Grant: Operating Grant: COVID-19 Rapid Research Funding Opportunity - Therapeutics

As the COVID-19 pandemic continues to spread globally, the World Health Organization (WHO) and others are actively conducting clinical trials for anti-virals to combat this disease. However, many of the severe complications of COVID-19 are caused by the host's response to viral infection. We have a unique opportunity to complement these ongoing studies with our clinical trial to test how modulating the host response can improve outcomes for hospitalized COVID-19 patients. We plan to re-purpose a class of drugs called angiotensin II receptor blockers (ARBs), which are normally used to treat high blood pressure and other cardiovascular diseases. ARBs have been shown to prevent lung injury in influenza (the flu), which is caused by a virus that uses similar mechanisms as SARS-CoV-2 (the virus that causes COVID-19) to enter human cells. We will recruit 1,732 patients from multiple sites throughout Canada and randomize them to be treated with either Losartan (a commonly prescribed ARB with an excellent safety profile), or to continue under usual care. We will evaluate whether patients who receive Losartan have better outcomes, such as decreased mortality and organ dysfunction, than those who receive usual care. At the same time, we will collect blood samples from these patients to determine whether there are certain molecular "markers" that can predict mortality and their response to Losartan. This study will provide guidance on whether Losartan can be used to limit organ dysfunction and mortality in hospitalized COVID-19 patients, ultimately resulting in better care and outcomes for patients during this global pandemic.