Clinical Trial for COVID-19
RAAS COVID Trial is a new study that is underway at the McGill University Health Center in Montreal. The aim of the investigation is to understand the effect of a commonly prescribed medication on COVID-19 outcomes in hospitalized patients.
Since 2019, SARS-CoV-2 has claimed the lives of more than 2 million individuals worldwide. This novel coronavirus has halted societal operations across multiple countries and challenged the healthcare system relentlessly. In the face of this growing global issue, McGill cardiologists and researchers have designed a sophisticated trial with the hope of guiding better management in patients with active infection.
At the current moment, it is estimated that among patients admitted to the hospital for COVID-19 infection, 27% will require intensive care unit monitoring, 25% will require mechanical ventilation, and 28% will die from the infection¹. Recent studies identified that patients with pre-existing hypertension, heart failure or previous heart attack have the highest mortality among those infected with the virus. The exact mechanism predisposing these individuals to higher risk of death is not clear.
The group of researchers and cardiologists at McGill lead by the principle investigator Dr. Abhinav Sharma have taken initiative to evaluate the effect of RAAS inhibitors, a commonly prescribed treatment in patients with heart disease. This class of medication has been studied extensively among COVID-19 patients, though most studies have been observational. In other words, there has been no definite evaluation of the impact of this medication among those hospitalized with the infection.
“The group of researchers and cardiologists at McGill lead by the principle investigator Dr. Abhinav Sharma have taken initiative to evaluate the effect of RAAS inhibitors”
Simply, this class of medication stands for renin-angiotensin-aldosterone system inhibitors. They are frequently prescribed to individuals with various forms of heart disease as they have been shown in multiple studies to reduce mortality and adverse cardiovascular outcomes.
It has been postulated that RAAS inhibitors increase levels of an enzyme called ACE2. It is believed that SARS-CoV-2 utilizes this enzyme to gain entry into cells; thereby exacerbating active infections.
If these drugs could exacerbate active infections, why do we continue to use them?
In fact, most of the data about RAAS inhibitors increasing ACE2 levels come from animal studies. In the world of research, responses in animal studies rarely completely correlate with those in human subjects. Additionally, a study by Zhang et al. as well as a large cohort study in Britain have shown that this class of medication has improved outcome and reduced rates of COVID infections, respectively. In this sense, most guidelines have said that more studies are required to make recommendations about the safety of using RAAS inhibitors in patients with active COVID-19 infection. A more recent investigation entitled BRACE-CORONA trial showed that continuing RAAS inhibitors was safe in hospitalized patients with mild to moderate COVID-19 infection. One of the aims of our current initiative is to provide further details on this topic.
Given the absence of extensive randomized controlled trials (RCT) and conflicting evidence between animal studies and observational data, there is sufficient reason for a trial to be conducted on this subject. The current state of affairs is termed “clinical equipoise”, i.e. it is unclear whether continuing RAAS inhibitors in patients with active SARS-CoV-2 infection improves or worsens outcomes.
The path to answers: designing RAAS COVID Trial
In order to develop high-quality evidence that will help clinicians better manage the burden of this pandemic, the methodology behind this clinical study must be nothing short of perfect. In the next paragraphs, a walk-through will be provided to better understand the conclusions this investigation will eventually report. Of note, the hypothesis of the research group is that continuing RAAS inhibitors is superior to discontinuing the medication in terms of global rank score. This will be clarified with explanations below.
A total of 40 patients with active COVID-19 diagnosed within 96 hours and currently hospitalized at either the Royal Victoria Hospital, Montreal General Hospital or Jewish General Hospital will be enrolled. Among the many inclusion and exclusion criteria detailed further in our publication, individuals must have been on a RAAS inhibitor for at least 1 month prior to admission.
The enrolled individuals will be randomized to one of two groups using a random number generator. One of the groups will have their RAAS inhibitor medication discontinued for a duration of 7 days with alternative anti-hypertensive therapy provided. The other group will not have that class of medication discontinued. The general principle would be to follow over a period of 30 days in order to determine differences in outcomes between these two groups.
In order to evaluate differences between both groups appropriately, a global rank score was designed to weigh the importance of various outcomes. The global rank score works by assigning each patient a total number of points based on outcomes such as death, need for mechanical ventilation, increase in inflammatory markers in the blood, etc. For example, a patient that is transferred to the ICU for mechanical ventilation would get 6 points in addition to all other points assigned for adverse events present on the global rank score. A higher score on this scale indicates a poorer hospitalization course (i.e. a less stable patient). The average score in both groups will be calculated and compared in order to detect any differences between the treatment groups.
To learn more about the results of our trial, follow us on Twitter. More detailed information about the RAAS COVID Trial will be available upon publication.
CV-Dreams Lab is a research initiative at the MUHC lead by the principle investigator and cardiologist Dr. Abhinav Sharma.
Researchers involved in the trial: Dr. Aflaki, Alexandria Flannery, Dr. João Pedro Ferreira, Dr. Matthew Pellan Cheng, Dr. Nadine Kronfli, Dr. Ariane Marelli, Dr. Faiez Zannad, Dr. James brophy, Dr. Jonathan Afilalo, Dr. Thao Huynh, Dr. Nadia Giannetti, Dr. Amal Bessissow, Justin A Ezekowitz, Dr. Renato D Lopes, Dr. Andrew P Ambrosy, Morgan Craig
Medium article writer: Elie Ganni
