Trial reportEuropean journal of clinical investigation2022
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.
Trial report in European journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- 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.European journal of clinical investigation · 2022Trial
- Lock out: targeting TMPRSS2 to block influenza and coronaviruses.Journal of virology · 2026Review
- A Double-Edged Sword: Extracellular Serine Proteases as Facilitators of Infection and Mediators of Immunity.Molecules (Basel, Switzerland) · 2026Review
- Searching for Novel Antiviral Agents as COVID19 Treatments: Guanidino Diaryl Thioureas.ChemMedChem · 2026Article
- SARS-CoV-2 pseudoparticles preferentially infect ectoderm in human embryonic tissues.Frontiers in cell and developmental biology · 2026Article
- Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025Review
- An orally available MNature communications · 2025Article
- Trypstatin as a Novel TMPRSS2 Inhibitor with Broad-Spectrum Efficacy against Corona and Influenza Viruses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From N-0385 to N-0920: Unveiling a Host-Directed Protease Inhibitor with Picomolar Antiviral Efficacy against Prevalent SARS-CoV-2 Variants.Journal of medicinal chemistry · 2025Article
- Potential Broad-Spectrum Antiviral Agents: A Key Arsenal Against Newly Emerging and Reemerging Respiratory RNA Viruses.International journal of molecular sciences · 2025Review
- TMPRSS2 as a Key Player in Viral Pathogenesis: Influenza and Coronaviruses.Biomolecules · 2025Review
- Article
- Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.International journal of molecular sciences · 2024Review
- Recent advances in the discovery and development of drugs targeting the kallikrein-kinin system.Journal of translational medicine · 2024Review
- Clinical development of antivirals against SARS-CoV-2 and its variants.Current research in microbial sciences · 2024Review
- The KINETIC phase 2 randomized controlled trial of oral pamapimod-pioglitazone in non-critically ill COVID-19 inpatients.iScience · 2023Article
- Expression of TMPRSS2 is up-regulated by bacterial flagellin, LPS, and Pam3Cys in human airway cells.Life science alliance · 2023Article
- Aprotinin-Drug against Respiratory Diseases.International journal of molecular sciences · 2023Review
- Synergism of interferon-beta with antiviral drugs against SARS-CoV-2 variants.The Journal of infection · 2022Article
- As the virus evolves, so too must we: a drug developer's perspective : We need a new paradigm in searching for next-generation countermeasures.Virology journal · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSARS-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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.