A study to assess the efficacy of a cardiac drug and a anti-inflammatory drug in patients with post-acute inflammatory heart disease due to COVID-19

Phase 1

• Conditions: Inflammatory cardiovascular involvement due to COVID-19, defined by Cardiovascular magnetic resonance imaging; MedDRA version: 23.0Level: PTClassification code 10084268Term: COVID-19System Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0Level: LLTClassification code 10007650Term: Cardiovascular disorder NOSSystem Organ Class: 10007541 - Cardiac disorders; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2022-001682-12-AT
• Lead Sponsor: Goethe University Frankfurt

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-22
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

• Participants = 18 years
• Participants with documented recent COVID19 infection (> 4 weeks)
• Post-acute sequelae of SARS-CoV-2 infection (PASC) Syndrome, defined by persistence or new symptoms, not present prior to the infection.
• Cardiovascular magnetic resonance imaging (CMR) evidence of inflammatory cardiac involvement at baseline (BL) by any of the following criteria:
o Increased native T1= 1130 ms at 3.0 Tesla (or 1030 ms at 1.5 Tesla) and/or;
o Increased native T2 =39.5 ms at 3.0 Tesla (or 49.5 at 1.5 Tesla) and/or
o present non-ischaemic myopericardial Late gadolinium enhancement (LGE) and/or;
o Left ventricular ejection fraction (LVEF) =45 - =50%.
• Willingness to comply with the study procedures and study protocol.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140

Exclusion Criteria

• Severe course of acute COVID illness requiring hospitalisation
• Known allergy to or intolerance of the study medications
• Symptomatic hypotension (systolic blood pressure less than 90 mm Hg), not reversible with oral hydration
• Any previous or current use of ACE inhibitors, AR Blockers
• Any previous oral prednisolone, or any other immunosuppressive or biological treatment (within 10 weeks)
• History or CMR evidence of preexisting heart disease, including:
a. Known cardiac impairment with LVEF =44%
b. Congestive heart failure (NYHA III-IV)
c. Active heart failure treatment
d. Established ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease
e. Persistent or permanent atrial fibrillation or significant heart rhythm abnormalities.
f. Congenital or clinically relevant valvular heart disease (moderate or severe)
g. Specific cardiomyopathy (hypertrophic, hypertensive heart disease, amyloidosis, previous myocarditis, non-ischaemic dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, non-compaction cardiomyopathy, etc).
h. Known significant concomitant diseases that are likely to interfere with the evaluation of the participant's safety and of the study outcome (e.g. diabetes, lung or hepatic disease, epilepsy, psychiatric disorders, renal disease with a current estimated GFR <30 mL/min/1.73 m² using MDRD formula, chronic systemic infection or immunocompromise)
i. Exceeding scanner bore and table-holding capacity: Weight >125 kg, BMI > 35 kg/m2
• Contraindications to contrast-enhanced CMR imaging, e.g.
a. MR-unsafe implantable device
b. known allergy to gadolinium-based contrast agent (GBCA)
• For female participants:
a. Pregnant or lactating women
b. Women of childbearing potential not willing to use effective contraception (as defined in18.2.13)
• Known alcohol, drug, or chemical abuse
• Participants currently participating in an investigational study or for whom participation is planned.
• Unable to provide written informed consent

Patients with CMR evidence of structural heart disease or incidental heart rhythm abnormalities will be advised to see their own doctor for further investigations.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to determine the efficacy of a combined immunosuppressive and antiremodelling therapy in COVID-19 related inflammatory cardiovascular involvement by CMR to reduce inflammatory myocardial injury compared to placebo.<br><br>The primary safety objective is to demonstrate that a combined immunosuppressive and antiremodelling therapy in proposed doses in this patient population is safe.;Secondary Objective: The secondary objectives are to determine the efficacy of a combined immunosuppressive and antiremodelling therapy in COVID-19 related inflammatory cardiovascular involvement by CMR to reduce inflammatory myocardial injury compared to placebo by improvement in other clinical parameters.;Primary end point(s): The primary endpoint of this study is absolute LVEF change to baseline at W16, measured by CMR, compared between the verum and placebo group by absolute treatment difference;Timepoint(s) of evaluation of this end point: Baseline and week 16