Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome

Article Details

Authors
Steven H Abman, Nicholas R Fox, M Ibrahim Malik, Sneha S Kelkar, Shelby L Corman, Sanika Rege, Jenna Bhaloo, Rachel Shah, Ren-Jay Shei, Dana Saporito, Nisreen Shamseddine, Erik DeBoer, George J Wan, on behalf of the NOTICE Study Investigators

Article Type
Original Research

DOI
10.7573/dic.2022-1-4

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Abstract

Background: Inhaled nitric oxide (iNO) has been studied in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 when it may be too late to impact disease course. This article aims to describe real-world iNO use and outcomes in patients with COVID-19 with mild-to-moderate ARDS in the United States.

Methods: This was a retrospective medical chart review study that included patients who were ≥18 years old, hospitalized for COVID-19, met the Berlin ARDS definition, received iNO for ≥24 hours continuously during hospitalization, and had a partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F ratio) of >100 to ≤300 mmHg at iNO initiation. Outcomes included oxygenation parameters, physician-rated Clinical Global Impression–Improvement (CGI-I) scale scores, and adverse events. Response to iNO was defined as >20% improvement in P/F ratio.

Results: Thirty-seven patients at six sites were included. A P/F ratio of ≤100 was the most common reason for exclusion (n=146; 83% of excluded patients). The mean P/F ratio (SD) increased from 136.7 (34.4) at baseline to 140.3 (53.2) at 48 hours and 151.8 (50.0) at 72 hours after iNO initiation. The response rate was 62% (n=23). During hospitalization, no patient experienced adverse events, including methemoglobinaemia, airway injury, or worsening pulmonary oedema associated with iNO. At discharge, 54.0% (n=20) of patients improved or remained stable according to the CGI-I.

Conclusion: In patients hospitalized with COVID-19 and mild-to- moderate ARDS, iNO was associated with improvement in the P/F ratio with no reported toxicity. This study provides additional evidence supporting a favourable benefit–risk profile for iNO in the treatment of mild-to-moderate ARDS in patients with COVID-19 infection.

Keywords: acute respiratory distress syndrome (ARDS), COVID-19, inhaled nitric oxide, P/F ratio, real-world.

Citation: Abman SH, Fox NR, Malik MI, Kelkar SS, Corman SL, Rege S, Bhaloo J, Shah R, Shei R-J, Saporito D, Shamseddine N, DeBoer E, Wan GJ, on behalf of the NOTICE Study Investigators. Real-world use of inhaled nitric oxide therapy in patients with COVID-19 and mild-to-moderate acute respiratory distress syndrome. Drugs Context. 2022;11:2022-1-4. https://doi.org/10.7573/dic.2022-1-4

Contributions: SHA, SSK, SLC, DS, NS, ED and GJW designed the study and developed the protocol. JB and RS recruited investigators. SHA, NRF and MIM collected the data, and SR, SSK and R-JS analysed the data. SSK and SLC drafted the manuscript. All authors edited and approved the final version before submission. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Disclosure and potential conflicts of interest: SSK, SLC, SR, JB and RS were employees of OPEN Health during the course of the study. OPEN Health received consulting fees from Mallinckrodt Pharmaceuticals, which funded the study. R-JS, DS, NS, ED, and GJW were employees of Mallinckrodt Pharmaceuticals while the study was being conducted. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2022/03/dic.2022-1-4-COI.pdf

Acknowledgements: Editorial support was provided by Christina DuVernay of OPEN Health.

Funding declaration: The study was funded by Mallinckrodt Pharmaceuticals.

Copyright: Copyright © 2022 Abman SH, Fox NR, Malik MI, Kelkar SS, Corman SL, Rege S, Bhaloo J, Shah R, Shei R-J, Saporito D, Shamseddine N, DeBoer E, Wan GJ, on behalf of the NOTICE Study Investigators. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0, which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission.

Correct attribution: Copyright © 2022 Abman SH, Fox NR, Malik MI, Kelkar SS, Corman SL, Rege S, Bhaloo J, Shah R, Shei R-J, Saporito D, Shamseddine N, DeBoer E, Wan GJ, on behalf of the NOTICE Study Investigators. https://doi.org/10.7573/dic.2022-1-4. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0.

Article URL: https://www.drugsincontext.com/real-world-use-of-inhaled-nitric-oxide-therapy-in-patients-with-covid-19-and-mild-to-moderate-acute-respiratory-distress-syndrome

Correspondence: Sneha S Kelkar, OPEN Health, 4350 East-West Highway, Suite 1100, Bethesda, MA 20814, USA. Email: snehakelkar@openhealthgroup.com

Provenance: Submitted; externally peer reviewed.

Submitted: 27 January 2022; Accepted: 15 March 2022; Publication date: 11 April 2022.

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