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High Efficacy of Recombinant Fusion Protein ESAT6-CFP10 as a Skin Test Reagent for Adult Tuberculosis: A Phase III, Multi-Centered, Double-Blind, Hospital-Based, Randomized Controlled Trial
18 Pages Posted: 25 Jul 2022
More...Abstract
The recombinant fusion protein ESAT6-CPF10 (EC) was developed as a novel skin-test reagent to detect Mycobacterium tuberculosis infection. Phase I and phase II trials determined the optimal test parameters of the EC skin-test (ECST) and validated its safety. In the phase III trial, investigators aimed to confirm the diagnostic utility for adult tuberculosis via a multi-centered, double-blind, hospital-based, randomized controlled study. Participants involved in this study included those with active tuberculosis, suspected pulmonary tuberculosis, or non-tuberculosis pulmonary disease. Tuberculin skin test (TST), and ECST were randomly allocated on different arms of each participant after a blood T-SPOT.TB test. The diagnostic accuracy indices of three assays were calculated for a non-inferior comparation, and adverse events were reported. As a result, 1090 adult participants were enrolled in this study. Diagnostic accuracy was analyzed using data from 1085 protocol-compliant participants. The sensitivities of the ECST, TST, and T-SPOT.TB were 91.2% (95%CI, 89.0% - 93.2%), 91.4% (95%CI, 89.1% - 93.3%), and 92.1% (95%CI, 89.9% - 93.9%) respectively. The specificities of the ECST (69.7%, 95%CI, 64.5% - 74.5%) and T-SPOT.TB (76.1%, 95%CI, 71.2% - 80.5%) were significantly higher that of the TST (54.4%, 95%CI, 48.9% - 59.7%). The agreements between ECST and TST (kappa = 0.632) and between ECST and T-SPOT.TB (kappa = 0.780) were substantial. No severe treatment-emergent adverse event was reported (full analysis). In conclusion, the diagnostic performance of the ECST was close to the T-SPOT.TB assay in the detection of adult tuberculosis and indicated good potential for clinical application in common scenarios.
Study Registration: (Registration: CTR20150695).
Funding: The phase III trial was funded by Anhui Longcom Biologic Pharmacy Co. Ltd., China.
This study received grant support from the Shanghai Municipal Health Commission (shslczdzk03002).
Declaration of Interest: None to declare.
Ethical Approval: All study protocols were reviewed and approved by the ethics committee of Shanghai Public Health Clinical Center. All participants signed the informed consent form.
Keywords: Tuberculosis, skin test, ESAT6-CFP10, clinical trial, diagnosis
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