Semaglutide to Reduce Myocardial Injury in PATIents With COVID-19 Randomized Controlled Trial

6.1 Background

The current COVID-19 pandemic is rapidly spreading with a global total of ~35 million cases, with close to 170,000 cases and over 9,500 deaths in Canada alone (as of 10/05/2020). Most affected patients have mild or even no symptoms, however, those requiring hospitalization have a more severe presentation including pneumonia, acute respiratory distress syndrome (ARDS), cardiovascular collapse and death. There is mounting evidence that myocardial injury, occurring in 8-28% of hospitalized patients, has a major impact on mortality. In a study from Wuhan in China, mortality was 59.6% in COVID-19 patients with an elevated troponin and only 8.9% in those with a normal troponin level. ARDS was also more common in troponin-positive patients. The pathophysiology of myocardial injury following COVID-19 infection is not well understood, but may include viral myocarditis, cardiomyocyte injury from systemic cytokine storm, reductions in myocardial blood flow from micro- and macro-vascular thromboses, and severe hypoxemia in the setting of pre-existing cardiovascular disease (CVD).1 Higher rates of adverse outcomes with COVID-19 have also been noted in patients with hypertension and diabetes. Based on these data, approaches to prevent or reduce the vascular consequences of COVID-19 may be beneficial and should be prioritized for rapid evaluation in controlled clinical trials.

Currently there is a paucity of approved therapies for COVID-19 infection. Current interventions are either supportive in nature or experimental anti-viral, anti-inflammatory, or anti-coagulant in nature. Only dexamethasone has recently been shown to reduce mortality. To date, there is no proposed treatment directly addressing the mechanisms of increased cardiovascular risk in this deadly disease. The investigators have strong rationale and world-leading expertise in this area. This is a prospective, randomized, controlled, open-label, blinded-evaluation, exploratory (vanguard) study in hospitalized symptomatic COVID-19 patients age with any two of the following high-risk features: age >60 years, obesity (BMI> 30), diabetes (by history - with or without medical treatment), hypertension (on any treatment), cardiovascular disease (by history), chronic kidney disease (eGFR <60) or elevated biomarkers on admission to hospital (troponin, d-dimer). Eligible and consented patients will be randomized to one of the following two treatment regimens in a 1:1 ratio: (1) semaglutide 0.25 mg s.c. immediately after randomization at baseline, then 0.5 mg s.c. at day 7, day 14, and day 21. The end of treatment period and primary outcome assessments will occur on day 28. Final secondary clinical outcome assessment will be at 180 days.

With the results of this study the investigators aim to identify an effective treatment that will reduce morbidity and mortality of patients with symptomatic COVID-19 infection, which would in turn reduce the burden on the healthcare system by decreasing the need for intensive care.

Objectives: The main objective of this research is to determine if once weekly treatment with the GLP-1 agonist semaglutide for 4 doses will reduce cardiac as well as non-cardiac complications of COVID-19 infection.