eFigure. Randomization of Participants
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Cheng M, Fowler R, Murthy S, Pinto R, Sheehan NL, Tseng A. Remdesivir in Patients With Severe Kidney Dysfunction: A Secondary Analysis of the CATCO Randomized Trial. JAMA Netw Open. 2022;5(8):e2229236. doi:10.1001/jamanetworkopen.2022.29236
Remdesivir is a broad-spectrum antiviral that reduces hospitalization and may decrease mortality among noncritically ill inpatients with COVID-19.1,2 Remdesivir is not recommended for use in patients with an estimated glomerular filtration rate (eGFR) less than 30 mL/min1.73 m2 owing to the presence of excipients3 that may accumulate in kidney dysfunction and worsen kidney or hepatic outcomes.4
The Canadian Treatments for COVID-19 (CATCO) trial randomized patients to remdesivir or standard care between August 1, 2020, and April 1, 2021, as part of the global Solidarity trial.5 CATCO did not have kidney function–based exclusion criteria. We report on patients with impaired kidney function at baseline as a post hoc analysis to examine the risk of kidney or hepatic toxic effects with remdesivir administration.
Details of CATCO are presented elsewhere.5 This study was approved by all ethics committees and followed the CONSORT reporting guideline. Patients with impaired kidney function (eGFR <30 mL/min/1.73 m2 at randomization)6 received open-label remdesivir or best-quality supportive care (eFigure in Supplement 1). The trial protocol is available in Supplement 2. Lyophilized remdesivir was diluted and administered intravenously with a loading dose of 200 mg on day 1, followed by daily 100-mg doses for 9 days or until discharge. There was no dose adjustment for baseline kidney dysfunction or dialysis. Adverse events were reported by clinical staff.
We report all-cause mortality (unadjusted and adjusted for sex and baseline eGFR), adverse events, incidence of new ventilation or hemodialysis as proportions, and outcomes of day 5 eGFR and alanine aminotransferase levels, using medians (IQRs). There were no a priori levels of significance established. Given baseline imbalance, analysis of covariance was performed for the change in eGFR, adjusting for baseline eGFR. As sensitivity analysis, we report the results of binary outcomes for all patients in the main trial with eGFR 60 mL/min/1.73 m2, with 2-sided P values obtained through χ2 tests. All analyses were performed in SAS, version 9.4 (SAS Institute Inc).
Of 1281 patients, 59 (remdesivir, 34; standard care, 25) had a baseline eGFR less than 30 mL/min/1.73 m2; median age was 74 (IQR, 63-86) years (Table 1). There were imbalances between the groups, with more men and a lower median eGFR at baseline in the standard-care group. At baseline, few patients were undergoing hemodialysis; median eGFR was 18.9 (IQR, 10.2-24.2) mL/min/1.73 m2 across groups.
The median duration of remdesivir administered in the intervention arm was 10 (IQR, 6-10) days (mean, 8.2 days). There were no significant differences in key outcomes between groups (Table 2). Adjustment for sex and baseline eGFR did not change mortality outcomes (odds ratio, 0.74; 95% CI, 0.23-2.40). Analysis of covariance for change in eGFR showed no significant difference between groups. For patients with eGFR less than 60 mL/min/1.73 m2 (n = 248) at randomization, there was no significant difference between those receiving remdesivir (n = 122) or standard care (n = 126) in hospital mortality (35.2% vs 42.1%; P = .26), new mechanical ventilation (10.6% vs 15.7%; P = .27), or new dialysis (6.2% vs 5.0%; P = .70).
In patients with eGFR less than 30 mL/min/1.73 m2 at baseline who received remdesivir, there was no increased risk of transaminitis or toxic kidney effects at day 5. There was also no significant difference in the need for invasive mechanical ventilation or new dialysis, or mortality. This study is limited by small numbers and baseline imbalance between groups. These findings suggest that remdesivir can be safely administered in patients with kidney dysfunction, balancing possible risks and benefits. The need for assessing kidney function in the absence of clinical suspicion before and during outpatient administration of remdesivir can be questioned.
Accepted for Publication: July 13, 2022.
Published: August 29, 2022. doi:10.1001/jamanetworkopen.2022.29236
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Cheng M et al. JAMA Network Open.
Corresponding Author: Srinivas Murthy, MD, CM, MHSc, Faculty of Medicine, University of British Columbia, 4500 Oak St, Vancouver, BC, V6H 3V4 (email@example.com).
Author Contributions: Drs Murthy and Pinto had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Cheng, Fowler, Murthy.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Fowler, Murthy.
Critical revision of the manuscript for important intellectual content: Cheng, Fowler, Pinto, Sheehan, Tseng.
Statistical analysis: Fowler, Murthy, Pinto.
Obtained funding: Cheng, Fowler, Murthy.
Administrative, technical, or material support: Cheng, Fowler.
Supervision: Fowler, Murthy.
Conflict of Interest Disclosures: Dr Cheng reported receiving grants from the Canadian Institutes of Health Research and McGill Interdisciplinary Initiative in Infection and Immunity during the conduct of the study, fees (stock options) from GEn1E Lifesciences and Nomic Bio as a member of their scientific advisory boards, fees (equity) from Kanvas Biosciences as a cofounder of the company, consulting fees (honoraria) from Astra Zeneca, and research support from Cidara Therapeutics Scynexis Inc and Amplyx Pharmaceutics outside the submitted work. Dr Fowler reported receiving grants from the Canadian Institutes of Health Research during the conduct of the study. Dr Murthy reported receiving grants from Canadian Institutes of Health Research during the conduct of the study. Dr Sheehan reported receiving personal fees from Pfizer Canada, and personal fees from Merck Canada outside the submitted work. Dr Tseng reported personal consulting fees from Gilead Canada and personal fees from Pfizer Canada outside the submitted work. No other disclosures were reported.
Funding/Support: Funding support was received from the Canadian Institutes of Health Research.
Role of the Funder/Sponsor: The funding organization had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 3.