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Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial

2024; Oxford University Press; Volume: 79; Issue: 5 Linguagem: Inglês

10.1093/cid/ciae333

1537-6591

Meghan E. Sise, Jose Ramon Santos, Jason D. Goldman, Katherine R. Tuttle, J. Pedro Teixeira, A. F. Seibert, Yiannis Koullias, Joe Llewellyn, S. P. Regan, Yang Zhao, Hailin Huang, Robert H. Hyland, Anu Osinusi, Helen Winter, Rita Humeniuk, Henry N. Hulter, Robert Gottlieb, Dahlene N. Fusco, Rita Birne, Fernando F. Stancampiano, Claudia R. Libertin, Catherine B. Small, Markus Plate, Mark McPhail, Rosa Ballesteros, Rita Birne, Luís Malheiro, Gil Silva, João Paulo Correia, Ana Carlota Vida, André Silva, Antonio Carujo, Moncef Belhassen‐García, Jordi Carratala Fernandez, Gabriela Abelenda-Alonso, Josep M. Cruzado, Alexander Rombauts, Diego Sandoval, Miguel García Deltoro, Fransesc Puchades Gimeno, Neus Gómez‐Muñoz, Maria Martínez Roma, Juan Horcajada Gallego, Castañeda Pablo, Padilla Urrea Silvia, Rial Crestelo Sergio, Santos Fernandez David, Ramon Jose, Susanna Benet, Rosa Benítez, Carmen Bracke, Anna Chamorro, Sergio España, Fredzzia Graterol, Gemma Lladós, C. López, Lourdes Mateu, Roger Paredes, Boris Rebollo, Alba Romero, Laura Soldevila, Elena Abad, Anna Chamorro, Alba San José, Álex Soriano, Mark McPhail, Nicholas Medjeral‐Thomas, Suzana Margareth Lobo, Igor Z. Abolnik, Anjali Acharya, Leland Allen, Keith Bellovich, Mary Jane Burton, Miriam L. Cameron, Gerard J. Criner, Lii-Yoong H Criner, Joseph Lambert, Marium Rashid, Heidi Shore-Brown, George A. Diaz, David W. Dougherty, Nathaniel Erdmann, Dahlene N. Fusco, Jason D. Goldman, William R. Berrington, Christine M. Logar, Nidyanandh Vadivel, Allison Everett, Gonzalez Suarez Maria Lourdes, Robert Gottlieb, Mezgebe Berhe, Gates B. Colbert, Christopher Hebert, Ankit Mehta, Cedric W. Spak, Lorie Estrada, Richard Vargas, Jennifer H. Choe, Alex Pham, Lynn Mason, Catherine Tallmadge, Ariana Braddom, M. K. Nicholas, Aayla K. Jamil, Ashley McAllister, Christina Guerra, Teena Sam, Edilia Solis, Deepa Gotur, Munish Goyal, Farrukh M. Koraishy, Brett Laurence, Vinay Malhotra, Luis Manrique, James A. McKinnell, Blaithin A. McMahon, Ruth Campbell, Caryn G. Morse, Jesús Navarro, Luis Ostrosky, Bela Patel, Carolyn Z. Grimes, María Hernández, Mehriban Mammadova, Laura Nielsen, Virginia Umana, Tobias Pusch, Philip A. Robinson, Arun J. Sanyal, Harry Schrager, Jason Mallada, A. F. Seibert, Marc Siegel, Meghan E. Sise, Jihad Slim, Catherine B. Small, Peruvemba Sriram, Fernando F. Stancampiano, J. Pedro Teixeira, Krystle D. Apodaca, Michelle Harkins, Amy Cunningham, Katherine R. Tuttle,

SARS-CoV-2 and COVID-19 Research

Abstract Background Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. Methods In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. Results Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P = .61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function. Conclusions Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment. Clinical Trials Registration EudraCT 2020-005416-22; Clinical Trials.gov NCT04745351.