Semaglutide to Reduce Myocardial Injury in PATIents With COVID-19

NCT04615871 | Unknown Phase 2 DMC

• 1 other identifier: UHNSEMPATICO1
• Study Type: interventional
• Target: 400
• Locations: 4 countries
• Sites: 10

Brief 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 participants will 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 1 week (7-days) post randomization. Other major secondary outcome measure: A composite of

1. 1.Death from any cause, mechanical ventilation or vasopressor or ECLS support at 28 days
2. 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.

Conditions

Covid19; Myocardial Injury

Keywords

Covid-19; myocardial injury; GLP-1 agonist; semaglutide

Outcome Measures

Primary Outcomes (1)

• Composite of death or mechanical ventilation

  All cause death or invasive or non-invasive mechanical ventilation

  28 days after randomization

Secondary Outcomes (5)

• cardiac troponin level

  7±2 days after randomization

• cardiac troponin level

  14±2 days after randomization

• ECG

  Day 7±2 and Day 14±2

• 28-day organ support-free days

  28 days

• A composite of death or intensification of medical therapy

  180 days

Study Arms (2)

semaglutide

EXPERIMENTAL

Eligible subjects randomized to this arm will receive semaglutide 0.25 mg s.c. after randomization (Day 0), then semaglutide 0.5 mg s.c. on Day 7, Day 14 and Day 21 in addition to standard of care.

Drug: semaglutide

control

NO INTERVENTION

Eligible subjects randomized to the control arm will receive no active treatment, only standard of care.

Interventions

semaglutide DRUG

semaglutide 0.25 mg s.c. on Day 0 after randomization, then semaglutide 0.5 mg s.c. on Day 7, Day 14 and Day 21

Also known as: Ozempic

semaglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 need for any O2 therapy

You may not qualify if:

• 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
• Breastfeeding, if they intend to continue breastfeeding
• 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 with high flow nasal cannula at FiO2 \>50% or already on mechanical ventilation
• 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 from patient or Substitute Decision Maker (SDM)

Sponsors & Collaborators

• Vladimír Džavík: lead
• Unity Health Toronto: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• University of Toronto: collaborator

Study Sites (10)

Instituto Prevent Senior

São Paulo, Brazil

NOT YET RECRUITING

State University of Campinas

São Paulo, Brazil

NOT YET RECRUITING

Trillium Health Partners

Mississauga, Ontario, Canada

NOT YET RECRUITING

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

University Health Network - Peter Munk Cardiac Centre

Toronto, Ontario, Canada

NOT YET RECRUITING

McGill University Health Centre

Montreal, Quebec, Canada

RECRUITING

Hospital de Infectologia

Mexico City, Mexico

NOT YET RECRUITING

Hospital General Regional

Mexico City, Mexico

NOT YET RECRUITING

Hospital Regional 2

Querétaro, Mexico

NOT YET RECRUITING

Sandwell and West Birmingham NHS Trust

Birmingham, B18 7QH, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

COVID-19

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Vladimir Dzavik, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Mansoor Husain, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sorcha Mulligan

CONTACT

416-360-4000; sorcha.mulligan@unityhealth.to

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Randomized open-label blinded evaluation trial. There will be an independent events adjudication committee
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Patients will be randomized to receive active treatment - s.c. semaglutide for 4 weekly doses in addition to standard of care or control - standard of care only

Study Record Dates

• First Submitted: October 29, 2020
• First Posted: November 4, 2020
• Study Start: September 10, 2021
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: February 8, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (2); ME (3); CA (4); GB (1)