Clinical Trial to Test Cystic Fibrosis Drug in Patients with Severe COVID-19 Pneumonia and Respiratory Failure

Harvard Medical School (Boston, MA, USA) researchers at Boston Children’s Hospital and Brigham and Women’s Hospital have begun testing an existing drug, dornase alfa, in patients with severe COVID-19 pneumonia and respiratory failure.

Dornase alfa, also known as DNase 1 or Pulmozyme, is FDA-approved for cystic fibrosis to break up thick mucus secretions and prevent lung infections. The drug may also break up neutrophil extracellular traps, or NETs, which scientists believe contribute to lung inflammation. NETs are webs of DNA and toxic protein that neutrophils - first-responder cells in the immune system - spew out to entrap microbes. NETs have a down side: They can produce dangerous blood clots in the lung, such as those that form in COVID-19 patients. These clots can contribute to lung inflammation and injury. Preclinical studies suggest that dornase alfa could benefit COVID-19 patients with severe lung injury. The new study will focus on the lung, as scientists hypothesize that NETs contribute to excess clotting seen elsewhere in the body in COVID-19.

The randomized, controlled clinical trial involves 60 adults and children over three years of age who require mechanical ventilation. The 18-month study will randomize patients to dornase alfa or placebo (a saline solution) soon after placement on a ventilator. Patients will receive twice-daily nebulized treatments through the ventilator tubing. The patients will be monitored for up to 28 days, or until they come off the ventilator, whichever is sooner. Neither the researchers nor the patients or their families will know which treatment is being given. The main outcome being tracked is how many patients in each group are alive and ventilator-free at 28 days. Other measures 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.

“We hope this drug, which is known to be safe, will help reduce the inflammation that contributes to worsening respiratory distress in COVID-19,” said the study's lead investigator, Benjamin Raby, the Leila and Irving Perlmutter Professor of Pediatrics at HMS and chief of pulmonary medicine at Boston Children’s.

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