NOx Technology: A "solution" for prevention of ventilator associated pneumonia in critically ill patients.

We have developed, and patent protected, a novel, non-enzymatic, system for exogenous generation and local delivery of nitric oxide (NO) and higher oxides of nitrogen (NOx).

The system is prepared via a mixture of sodium nitrite and ascorbic, or citric, acid, which generates large amounts of exogenous NOx via the chemical reactions of acidified nitrite. The reaction mixture can be tailored for suitability to specific applications.

Our proposal is to deliver the solution in a liquid form to the stomach and oral cavity of mechanically ventilated patients. We believe use of this technology will significantly reduce the incidence of ventilator associated pneumonia (VAP) in these patients.

There is now persuasive evidence that the oxides of nitrogen (NOx) play a key role in the maintenance of host defence against various microbial pathogens. In health, NOx is present in high concentrations in the stomach where it plays an important role in maintaining intragastric sterility and preventing gastrointestinal infections. Mechanically ventilated patients are usually sedated, they produce little or no saliva and their swallowing reflex is inhibited or abolished. VAP is caused by aspiration of infected secretions from the aerodigestive tract.

Our own pilot studies have confirmed that during critical illness, production of oxides of nitrogen, which play key roles in host defense is markedly reduced. This predisposes to colonization of the stomach and oral cavity by pathogenic bacteria and hence the subsequent development of VAP. Our NO-generating solution is designed to restore normal physiological activity of NOx by nasogastric and oral administration.

Ventilator associated pneumonia (VAP) is a lung infection occurring in patients who have been mechanically ventilated for more than 48 hours [1]. The reported incidence of VAP varies from around 10% to more than 30%. It is estimated that over 60,000 patients are mechanically ventilated in UK intensive care units (ICUs) annually, with an average stay of five days and a cost of around £500M per annum (approx 1-2 % of the total NHS budget). VAP is the most prevalent infection in European ICUs, accounting for almost half of all ICU acquired infections.

Our aim is to reduce significantly the incidence of VAP and the associated prolonged length of stay, morbidity, mortality and treatment costs. Pilot clinical studies with a prototype product will pave the way for future Phase III studies, dependent on confirmation of safety, efficacy and development of an easy-to-use delivery system.

We have developed, a novel, non-enzymatic, system for exogenous generation and local delivery of nitric oxide (NO) and higher oxides of nitrogen (NOx).
Prepared via an admixture of sodium nitrite and ascorbic, or citric, acid, the system generates large amounts of exogenous NOx via the chemical reactions of acidified nitrite. We propose to deliver the solution in liquid form to the stomach and oral cavity of mechanically ventilated patients.
There is now persuasive evidence that the oxides of nitrogen (NOx) play a key role in the maintenance of host defence against various microbial pathogens. In health, NOx is present in high concentrations in the stomach where it plays an important role in maintaining intragastric sterility and preventing gastrointestinal infections.
Ventilator associated pneumonia (VAP) is a nosocomial infection occurring in patients who have been mechanically ventilated for more than 48 hours [1]. These patients are usually sedated, they produce little or no saliva and their swallowing reflex is inhibited or abolished. VAP is caused by aspiration of infected secretions from the aerodigestive tract.
Our own pilot studies have confirmed that during critical illness, production of oxides of nitrogen, which play key roles in host defense, is markedly reduced. This predisposes to colonization of the stomach and oral cavity by pathogenic bacteria and hence the subsequent development of VAP. Our NO-generating solution is designed to restore normal physiological activity of NOx by nasogastric and oral administration.
Our aim is to reduce significantly the incidence of VAP and the associated prolonged length of stay, morbidity, mortality and treatment costs. Phase I and II developmental clinical studies with a prototype product will pave the way for future Phase III studies, dependent on confirmation of efficacy and development of an easy-to-use delivery system.

The Pathway to Impact will be the completion of the design and manufacture of the product for clinical studies, progression from the exisitng prototype to commercial scale product manufacture - 2-3months: submission of CTA to regulatory authorities- 3months; phase 1 study - 4-6 months; Phase 2 study - 9months; randomised multicentre clinical studies -12-18months; regulatory approval after completion of clinical studies; market assessment - 2 months. Commercial partners to manufacture the NOx solution to clinical grade have been identified to make the product to be used in the clinical studies. In addition, product design work is being conducted for formulation and packaging of a commercial product ready for market once successful clinical studies have been completed.
The potential impact is huge. More than 60,000 patients are mechanically ventilated in UK intensive care units annually, with an average stay of five days and a cost of more than £500m. Up to a third of these patients develop pneumonia. The team envisage that their treatment will be administered to all patients in ICUs worldwide, being placed on a ventilator, to prevent development of pneumonia.