Irish team begins clinical trial for drug therapy for severe Covid-19 infection

A clinical trial of a promising therapy for critically-ill Covid-19 patients in intensive care using a protein produced in the body has been initiated by a team at the Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin.

Alpha-1-antitrypsin is produced by the liver and released into the bloodstream which normally acts to protect the lungs from the destructive actions of common illnesses.

The team led by professors Gerry McElvaney and Ger Curley have published a paper on the science behind Alpha-1 antitrypsin, and why it is “a good candidate” for patients who require admission to intensive care. The paper was published by the American Journal of Respiratory and Critical Care Medicine.

It is described as the first "investigational medicine product trial to be approved in Ireland to test a therapy to treat Covid-19". It will be used to treat critically-ill patients, who are mechanically ventilated in ICU and have associated acute respiratory distress syndrome (Ards) – a debilitating condition arising in extreme coronavirus cases.

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Prof McElvaney underlined the importance of finding new therapies as cases continue to grow substantially throughout the world. More than 500 patients have been admitted to Beaumont, and nearly 50 patients required admission to intensive care.

“Current management of severe Covid-19 remains supportive, focusing on supplemental oxygen and ventilator support in the event of acute respiratory failure. Despite the implications for global health, the inflammatory characteristics of patients with Covid-19 are not yet fully understood,” he said.

A greater understanding of how the body’s inflammatory mechanisms are impacted by Covid-19 could open the door to several potential therapies including antiviral medications and “targeted immune-modulators” such as Alpha-1-antitrypsin.

"We know from in-hospital studies that many Covid-19 patients in ICU develop severe inflammation throughout the body with a disproportionately high rate of progression to Ards [acute respiratory distress syndrome]; acute renal failure, shock and heart arrhythmia," Prof Curley explained.

Inflammation

In a collaboration between RCSI’s Departments of Medicine and Critical Care and Anaesthesia, they are seeking to ascertain the type of inflammation affecting Covid-19 patients in ICU, and to determine whether there is a relationship between this type of inflammation and the need for intubation and mechanical ventilation. Initially 36 patients from hospitals in Dublin and Galway will be involved.

Their initial study indicates the key differentiating factor between patients with stable and severe disease was not the degree of increase in inflammatory proteins, but a decrease in levels of an anti-inflammatory protein “which indicates that the patients’ anti-inflammatory mechanisms were failing”, Prof Curley explained.

This finding suggested a therapy which augments the body’s own inflammation resolving mechanisms might have a positive impact. “Alpha-1 protects the airway from damage during acute pulmonary infection. It is also a potent anti-inflammatory and acts to protect the immune system,” he added.

This will be a randomised double blind placebo-controlled clinical trial in which neither participants nor clinicians know who is receiving a particular treatment, which is among the most reliable ways to evaluate a potential treatment.

If the researchers show that using Alpha-1 antitrypsin reduces damaging inflammation, they will lead a larger study to assess effects on mortality; time in ICU, time on a ventilator and time in hospital. The larger study would need to be international and recruit more than 300 patients.