CHÉOS researcher Dr. Joel Singer is part of an international team that recently received federal funding to help combat the COVID-19 pandemic.
Dr. Singer is the Program Head of Clinical Trials at CHÉOS, and has joined a team of researchers who received a $255,970 grant in the Canadian Institutes of Health Research (CIHR) Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding competition.
The team will investigate whether a certain class of blood pressure drugs can decrease the severity of COVID-19 infection. Within days of receiving the grant, the team had already recruited two patients from the intensive care unit (ICU) at St. Paul’s.
“I think that anyone who does clinical research will tell you that this is absolutely unheard of,” says Dr. Singer, who is also a UBC Professor in the School of Population and Public Health and the head of the data and methodology program at the CIHR Canadian HIV Trials Network (CTN). “One of the things that I quickly learned is that the usual ways of conducting research had to change in an emergent situation, and I am relieved that the various bodies that are involved in regulating projects are prioritizing this in the manner which it demands.”
The federal grant results were announced in early March as part of Canada’s efforts to learn more about this novel coronavirus and to develop tools and resources to combat it. The government invested $27 million to support 47 research teams from across Canada that will focus on accelerating the development, testing, and implementation of measures to deal with the COVID-19 outbreak.
Could ARBs be the golden ticket?
Dr. Singer and other researchers from across Canada will focus on angiotensin II type 1 receptor blockers (ARBs) – a class of drug commonly prescribed for high blood pressure, heart failure and diabetes. ARBs have been shown to prevent lung injury from influenza. The research team is proposing the drug could also work on COVID-19 since influenza and coronavirus bind to the same cell receptor in the lungs.
“ARBs are promising based on studies in models of influenza showing that ARBs decreased the numbers of virus in the lung (“viral load”) and decreased the severity of the influenza-induced pneumonia” explains Dr. Russell, the principal investigator of the study.
The researchers believe ARBs could decrease the severity and mortality of hospitalized COVID-19 infected adults. Decreased severity would mean less need for ventilation, vasopressors (drugs to raise low blood pressure), extracorporeal membrane oxygenation (machines to add oxygen to the blood if oxygen levels are critically low) or dialysis.
The study will evaluate safety and effectiveness of ARBs in COVID-19 in 497 hospitalized adult patients across more than 40 sites in Canada who are or are not already on ARBs. If this study is successful, ARBs – which are inexpensive and clinically available – could potentially be used globally to limit complications and death due to COVID-19.
New pathologies, new research, new techniques
Dr. Singer is also hoping that emerging research techniques, namely adaptive trial design, will be employed in the study of ARBs should they proceed to the randomized trial phase. “An adaptive trial is a trial where there are multiple treatment arms. With regular monitoring of outcomes, we can drop those treatments unlikely to come out the winner, and add new candidate therapies as they become available” he explains.
Adaptive research allows for continuous innovations as further information becomes available, a research technique well suited for COVID-19 considering the rapidly changing reality of the epidemic. The WHO is currently organizing an international adaptive trial, the Solidarity Trial, which has four experimental arms. Should data supporting the testing of ARBs be sufficiently strong, an ARBs arm could be added to this ongoing trial or other similar adaptive trials, which are likely to start in the coming months. Time is of the essence and, with sufficient international cooperation, this could be the ideal way to narrow down effective candidates.
In addition to their primary goal – to see if ARBs limit COVID-19 complications and death – the investigators have a number of other aims. They will also test whether levels of certain biomarkers in the blood predict a better response to ARBs, they will see if people who are already taking ARBs are less likely to contract severe COVID-19, and they will determine whether ARBs reduce the risk of cardiac arrest among patients infected with COVID-19 who also live with a comorbidity like diabetes or hypertension.