Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial
Author:
Sise Meghan E1, Santos Jose Ramon2, Goldman Jason D34, Tuttle Katherine R5, Teixeira J Pedro6, Seibert Allan F7, Koullias Yiannis8, Llewellyn Joe8, Regan Sean8, Zhao Yang8, Huang Hailin8, Hyland Robert H8, Osinusi Anu8, Winter Helen8, Humeniuk Rita8, Hulter Henry N9, Gottlieb Robert L1011, Fusco Dahlene N12, Birne Rita1314, Stancampiano Fernando F15, Libertin Claudia R15, Small Catherine B16, Plate Markus16, McPhail Mark J17, , Ballesteros Rosa, Birne Rita, Malheiro Luis, Silva Gil, Correia João Paulo, Vida Ana, Silva Andre, Carujo Antonio, Garcia Moncef Belhassen, Fernandez Jordi Carratala, Abelenda-Alonso Gabriela, Cruzado Josep M, Rombauts Alexander, Sandoval Diego A, Deltoro Miguel Garcia, Gimeno Fransesc Puchades, Gómez-Muñoz Neus, Roma Maria Martínez, Gallego Juan Horcajada, Pablo Castañeda, Silvia Padilla Urrea, Sergio Rial Crestelo, David Santos Fernandez, Jose Ramon, Benet Susanna, Benítez Rosa, Bracke Carmen, Chamorro Anna, España Sergio, Graterol Fredzzia, LLadós Gemma, López Cristina, Mateu Lourdes, Paredes Roger, Rebollo Boris, Romero Alba, Soldevila Laura, Abad Elena, Chamorro Anna, José Alba San, Viladomiu Alex Soriano, McPhail Mark, Medjeral-Thomas Nicholas, Lobo Suzana Margareth Ajeje, Abolnik Igor, Acharya Anjali, Allen Leland, Bellovich Keith A, Burton Mary Jane, Cameron Miriam, Criner Gerard J, Criner Lii-Yoong H, Lambert Joseph, Rashid Marium, Shore-Brown Heidi, Diaz George A, Dougherty David, Erdmann Nathaniel B, Fusco Dahlene, Goldman Jason D, Berrington William, Logar Christine, Vadivel Nidyanandh, Everett Allison, Maria Lourdes Gonzalez Suarez, Gottlieb Robert L, Berhe Mezgebe, Colbert Gates, Hebert Christopher, Mehta Ankit, Spak Cedric W, Estrada Lorie, Vargas Richard, Choe Jennifer, Pham Alex, Mason L Maria, Tallmadge Catherine, Braddom Ariana, Nicholas Maldonado, Jamil Aayla, McAllister Ashley, Guerra Christina, Sam Teena, Solis Edilia, Gotur Deepa, Goyal Munish, Koraishy Farrukh, Laurence Brett, Malhotra Vinay, Manrique Luis A, McKinnell James A, McMahon Blaithin, Campbell Ruth, Morse Caryn, Navarro Jesus, Ostrosky Luis, Patel Bela, Grimes Carolyn, Hernandez Maria, Mammadova Mehriban, Nielsen Laura, Umana Virginia, Pusch Tobias, Robinson Philip, Sanyal Arun J, Schrager Harry, Mallada Jason, Seibert Allan F, Siegel Marc, Sise Meghan, Slim Jihad, Small Catherine, Sriram Peruvemba, Stancampiano Fernando, Teixeira Joao Pedro, Apodaca Krystle D, Harkins Michelle S, Cunningham Amy G, Tuttle Katherine R
Affiliation:
1. Division of Nephrology, Massachusetts General Hospital , Boston, Massachusetts , USA 2. Fight Infections Foundation, Service of Infectious Diseases, Hospital Universitari Germans Trias i Pujol , Badalona , Spain 3. Swedish Center for Research and Innovation, Providence Swedish Medical Center , Seattle, Washington , USA 4. Division of Allergy and Infectious Diseases, University of Washington , Seattle, Washington , USA 5. Providence Medical Research Center, Providence Inland Northwest Health , Spokane, Washington , USA 6. Divisions of Nephrology and Pulmonary, Critical Care, and Sleep Medicine, University of New Mexico Hospital , Albuquerque, New Mexico , USA 7. Pulmonary Associates Research, Ascension Providence , Mobile, Alabama , USA 8. Gilead Sciences , Foster City, California , USA 9. Department of Medicine, University of California , San Francisco, California , USA 10. Department of Internal Medicine, Baylor University Medical Center , Dallas, Texas , USA 11. Baylor Scott & White Research Institute , Dallas, Texas , USA 12. Department of Medicine, Tulane University School of Medicine , New Orleans, Louisiana , USA 13. Department of Nephrology, Centro Hospitalar de Lisboa Ocidental , Lisbon , Portugal 14. NOVA Medical School , Lisbon , Portugal 15. Department of Internal Medicine, Mayo Clinic College of Medicine and Science , Jacksonville, Florida , USA 16. Department of Medicine, Division of Infectious Diseases, Weill Cornell Medicine , New York, New York , USA 17. Institute of Liver Studies, King's College Hospital , London , United Kingdom
Abstract
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.
Publisher
Oxford University Press (OUP)
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