A collaboration between researchers at CÚRAM, the SFI Research Centre based at NUI Galway, and industry partner Aerogen, the high-performance aerosol drug delivery company, has been established recently.

The project, costing more than €400,000, is focused on optimising the Aerogen Solo nebuliser for the delivery of Heparin into the lung of patients with COVID-19 induced Acute Respiratory Failure (ARDS).

Trials to begin in December 2020

Heparin is a compound that occurs in the body, which prevents blood clotting. The project will run until September 2021 and clinical patient trials are due to commence in December 2020.

Led by Professor John Laffey at CÚRAM, NUI Galway and Dr Ronan MacLoughlin at Aerogen, the project will determine the safety, efficacy and mechanisms of action of nebulised heparin in COVID-19 induced Acute Respiratory Failure.

The Aerogen Solo converts the liquid drug into a nebulised mist of consistently sized droplets that enable medication to get deep into the patients’ lung.

Recommended by multiple international COVID-19 guidance documents, Aerogen is the only globally available closed circuit aerosol drug delivery system that mitigates the transmission of patient generated infectious aerosol and delivers effective aerosol treatment.

Prof Laffey, professor of intensive care medicine at NUI Galway, consultant in intensive care medicine, Galway University Hospitals and CÚRAM investigator, said: “Disordered clotting in the lungs is a feature of COVID-19 induced ARDS. Heparin has specific potential benefits in Covid infection.

Inactivates the SARSCoV-2 virus

"It inactivates the SARSCoV-2 virus and prevents its entry into mammalian cells and appears likely to have a beneficial effect in these patients too, provided it can be safely and effectively delivered to the lungs.”

Standard treatment to reduce the risk of the formation of blood clots in the lungs can have substantial associated risks and side effects, such as major haemorrhage and intracerebral haemorrhage.

Nebulising heparin directly into the lung may improve the clotting disorder seen in COVID-19 induced severe respiratory failure, while potentially reducing the risk of serious side effects seen when heparin is given by traditional routes.

Effective heparin delivery is critically dependent on the efficiency of the nebuliser, and the deposition patterns produced by that device suggests it can deliver effective quantities of heparin directly to the areas of the lung where the disordered clotting is seen.

Mechanically ventilated patients

A recent study completed with 256 mechanically ventilated patients with or at risk of developing ARDS showed that nebulised heparin delivered by the Aerogen Solo device,reduced the development of ARDS and increased the number of surviving patients discharged home at day 60.

Dr Ronan MacLoughlin, senior science manager at Aerogen, said: “Not all nebuliser technologies are created equal, and here we are looking forward to bringing the inherent safety and performance advantages of Aerogen’s devices to bear in this important program.

"With the current focus on new and repurposed therapies for ARDS and Covid ARDS, it has never been more important to ensure that these therapies are screened effectively whilst ensuring that they are challenged robustly.

“In this project, we are looking at repurposing an existing drug with proven potential, but ensuring that enough is delivered to the patient, all while keeping the clinical team safe.

"Aerogen’s closed circuit nebulisers do not require circuit breaks during mechanical ventilation, and have been shown to deliver the highest levels of therapies to the ventilated patient’s lung and our aim is to ensure that this combination of drug and device provide maximum benefit, under the most critical conditions.

Highest burden respiratory diseases

“Building on long-standing collaborations with both the team in CURAM, and Prof Laffey, we look forward to advancing the state of the art in what have become some of the highest burden respiratory diseases, and provide a roadmap for future programmes looking to optimise and exploit the advantages of aerosol-mediated drug delivery to the lung, with a focus on the critical care setting.”

This is the third collaboration between CÚRAM and Aerogen. Earlier collaborations focusing on understanding the fluid mechanics of droplets and exploring enhancing the delivery of existing small molecule therapeutics worth more than €1 million have resulted in a significant number of co-publications with Aerogen that have being highly cited.

CÚRAM researchers on these collaborations have gained relevant industry training, improved scientific and technical skills and have gone on to secure roles in industry.

For more information about the research project contact Claire Riordan, public engagement manager, CÚRAM at claire.riordan@nuigalway.ie or Ciara Power, global customer marketing manager, Aerogen at cpower@aerogen.com.