Length of hospital and intensive care unit stay in patients with invasive candidiasis and/or candidemia treated with rezafungin: a pooled analysis of two randomised controlled trials.

Autor: Honoré PM; Intensive Care Department, CHU UCL Namur Godinne, UCL Louvain Medical School, 1, Avenue G Therasse, 5530, Yvoir, Belgium. Patrick.Honore@CHUUCLNamur.UClouvain.be., Bassetti M; Department of Health Sciences, University of Genoa, and Istituto Di Ricovero E Cura a Carattere, Ospedale Policlinico San Martino, Genoa, Italy., Cornely OA; Institute for Translational Research, University of Cologne, and Department I of Internal Medicine, Cologne, Germany.; University Hospital Cologne, and German Centre for Infection Research (DZIF), Bonn-Cologne partner site, Cologne, Germany., Dupont H; Anesthesiology and Critical Care Medicine Department, University Hospital Amiens Picardie, Amiens, France., Fortún J; Ramón y Cajal University Hospital, CIBERINFEC, IRYCIS, Madrid, Spain., Kollef MH; Division of Pulmonary and Critical Care Medicine, Washington University, St Louis, MO, USA., Pappas P; Division of Infectious Diseases, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Pullman J; Clinical Research, Mercury Street Medical, Butte, MT, USA., Vazquez J; Division of Infectious Diseases, Department of Medicine, Medical College of Georgia/Augusta University, Augusta, GA, USA., Bielicka I; Mundipharma Research Ltd, Cambridge, UK., Dickerson S; Mundipharma Research Ltd, Cambridge, UK., Manamley N; Mundipharma Research Ltd, Cambridge, UK., Sandison T; Clinical Development, Cidara Therapeutics, Inc, San Diego, CA, USA., Thompson GR; Division of Infectious Diseases, Department of Internal Medicine, and Department of Medical Microbiology and Immunology, University of California Davis Medical Center, Sacramento, CA, USA.
Jazyk: angličtina
Zdroj: Critical care (London, England) [Crit Care] 2024 Nov 11; Vol. 28 (1), pp. 361. Date of Electronic Publication: 2024 Nov 11.
DOI: 10.1186/s13054-024-05152-2
Abstrakt: Background: Invasive candidiasis/candidemia (IC/C) is associated with a substantial health economic burden driven primarily by prolonged hospital stay. The once-weekly IV echinocandin, rezafungin acetate, has demonstrated non-inferiority to caspofungin in the treatment of IC/C. This paper reports a post hoc pooled exploratory analysis of length of stay (LoS) for hospital and intensive care unit (ICU) stays in two previously published clinical trials (ReSTORE [NCT03667690] and STRIVE [NCT02734862], that compared rezafungin with daily IV caspofungin (stable patients in the caspofungin group who met relevant criteria could step down to fluconazole after 3 days or more).
Methods: LoS outcomes were analysed descriptively in the pooled modified intention to treat (mITT) population (all patients who had a documented Candida infection in line with trial requirements and received at least one dose of study drug). In addition, to adjust for an imbalance between treatment groups in the proportion receiving mechanical ventilation at baseline, a generalised linear model with mechanical ventilation as a binary covariate was applied. Responses to an exploratory question in the phase 3 trial on possible earlier discharge with weekly rezafungin are also reported.
Results: 294 patients were included (rezafungin 139, caspofungin 155), of whom 126 (43%) had ICU admission. Patients treated with rezafungin had a numerically shorter LoS than with caspofungin in all analyses. Mean total LoS was 25.2 days, vs 28.3 days with caspofungin, and mean ICU LoS was 16.1 vs 21.6 days for rezafungin and caspofungin, respectively. After adjustment for mechanical ventilation status the difference in ICU LoS was 4.1 days, a relative difference of 24% (95% CI -11%, 72%). Physicians would have considered earlier discharge for 16% of patients (30/187) with weekly rezafungin, an average of 5-6 days earlier.
Conclusions: Rezafungin may enable shorter hospital and ICU LoS in IC/C compared with daily IV caspofungin, with accompanying savings in resource use. Further research is needed to confirm this in the real-world setting.
Trial Registration: NCT03667690 (ReSTORE; September 12, 2018); NCT02734862 (STRIVE; April 12, 2016).
Competing Interests: Declarations Data and availability of materials Data supporting the findings of this study are available on request from Sara Dickerson, Sara.Dickerson@mundipharma.com. Ethics approval and consent to participate Both the STRIVE and ReSTORE trials were in conducted in accordance with current country and local regulations, the International Conference on Harmonisation Good Clinical Practice, and the Declaration of Helsinki. Ethics committees or institutional review boards at participating sites approved the protocols and all amendments. All patients, or their legally authorised representative, provided written informed consent. Consent for publication Not applicable. Competing interests PMH reports grants or contracts from Baxter, Cytosorbents, and Pfizer; consulting fees from Baxter, Cytosorbents, and Pfizer; honoraria from Baxter, and Cytosorbents; and support for attending meetings from Mundipharma, and Pfizer, outside of the submitted work. MB reports honoraria from and membership of data safety monitoring board or advisory board for Angelini, Cidara, Gilead, Menarini, MSD, Pfizer, and Shionogi, outside of the submitted work. OAC reports grants or contracts from Amplyx, Basilea, Bundesministerium für Bildung und Forschung, Cidara, German Center for Infection Research, European Union Directorate-General for Research and Innovation (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, and Scynexis; consulting fees from AbbVie, Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, IQVIA, Janssen, Matinas, MedPace, Menarini, Molecular Partners, Noxxon, Octapharma, Pardes, Pfizer, Pharma Support America, Scynexis, and Seres; honoraria from Abbott, AbbVie, Al-Jazeera Pharmaceuticals, Astellas, Gilead, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Noscendo, Pfizer, and Shionogi; payment for expert testimony from Cidara; data safety monitoring board or advisory board membership for Actelion, Allecra, Cidara, Entasis, IQVIA, Janssen, MedPace, Paratek, Pharma Support America, Pulmocide, Shionogi, and The Prime Meridian Group; a patent at the German Patent and Trade Mark Office (DE 10 2021 113 007.7); stocks from CoRe Consulting; outside of the submitted work. HD reports consulting fees from Pfizer, Gilead, MSD, Mundipharma, Shionogi, Viatris, outside of the submitted work. JF was an advisor/consultant and received grant support and honoraria for talks on behalf of Astellas Pharma, Gilead Sciences, Merck Sharp & Dohme and Pfizer, outside of the submitted work. MK reports grants from Barnes-Jewish Hospital Foundation and consulting fees from Merck, Pfizer, and Shionogi, outside of the submitted work. PP reports grants from Astellas, Gilead, Scynexis, and Cidara; fees for scientific advisory board from F2G, Matinas, TFF, Basilea outside of the submitted work. JP Reports no conflict of interest. JV reports consulting fees from and membership of data safety monitoring board or advisory board for F2G and consulting fees from Cidara and Scynexis, outside of the submitted work. IB and NM report being employees of Mundipharma. TS reports being an employee of and holding stocks in Cidara Therapeutics. GRT reports grants and consulting fees from Amplyx, Astellas, Cidara, F2G, and Manye; grants from Merck; and data safety monitoring board membership for Pfizer, outside of the submitted work.
(© 2024. The Author(s).)
Databáze: MEDLINE
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