Laura Muñoz1, Miguel Santin1, Fernando Alcaide2, Maria Jesús Ruíz-Serrano3, Paloma Gijón3, Elena Bermúdez3, Angel Domínguez-Castellano4, María Dolores Navarro4, Encarnación Ramírez4, Elvira Pérez-Escolano5, María Dolores López-Prieto5, José Gutiérrez-Rodriguez6, Luis Anibarro7, Laura Calviño7, Matilde Trigo8, Carmen Cifuentes9, Mercedes García-Gasalla9, Antoni Payeras9, Oriol Gasch10, Mateu Espasa11, Ramon Agüero12, Diego Ferrer12, Xavier Casas13, Araceli González-Cuevas14, Alberto García-Zamalloa15, Edurne Bikuña15, María Lecuona16, Rosa Galindo17, Marta Ramírez-Lapausa18, Raquel Carrillo18. 1. Department of Infectious Diseases, Hospital Universitari de Bellvitge-IDIBELL, Barcelona. 2. Department of Microbiology, Hospital Universitari de Bellvitge-IDIBELL, Barcelona. 3. Department of Microbiology and Infectious Diseases, Hospital General Universitario Gregorio Marañón, Madrid. 4. Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Hospital Virgen Macarena, Sevilla. 5. Clinical Unit of Infectious Diseases and Microbiology, Hospital Jerez, Jerez de la Frontera Cádiz. 6. Preventive Medicine, Hospital Puerta del Mar, Cádiz. 7. Infectious Diseases Unit, Complexo Hospitalario de Pontevedra. 8. Department of Microbiology, Complexo Hospitalario de Pontevedra. 9. Department of Internal Medicine, Hospital Son Llàtzer, Palma de Mallorca. 10. Department of Infectious Diseases, Corporació Sanitària Parc Taulí, Sabadell Barcelona. 11. Department of Microbiology, Corporació Sanitària Parc Taulí, Sabadell Barcelona. 12. Respiratory Medicine, Hospital Universitario Marqués de Valdecilla, Santander. 13. Respiratory Medicine Department, Parc Sanitari Sant Joan de Déu, Sant Boi Barcelona. 14. Department of Microbiology, Parc Sanitari Sant Joan de Déu, Sant Boi Barcelona. 15. Department of Internal Medicine, Hospital de Mendaro, Mendaro Gipuzkoa. 16. Department of Microbiology, Hospital Universitario de Canarias, La Laguna Tenerife. 17. Respiratory Medicine, Hospital Universitario de Canarias, La Laguna Tenerife. 18. Department of Internal Medicine, Hospital de Cantoblanco, Madrid, Spain.
Abstract
Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results:A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.
RCT Entities:
Background: Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. Methods: We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. Results: A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). Conclusions: In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. Clinical Trials Registration: NCT01223534.
Authors: Christopher Pease; Alice Zwerling; Ranjeeta Mallick; Mike Patterson; Patricia Demaio; Sandy Finn; Jean Allen; Deborah Van Dyk; Gonzalo G Alvarez Journal: BMC Infect Dis Date: 2019-10-24 Impact factor: 3.090