Myocardial Protection in Patients With Post-acute Inflammatory Cardiac Involvement Due to COVID-19 — MYOFLAME-19  

Left Ventricular Dysfunction Clinical Trial

Official title: Randomised Placebo Controlled Clinical Trial of Efficacy of MYOcardial Protection in Patients With Postacute inFLAMmatory Cardiac involvEment Due to COVID-19

Status Recruiting

Clinical Trial Summary

Long COVID or Postacute sequelae of COVID-19 infection (PASC) are increasingly recognised complications, defined by lingering symptoms, not present prior to the infection, typically persisting for more than 4 weeks. Cardiac symptoms due to post-acute inflammatory cardiac involvement affect a broad segment of people, who were previously well and may have had only mild acute illness (PASC-cardiovascular syndrome, PASC-CVS). Symptoms may be contiguous with the acute illness, however, more commonly they occur after a delay. Symptoms related to the cardiovascular system include exertional dyspnoea, exercise intolerance chest tightness, pulling or burning chest pain, and palpitations (POTS, exertional tachycardia).

Pathophysiologically, Long COVID relates to small vessel disease (endothelial dysfunction) vascular dysfunction and consequent tissue organ hypoperfusion due to ongoing immune dysregulation. Active organs with high oxygen dependency are most affected (heart, brain, kidneys, muscles, etc.). Thus, cardiac symptoms are often accompanied by manifestations of other organ systems, including fatigue, brain fog, kidney problems, myalgias, skin and joint manifestations, etc, now commonly referred to as the Long COVID or PASC syndrome.

Phenotypically, PostCOVID Heart involvement is characterised by chronic perivascular and myopericardial inflammation. We and others have shown changes using sensitive cardiac MRI imaging that relate to cardiac symptoms (Puntmann et al, Nature Medicine 2022; Puntmann et al, JAMA Cardiol 2020; Summary of studies included in 2022 ACC PostCOVID Expert Consensus Taskforce Development Statement, JACC 2022, references below).

Early intervention with immunosuppression and antiremodelling therapy may reduce symptoms and development of myocardial impairment, by minimising the disease activity and inducing disease remission. Low-dose maintenance therapy may help to maintain the disease activity at the lowest possible level. The benefits of early initiations of antiremodelling therapy to reduce symptoms of exercise intolerance are well recognised, but not commonly employed outside the classical cardiology contexts, such as heart failure or hypertension. As most patients with inflammatory heart disease only have mild or no structural abnormalities, they are left untreated (standard of care).

The aim of this study is to examine the efficacy of a combined immunosuppressive / antiremodelling therapy in patients with PASC symptoms and inflammatory cardiac involvement determined by CMR, to reduce the symptoms and inflammatory myocardial injury and thereby stop the progression to reduced LVEF, HF and death.

References:

https://www.nature.com/articles/s41591-022-02000-0

https://jamanetwork.com/journals/jamacardiology/fullarticle/2768916

https://www.jacc.org/doi/abs/10.1016/j.jacc.2022.02.003

Clinical Trial Description

Patients with documented COVID-19 infection, experiencing new cardiac symptoms in the aftermath of COVID-19 infection, fulfilling predefined CMR criteria for PostCOVID myocardial involvement and no previously known or demonstrable cardiovascular disease will be randomised to 16-week treatment with Losartan/Prednisolon or placebo. All imaging is conducted with fidelity to standardised imaging protocol. All images are analysed in a dedicated core-lab to confirm eligibility for inclusion. Investigators and participants remain blinded to group allocation and imaging results.

The primary outcome is a change in LVEF from the baseline to 16 weeks measured by MRI.

Secondary outcomes include changes in clinical symptom scores, imaging parameters, CPET (VO2max), as well as outcomes after 1 and 5 years time. ;

Related Conditions & MeSH terms

• COVID-19
• Exercise Intolerance
• Inflammation
• Left Ventricular Dysfunction
• Microvascular Angina
• Remodeling, Left Ventricle
• Vascular Inflammation
• Vascular Remodeling
• Ventricular Dysfunction
• Ventricular Dysfunction, Left
• Ventricular Remodeling

• NCT number: NCT05619653
• Study type: Interventional
• Source: Johann Wolfgang Goethe University Hospital
• Contact: Valentina Puntmann, MD, PhD
• Phone: ?+4969630189441?
• Email: CVI-Myoflame@kgu.de
• Status: Recruiting
• Phase: Phase 3
• Start date: December 12, 2022
• Completion date: December 31, 2028