According to studies published at the ATS 2022 International Conference, the double-blind randomized placebo-controlled multicenter clinical trial STOP-COVID19 did not improve the clinical status of patients hospitalized with severe SARS-CoV-2 infection.
The study, which began in June 2020, took place in 14 hospitals in the UK, where participants were randomized to receive 25 mg of brensocateb or placebo per day for 28 days. One hundred and ninety patients received brensocatib and 214 received placebo.
All patients in the study were confirmed to have SARS-CoV-2 infection and at least one risk factor for severe COVID-19, such as the need for supplemental oxygen. Individuals on mechanical ventilation were excluded from the study. All participants received standard treatment.
“Such treatments that are currently available for the treatment of COVID-19, such as dexamethasone and antibodies against IL-6, reduce inflammation, but their effects are not primarily on neutrophils or neutrophilic inflammation, “said presentation author Holly Cair, Ph.D., MD, Dundee University School of Medicine, Dundee, UK.” We conducted a STOP-COVID test to test the hypothesis that direct -1 (DPP1) will provide additional benefits to patients with severe COVID-19 in addition to standard treatment ”.
Severe COVID-19 infection is primarily caused by an excessive and impaired immune response to the virus. A number of different immune cells, including neutrophils, are involved in this reaction. Neutrophils secrete enzymes and other substances that cause severe lung damage. Studies consistently show that high levels of neutrophil inflammation are associated with worse outcomes with COVID-19.
Brensocatib is an oral inhibitor of DPP1, the enzyme responsible for activating neutrophil serine proteases.
In STOP-COVID19, time to clinical improvement and time to discharge did not differ between groups. Mortality rates were 10.7 percent and 15.3 percent in the placebo and brenzocab groups, respectively. Oxygen utilization and new ventilation were also quantitatively greater in patients receiving brensocatib. Analysis of pre-defined subgroups based on age, sex, baseline severity, co-administration, and duration of symptoms confirmed the primary results. Adverse events were reported in 46.3 percent of patients taking placebo and 44.8 percent of patients taking brensocatib.
The researchers also conducted an additional study at two study sites to directly measure inflammation in patients receiving DPP1 inhibition or placebo. They observed a strong anti-inflammatory effect of DPP1 inhibition on protease neutrophil enzymes. The level of active elastase of blood neutrophils decreased on the eighth day in the treatment group and remained significantly lower until the 29th day.
“Although we did not find a beneficial effect from treatment in this population, these results are important for future efforts to target neutrophilic pneumonia. STOP-COVID19 is the largest completed study of DPP1 inhibition in humans, and we conducted a broad characterization of how DPP1 inhibition affects “Immune system response,” said Dr. Keir. “Using modern proteomics (studying the structure, function and interactions of proteins), we have already seen important changes in neutrophils with DPP1 inhibition that will help us better understand the potential role of this treatment in other diseases.”
One such disease is bronchiectasiswhere a phase 2 study published in 2020 found that brensocatib reduces the risk of exacerbations.
Abstract: A randomized, double-blind, placebo-controlled study of dipeptidyl peptidase-1 inhibition in hospitalized patients with COVID-19: the STOP-COVID19 trial
American Thoracic Society
Citation: In the STOP-COVID19 study, brencosacib did not improve the condition of patients with severe COVID-19 (2022, May 18), obtained May 18, 2022 from https://medicalxpress.com/news/2022-05-stop-covid19 -trial- brensocatib-condition-patients.html
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