Aprotinin treatment against SARS-CoV-2: A randomized phase III study to evaluate the safety and efficacy of a pan-protease inhibitor for moderate COVID-19.

Autor: Redondo-Calvo FJ; Department of Anesthesiology and Critical Care Medicine, University General Hospital, Ciudad Real, Spain.; Department of Medical Sciences (Pharmacology), School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain.; School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain., Padín JF; Translational Research Unit, University General Hospital of Ciudad Real, Ciudad Real, Spain., Muñoz-Rodríguez JR; Department of Medical Sciences (Pharmacology), School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain.; School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain., Serrano-Oviedo L; School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain., López-Juárez P; School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain., Porras Leal ML; Department of Internal Medicine, University General Hospital of Ciudad Real, Ciudad Real, Spain., González Gasca FJ; Department of Medical Sciences (Pharmacology), School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain.; Department of Internal Medicine, University General Hospital of Ciudad Real, Ciudad Real, Spain., Rodríguez Martínez M; Department of Pharmacy, University General Hospital of Ciudad Real, Ciudad Real, Spain., Pérez Serrano R; Department of Pharmacy, University General Hospital of Ciudad Real, Ciudad Real, Spain., Sánchez Cadena A; Department of Pharmacy, University General Hospital of Ciudad Real, Ciudad Real, Spain., Bejarano-Ramírez N; Department of Medical Sciences (Pharmacology), School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain.; Department of Paediatrics, University General Hospital of Ciudad Real, Ciudad Real, Spain., Muñoz Hornero C; Department of Internal Medicine, General Hospital of Puertollano, Puertollano, Spain., Barberá Farré JR; Department of Internal Medicine, University General Hospital of Alcazar de San Juan, Alcazar de San Juan, Spain., Domínguez-Quesada I; Department of Internal Medicine, University General Hospital of Alcazar de San Juan, Alcazar de San Juan, Spain., Sepúlveda Berrocal MA; Department of Internal Medicine, University General Hospital of Toledo, Toledo, Spain., Villegas Fernández-Infantes MD; Department of Internal Medicine, University General Hospital of Ciudad Real, Ciudad Real, Spain., Manrique Romo MI; Department of Internal Medicine, University General Hospital of Ciudad Real, Ciudad Real, Spain., Parra Comino Á; Translational Research Unit, University General Hospital of Ciudad Real, Ciudad Real, Spain., Pérez-Ortiz JM; Department of Medical Sciences (Pharmacology), School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain.; School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain., Gómez-Romero FJ; Department of Medical Sciences (Pharmacology), School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain.; School of Medicine at Ciudad Real, University of Castilla-La Mancha, Ciudad Real, Spain.
Jazyk: angličtina
Zdroj: European journal of clinical investigation [Eur J Clin Invest] 2022 Jun; Vol. 52 (6), pp. e13776. Date of Electronic Publication: 2022 Apr 05.
DOI: 10.1111/eci.13776
Abstrakt: Background: SARS-CoV-2 virus requires host proteases to cleave its spike protein to bind to its ACE2 target through a two-step furin-mediated entry mechanism. Aprotinin is a broad-spectrum protease inhibitor that has been employed as antiviral drug for other human respiratory viruses. Also, it has important anti-inflammatory properties for inhibiting the innate immunity contact system.
Methods: This was a multicentre, double-blind, randomized trial performed in four Spanish hospitals comparing standard treatment versus standard treatment + aprotinin for patients with COVID-19 between 20 May 2020 and 20 October 2021. The primary efficacy outcomes were length of hospital stay and ICU admission. The secondary endpoints were each of the primary efficacy outcomes and a composite of oxygen therapy, analytical parameters and death. Safety outcomes included adverse reactions to treatment during a 30-day follow-up period. Treatment was given for 11 days or till discharge.
Results: With almost identical analytical profiles, significant differences were observed in treatment time, which was 2 days lower in the aprotinin group (p = .002), and length of hospital admission, which was 5 days shorter in the aprotinin group (p = .003). The incidence of discharge was 2.19 times higher (HR: 2.188 [1.182-4.047]) in the aprotinin group than in the placebo group (p = .013). In addition, the aprotinin-treated group required less oxygen therapy and had no adverse reactions or side effects.
Conclusion: Inhaled aprotinin may improve standard treatment and clinical outcomes in hospitalized patients with COVID-19, resulting in a shorter treatment time and hospitalization compared with the placebo group. The administration of aprotinin was safe.
(© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)
Databáze: MEDLINE
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