to susceptibility of pretreatment organisms to isoniazid and to rate of isoniazid acetylation determined by NAT2 genotyping.


RESULTS
In the 30-month follow-up, rates for adverse treatment events (failure and relapse) were 4.2% in the HR3, 10.2% in the HRp1 and 11.2% in the HRp1.2/3 series (P = 0.02 for HR3 vs HRp1 and P = 0.01 for HR3 vs HRp1.2/3). Occurrence of adverse events was not related to initial susceptibility to isoniazid nor to the rate of acetylation of isoniazid.


CONCLUSIONS
The two rifapentine regimens had similar final rates of adverse 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.
Tam
C M
CM
Wanchai Polyclinic, Kowloon, Hong Kong.
Chan
S L
SL
Kam
K M
KM
Sim
E
E
Staples
D
D
Sole
K M
KM
Al-Ghusein
H
H
Mitchison
D A
DA
D000107:Acetylation; D000995:Antitubercular Agents / Q000627:therapeutic use*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D004359:Drug Therapy, Combination; D005838:Genotype; D006723:Hong Kong; D006801:Humans; D007538:Isoniazid / Q000627:therapeutic use*; D012150:Polymorphism, Restriction Fragment Length; D012293:Rifampin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000235:genetics
D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine