Efficacy and safety of a novel short course rifapentine and isoniazid regimen for the preventive treatment of tuberculosis in Chinese silicosis patients: a pilot study (SCRIPT-TB)

Tuberculosis preventive treatment (TPT) is essential for the end TB Strategy, but shorter and better tolerated regimens are needed to boost its coverage and acceptance. Silicosis patients aged 18 to 65 years received a novel 1H3P3 regimen (400 mg isoniazid and 450 mg rifapentine, thrice-weekly for 4 weeks) under direct observation and were actively followed up for 3 years. The safety and efficacy were compared to the 3-month, once-weekly isoniazid/rifapentine (3HP) group and observation group from our previous trials. A total of 279 eligible participants were enrolled, and 238 participants provided informed consent. All eligible participants had a median age of 56 years (IQR 52–60), 163 (68.5%) participants had a Bacillus Calmette-Guerin vaccine scar, and 74 (31.1%) participants were QuantiFERON-TB Gold In-Tube positive. There were 88 adverse events from 66 (27.7%) participants and only one (0.4%) participant had a Grade 3 adverse event. The completion rate was 92.0% (219/238). Six (2.5%) participants were diagnosed with active TB, five of which were bacterial confirmed cases. The cumulative active TB rate was 1.67 cases per 100 person-years. Compared to the previous study, the 1H3P3 regimen significantly reduced the 3-year cumulative active TB rate than the observation group (HR = 0.26, Log-rank <i>P</i> = 0.02) and was comparable with the 3HP group (HR = 0.74, Log-rank <i>P</i> = 0.69), while significantly reducing adverse events. The 1H₃P₃ TPT regimen was both safe and effective among silicosis patients. Further work is necessary to test the regimen in other high-risk populations. <b>Trial registration:</b>ClinicalTrials.gov identifier: NCT06022146 and NCT03900858.