Semaglutide to Reduce Myocardial Injury in PATIents With COVID-19

• Status: Not yet recruiting
• Trial end date: 2022-03-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

Study Plan: The study design is prospective randomized open-label blinded-evaluation (PROBE). Eligible patients with symptomatic COVID-19 infection and an enhanced risk profile as described above, who have been admitted to hospital due to symptoms of COVID-19 infection but do not as yet require critical care will be approached to participate in this study. Provided there are no exclusion criteria and the participants agree by means of documented written informed consent, The participants the participantswill be randomized to receive s.c. semaglutide 0.25 mg s.c. or control immediately after randomization and then 0.5 mg s.c. at Day 7, Day 14 and Day 21. Blood will be drawn at Day 7±2 and Day 14±2 for the cardiac troponin biomarker and safety parameters. ECG will be obtained at Day 7±2 and Day 14±2. Primary outcome will be assessed on Day 28.

Primary outcome measure: A composite of (1) death from any cause or (2) mechanical ventilation (invasive or non-invasive) at 28 days.

Major secondary outcome measure:

(1) an elevation to >99th percentile URL upper reference limit (URL) in those with a baseline cardiac troponin level ≤99th percentile URL; or 3x elevation from baseline in those with a baseline cardiac troponin >99th percentile URL; measured at Day 7±2 days and Day 14±2 days post randomization.

Other major secondary outcome measure:

A composite of

1. Death from any cause, mechanical ventilation or vasopressor or ECLS support at 28 days

2. an elevation to >99th percentile URL in those with a normal baseline troponin level; or 3x elevation from baseline in those with a baseline troponin; measured at 1 and 2 weeks (7±2 and 14±2 days) post randomization.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vladimír Džavík
• Collaborators: Canadian Institutes of Health Research (CIHR); St. Michael's Hospital, Toronto; Unity Health Toronto; University of Toronto

Criteria

Inclusion Criteria:

Symptomatic* COVID-2 infection confirmed by a positive COVID-19 test requiring hospitalization [or equivalent health care setting] with any two of the following high-risk features:

• age ≥ 60 years

• obesity (BMI >30)

• diabetes mellitus

• hypertension (on treatment or recently diagnosed)h

• coronary artery, cerebrovascular or peripheral vascular disease∫

• chronic kidney disease (CKD) [eGFR <60 mL/min/1.73m2 using the CKD Epidemiology Collaboration equation

• admission troponin >99% of ULN

• admission d-dimer > 1µg/ml

• O2 saturation ≤93% e on room air or ≤95% on O2 therapy at 1-4 LPM

Exclusion Criteria:

• Age <18 years

• History of pancreatitis

• History of multiple endocrine neoplasia or medullary thyroid cancer

• Current use of a GLP-1 receptor agonist [use of a DPP-4 inhibitor is allowed]

• Positive beta-HCG (pregnancy test is mandated with baseline bloodwork for all female subjects ≤50 years of age

• Elevation of serum lipase, direct (conjugated) bilirubin, or alkaline phosphatase (ALP) more than 3X the upper limit of normal on baseline bloodwork

• history of decompensated heart failure with reduced ejection fraction (<35%) within 90 days, or known stable NYHA class IV heart failure prior to their COVID-19 illness

• imminent mechanical ventilation or death

• O2 therapy >4 LPM by nasal cannula or mask or already receiving non-invasive mechanical ventilation on enrolment

• Any marker of hemodynamic instability at baseline defined as persistent SBP <90 mmHg after rehydration, or > 220 mmHg after receiving routine antihypertensive therapy, or HR <50 bpm or > 140 bpm after rehydration.

• inability to provide informed consent