Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial
Authors: Sise Meghan E , Santos Jose Ramon , Goldman Jason D , Tuttle Katherine R , Teixeira J Pedro , Seibert Allan F , Koullias Yiannis , Llewellyn Joe , Regan Sean , Zhao Yang , Huang Hailin , Hyland Robert H , Osinusi Anu , Winter Helen , Humeniuk Rita , Hulter Henry N , Gottlieb Robert L , Fusco Dahlene N , Birne Rita , Stancampiano Fernando F , Libertin Claudia R , Small Catherine B , Plate Markus , McPhail Mark J ,   for the REDPINE Investigators, 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 
Published: June 2024

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.