Francisco Javier Redondo Calvo1,2,3, Juan Fernando Padín4, José Ramón Muñoz‐Rodríguez2,3, Leticia Serrano‐Oviedo3, Pilar López‐Juárez3, María Lourdes Porras Leal5, Francisco Javier González Gasca5,2, Marta Rodríguez Martínez6, Raúl Pérez Serrano6, Abraham Sánchez Cadena6, Natalia Bejarano2,7, Constanza Muñoz Hornero8, José Ramón Barberá Farré9, Inmaculada Domínguez‐Quesada9, María A. Sepúlveda Berrocal10, María Dolores Villegas Fernández‐Infantes5, María Isabel Manrique Romo5, A Comino4, José Manuel Pérez‐Ortiz2,3, Francisco Javier Gómez‐Romero2,3
1Department of Anesthesiology and Critical Care Medicine University General Hospital Ciudad Real Spain
2Department of Medical Sciences (Pharmacology) School of Medicine at Ciudad Real University of Castilla‐La Mancha Ciudad Real Spain
3Translational Research Unit University General Hospital of Ciudad Real Ciudad Real Spain
4Department of Medical Sciences (Pharmacology) School of Medicine at Ciudad Real University of Castilla-La Mancha Ciudad Real Spain
5Department of Internal Medicine University General Hospital of Ciudad Real Ciudad Real Spain
6Department of Pharmacy University General Hospital of Ciudad Real Ciudad Real Spain
7Department of Paediatrics University General Hospital of Ciudad Real Ciudad Real Spain
8Department of Internal Medicine General Hospital of Puertollano Puertollano Spain
9Department of Internal Medicine University General Hospital of Alcazar de San Juan Alcazar de San Juan Spain
10Department of Internal Medicine University General Hospital of Toledo Toledo Spain
Tóm tắt
AbstractBackgroundSARS‐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.MethodsThis 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.ResultsWith 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.ConclusionInhaled 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.
