Abstract:

Objective Our aim was to evaluate the clinical efficacy and safety of rifampicin capsule (Ⅱ) (rifampicin capsules embedded by fatty acid matrix) in treatment of pulmonary tuberculosis. Methods In March 2017, Chinese Anti-tuberculosis Association selected 8 designated TB hospitals in 6 provinces from Jiangsu, Shandong, Liaoning, Hunan, Hebei and Shaanxi as the field study implementation units through the method of random number table according to the regions from east, middle or west. From June to December in 2017, each implementing unit enrolled 644 patients in accordance with the inclusion criteria and adopted the continuous inclusion method. Ultimately newly discovered TB patients were assigned into two groups after eliminated invalid data: observated group 330 cases (the rifampicin capsules (Ⅱ) (0.45 g/d, empty stomach, one suit))and the control group 314 cases(the rifampicin capsules (0.6 g/d, empty stomach, one suit)) according to the method of random number table. The two groups all were treated with 2H-R-Z-E/4H-R chemotherapy regimens, all other drugs were the same except rifampicin. During the implementation of the project, if patients fail to complete treatment due to rifampicin resistance or multi-drug resistance or other reasons such as diagnostic changes, they will be included in the withdrawal group. The outcomes of anti-tuberculosis treatment, improvements of tuberculosis-related symptoms, imaging changes of pulmonary lesions, changes of sputum smear, liver and kidney function injury, hemocytopenia and total adverse events in the two groups were observed. SPSS 19.0 software was used for statistical analysis of the data. Chi-square test, Fisher exact probability method or rank sum test were used for enumeration data, and P<0.05 was considered as statistically significant. Results No statistically significant differences between observed group in the outcomes of treatment success (77.6% (256/330)), failure (0.6% (2/330)), loss or death (10.3% (34/330)), withdrawal (11.5% (38/330)) and control group (77.1% (242/314), 0.6% (2/314), 8.9% (28/314), 13.4% (42/314), respectively)(Fisher’s exact probability method, P=0.874). After finishing treatment, in the observed group and the control group, there were no statistically significant differences in cough (91.4%(267/292)and 88.2%(240/272)), fatigue (99.3% (290/292) and 98.2% (267/272)), body mass reduction (100.0% (292/292) and 99.3% (270/272)), fever (100.0% (293/293) and 99.6% (277/278)), the absorption efficiency of TB foci (87.6% (212/242) and 84.1% (196/233)), the cavity improvement rate (57.0% (138/242) and 49.4% (115/233)), and sputum smear positive rate (0.5%(1/210) and 1.0%(2/192)) (χ²=1.590, P=0.207; χ ²=0.732, P=0.392; Fisher’s exact probability method, P=0.234; Fisher’s exact probability method, P=0.487; χ ²=1.189,P=0.276;χ²=2.804,P=0.094; χ²=0.006, P=0.938). The incidence of total adverse events, liver injury and renal function injury in the observed group and the control group (43.3% (143/330) and 44.9% (141/314), 16.7% (55/330) and 18.5% (58/314), 23.6% (78/330) and 24.8% (78/314), respectively)were no statistically significant (χ ²=0.161, 0.362, 0.127, P=0.688, 0.547, 0.721). However, the incidence of reduced blood routine indicators in the control group (26.4% (83/314)) was higher than that in the observed group (17.9% (59/330)) (χ ²=6.850,P=0.009). Conclusion The anti-tuberculosis efficacy and safety of rifampicin capsule (Ⅱ) are not lower than rifampicin capsule, but with a lower dose. This drug provides a new direction for the selection of anti-tuberculosis drugs in China.

Key words: Tuberculosis, pulmonary, Rifampicin capsule (Ⅱ), Drug evaluation, Polypharmacy, Comparative effectiveness research, Data interpretation, statistical