COVID-19 Drugs: Researchers From Boston Children's Hospital Initiate Randomized Clinical Trial Of Pulmozyme To Treat Severe COVID-19 Patients
: Researchers from the Boston Children's Hospital and Brigham and Women's Hospital have launched a randomized, placebo-controlled clinical trial of dornase alfa (Pulmozyme) in patients with severe COVID-19 pneumonia and respiratory failure requiring mechanical ventilation.
The protein Dornase alfa (proprietary name Pulmozyme from Genentech) is a highly purified solution of recombinant human deoxyribonuclease I (rhDNase), an enzyme which selectively cleaves DNA. Dornase alfa hydrolyzes the DNA present in sputum/mucus of cystic fibrosis patients and reduces viscosity in the lungs, promoting improved clearance of secretions. This protein based therapeutic agent is produced in Chinese hamster ovary cells
Dornase alfa, also called DNase 1, is US FDA-approved for patients with cystic fibrosis, to break up thick mucus secretions and prevent lung infections.
The new study aims to enroll 60 adults and children (over age 3) admitted to intensive care units.
The clinical trial is supported by the Massachusetts Consortium on Pathogen Readiness, and the drug is being provided by Genentech, a member of the Roche Group, which is also providing supplementary financial support.
Dr Benjamin Raby, MD., MPH., Chief and Principal Investigator, Division of Pulmonary Medicine, Boston Children's Hospital told Thailand Medical News,
“We hope this drug, which is known to be safe, will help reduce the inflammation that contributes to worsening respiratory distress in COVID-19.”
This new 18-month study will randomize patients to twice-daily nebulized dornase alfa or placebo (a saline solution) within 48 hours after intubation and placement on a ventilator.
All research treatments will be given via the ventilator tubing, twice a day for up to 28 days. Researchers will then monitor both groups for up to 28 days, or until patients are no longer receiving mechanical ventilation, whichever is sooner.
As part of the research, neither the researchers nor the patients (and families) will know which treatment is being given.
The major outcome of interest is the number of patients in each group who are alive and ventilator-free 28 days after treatment. Other measures will include airway resistance to breathing, lung compliance (the lungs' ability to stretch and expand), blood oxygenation, and length of stay in the ICU and hospital.
It has been seen that some patients with COVID-19 pneumonia produce large amounts of thick mucus that can make effective delivery of oxygen by mechanical ventilation more challenging.
It has been proven that Dornase alfa is an effective mucolytic, able to soften mucus and promote its clearance from the airways. In addition, dornase alfa may be able to reduce lung inflammation promoted by neutrophil extracellular traps, or NETs.
These NETs are webs of DNA and toxic protein released by neutrophils, first responders in the immune system, in an excessive effort to entrap invading microbes.
Also NETs are known t
o produce dangerous blood clots such as those that form in COVID-19 patients, and are known, in general, to contribute to blood clots in the lung capillaries, inflammation, and lung injury.
Dr Denisa Wagner, PhD, of the Program in Cellular and Molecular Medicine at Boston Children's Hospital, who helped to initiate the new trial, has been studying NETs and their role in unwanted clot formation and fibrosis (thickening and scarring of tissue) for more than a decade.
Dr Wagner said, "Preclinical studies by several groups, including ours at Boston Children's Hospital, have found that DNase 1 improved outcome in lung injury models and thrombotic models mimicking events that occur frequently in COVID-19, such as deep vein thrombosis, stroke and microvascular thrombosis."
He further added, "This suggests to us that treatment with DNase could be beneficial in severe lung injury observed in COVID-19."
Even though this research is limited to the lung, it's hypothesized that NETs contribute to coagulopathies seen with COVID-19 elsewhere in the body.
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