Montejano R, de la Calle-Prieto F, Velasco M, Guijarro C, Queiruga-Parada J, Jiménez-González M, González-Ruano P, Martínez P, Goikoetxea AJ, Ibarrola M, Ciudad M, Gutiérrez Á, Torralba M, Díaz-Brasero A, Ryan P, Marcelo C, Díez C, Ibarra S, Merino E, Estrada V, Marcos J, Novella M, Rivera MA, Ruiz-Muñoz M, de Miguel M, Soler L, Del Álamo M, Moreno S, Carcas AJ, Borobia AM, and Arribas JR
Background: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation., Methods: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected., Results: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib., Conclusions: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials., Clinical Trials Registration: EudraCT: 2020-001156-18., Competing Interests: Potential conflicts of interest. P. R. has received grant support and honoraria from Gilead and MSD; consulting fees from AbbVie SL; payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from ViiV and Gilead Sciences; and support for attending meetings and/or travel from AbbVie and GSK (ViiV). J. V. has received scholarships and honorarium as speaker for Gilead Sciences. M. S. has received honoraria from Gilead; has developed educational material for MSD and ViiV Healthcare; and has served on advisory boards for MSD and Gilead. A. M. B. reports grants or contracts from GSK, Moderna, and Janssen (paid to institution); advisory fees from Janssen and Pfizer (paid to author); participation on a data and safety monitoring board (DSMB) for Pfizer, Janssen, and Medical Developments International (paid to author); payment or honoraria for lectures, presentations, manuscript writing, or educational events from Gilead and Pfizer (paid to author); and speaker’s fees from Janssen (paid to author). J. R. A. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Merck (paid to author); support for attending meetings and/or travel from MSD (paid to author); and consulting fees, advisory fees, and speaker’s fees from Gilead, Merck, Pfizer, Sobi, GSK, MSD, Serono, Lilly, and Roche (paid to author); he is also a member of the Infectious Diseases and Clinical Microbiology Society COVID-19 treatment guidelines. A. G. L. reports payment or honoraria for presentation from Gilead Sciences, and support for attending meetings and/or travel from Angelini Pharma España. A. J. C. reports grants or contracts from ISCIII, Ministry of Innovation and Science of Spain (PI21/01507, PI18/00136, CM19/00243, ICI21/00065), and Vaccelerate (Clinical trial name: EU-Covat-1 Aged); payment or honoraria for a course on clinical investigation (paid to institution) from AbbVie, and participation on a DSMB or advisory board for AMR Insights (paid to institution). C. G. reports consulting fees, participation on a DSMB or advisory board, and payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Amgen, Daiichi Sankyo, Ferrer, and Sanofi; and support for attending meetings and/or travel from Sanofi and Ferrer. L. S. reports grants or contracts from Novartis and Boehringer, and support for attending meetings and/or travel from Novartis. M. R.-M. reports support for attending meetings and/or travel from Roche Farma SA. M. N. M. reports support for attending meetings and/or travel and payment/honoraria for presentations and educational events from Gilead. M. V. A. reports grants or contracts from Gilead and ViiV (paid to institution); payment or honoraria for lectures and educational events for Gilead and Janssen (paid to author and institution); payment or honoraria for educational events from ViiV and MSD (paid to institution); and support for attending meetings and/or travel from Angelini, Gilead, and Janssen (paid to author). P. G.-R. P. reports support for attending meetings and/or travel from Gilead and Angelini. P. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Sanofi (paid to author). R. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Gilead, ViiV, Merck Sharp & Dohme, and Theratechnologies (paid to author); payment for expert testimony from Gilead and ViiV (paid to author); support for attending meetings and/or travel from Gilead and Janssen (paid to author); and participation on a DSMB or advisory board for ViiV (paid to author). S. M. reports payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Pfizer, Gilead, Roche, Sobi, and MSD (paid to author), and participation on DSMBs or advisory boards for Pfizer, Gilead, and MSD (paid to author). V. E. reports consulting fees from Gilead, Janssen, and MSD (paid to author); payment or honoraria for lectures, presentations, speaker’s bureaus, manuscript writing, or educational events from Gilead and Janssen (paid to author); support for attending meetings and/or travel from Gilead (paid to author); and participation on DSMBs or advisory boards for Gilead, Janssen, and Synairgen (paid to author). None of the listed potential conflicts are related to this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)