Clinical Trial for Bradykinin Inhibition in Adults Hospitalized with Serious COVID-19

  • Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)
  • Total publications:1 publications

Grant number: 2020/04522-5

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2022
  • Known Financial Commitments (USD)

    $73,624.43
  • Funder

    Fundação de Amparo à Pesquisa do Estado de São Paulo [São Paulo Research Foundation] (FAPESP)
  • Principle Investigator

    Pending
  • Research Location

    Brazil, Americas
  • Lead Research Institution

    Universidade Estadual de Campinas
  • Research Category

    Therapeutics research, development and implementation

  • Research Subcategory

    Clinical trial (unspecified trial phase)

  • Special Interest Tags

    Gender

  • Study Subject

    Clinical

  • Clinical Trial Details

    Randomized Controlled Trial

  • Broad Policy Alignment

    Pending

  • Age Group

    Adults (18 and older)

  • Vulnerable Population

    Unspecified

  • Occupations of Interest

    Unspecified

Abstract

The pandemic of the new severe acute respiratory syndrome virus (SARS-CoV-2) has already been confirmed in more than 330 thousand people, being responsible for more than 14 thousand deaths worldwide (World Health Organization - official data of 23 March 2020). The current treatment for severe cases is based on respiratory support, use of a variety of antibiotics with possible extracorporeal oxygenation; however, the results are still unsatisfactory. Researchers have shown that the virus binds to Angiotensin-Converting Enzyme 2 (ECA2) to gain access to cells. This enzyme is essential in the inactivation of Angiotensin II (ANGII) and bradykinin. The accumulation of bradykinin in the lungs is a common effect after the use of ACE inhibitors with a consequent increase in cough. In studies with animal models, inactivation of ACE2 leads to severe pneumonitis after administration of lipopolysaccharides (LPS) and inhibition of bradykinin completely restores lung function and structure. As pneumonia is the most intense condition and a marker of disease progression, our hypothesis is that the increase in bradykinin is the main link between SARS-CoV-2 infection and ACE2 inhibition resulting in a severe respiratory syndrome. OBJECTIVE: To evaluate the efficacy of two pharmacological inhibitors of bradykinin, the C1 esterase / kallikrein inhibitor (Berinert®, CSL Behring GmbH) and the bradykinin receptor 2 inhibitor, icatibant (Firazyr®, Shire) in critically ill patients hospitalized for SARS -CoV-2. METHODOLOGY: This is an open randomized clinical trial to be carried out at Hospital de Clínicas, Universidade Estadual de Campinas, Brazil. One hundred and eighty patients will be divided in a 1: 1: 1 ratio to receive: i, the basic support established by published clinical trials, which include oxygen support, invasive and non-invasive mechanical ventilation, use of antibiotics, use of vasopressors and therapy renal support; or, ii, Berinert, 20 U / Kg intravenously, one dose on the day of inclusion in the study and one dose on the fourth day; patients in this group will receive the same basic support procedure offered to the control group; iii, Firazyr, 30 mg subcutaneously 8/8 h for four days; patients in this group will receive the same basic support procedure offered to the control group. The primary end points are, complete recovery with hospital discharge or death; monitoring will be done for 28 days. The inclusion criteria will be: men and women aged 18 years or older with positive RT-PCR for SARS-CoV-2; pneumonia confirmed by computed tomography (CT) of the chest; oxygen saturation in ambient air of 94% or less. Exclusion criteria: Pregnant or lactating women; patients with severe liver disease (alanine aminotransferase and / or aspartate aminotransferase> 5x above normal); severe nephropathy (kidney transplant or dialysis), HIV infection, cancer, hereditary angioedema, other immunodeficiencies, past myocardial ischemic disease, past thromboembolic disease. All study patients and / or their relatives will be informed about the research objectives and risks and should read and sign the Informed Consent Form.

Publicationslinked via Europe PMC

Last Updated:37 minutes ago

View all publications at Europe PMC

Evaluation of the efficacy and safety of icatibant and C1 esterase/kallikrein inhibitor in severe COVID-19: study protocol for a three-armed randomized controlled trial.