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 urgently needed to boost its coverage and acceptance. Male silicosis patients aged 18 years 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 trails. 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 TB cases. The cumulative active TB rate was 1.67 cases per 100 person-years. Compared to previous study, 1H₃P₃ regimen significantly reduced 3-year cumulative active TB rate than observation group (HR = 0.26, Log-rank <i>P</i> = 0.02), and was comparable with 3HP group (HR = 0.74, Log-rank <i>P</i> = 0.69), while significantly reducing adverse events. 1H₃P₃ TPT regimen was both safe and effective among Chinese silicosis patients. Further work is necessary to test the regimen in other high-risk populations. ClinicalTrials.gov number: NCT03900858. <b>Trial registration:</b>ClinicalTrials.gov identifier: NCT03900858.. <b>Trial registration:</b>ClinicalTrials.gov identifier: NCT06022146..