Prevention of Acute Myocardial Injury by Trimetazidine in Patients Hospitalized for COVID-19

• Status: Recruiting
• Trial end date: 2021-04-30
• Target enrollment: 0
• Participant gender: All

Summary

Acute myocardial injury has been a finding of variable frequency among patients diagnosed with COVID-19. It is now recognized that cTnI levels are strongly associated with increased mortality. The mechanisms underlying the myocardial injury remain unknown, and it is not clear whether they reflect local/systemic inflammatory process and/or cellular ischemia.

Both myocardial ischemia and ventricular dysfunction result in dramatic changes in mitochondrial oxidative metabolism. These changes involve an increase in the rate of cytoplasmic anaerobic glycolysis to compensate for the decrease in mitochondrial adenosine triphosphate (ATP) production. The rest of the mitochondrial oxidative metabolism originates mainly from the β-oxidation of free fatty acids, which occurs at the expense of glucose oxidation.

Trimetazidine is a competitive inhibitor of the enzyme 3-ketoacyl coenzyme A (CoA) long-chain thiolase (3-KAT), the last enzyme involved in the oxidation of fatty acids. Stimulation of glucose oxidation by trimetazidine results in a better coupling between glycolysis and glucose oxidation, with a consequent decrease in lactate production and intracellular acidosis, present in situations of myocardial ischemia or heart failure.

Thus, the PREMIER-COVID-19 study was designed to test the hypothesis that the use of trimetazidine associated with usual therapy in patients admitted with a diagnosis of moderate to severe acute respiratory syndrome by SARS-CoV2 infection reduces the extent of acute myocardial injury assessed by the peak release of ultra-sensitive troponin compared to usual therapy.

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

Details

• Lead Sponsor: Ministry of Health, Brazil
• Collaborator: InCor Heart Institute
• Treatments: Trimetazidine

Criteria

A. Inclusion Criteria:

1. Clinical diagnosis of moderate to severe acute respiratory syndrome due to SARS-CoV2 defined as:

1.1. Tachypnea: > 24 breaths per minute 1.2. Hypoxemia: arterial oxygen saturation <94% in room air by pulse oximetry 1.3. Presumptive (or confirmed) diagnosis of SARS-Cov2 infection by at least one of the following criteria:

1. Polymerase chain reaction assay (+) for SARS-CoV2

2. Serology (+) for SARS-CoV2

3. SARS-CoV2 antigen diagnostic tests (+)

4. Chest CT with findings suggestive of the diagnosis of COVID-19 in the presence of medical history or clinical signs compatible with the diagnosis of COVID-19

2. Signature of the Informed Consent Form

B. Exclusion Criteria:

1. Chronic renal dysfunction stage 4 (GFR <30mL / min / 1.73m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

2. Patient on renal replacement therapy by dialysis

3. Pregnant and lactating women

4. Previous use of trimetazidine less than two weeks before hospital admission

5. Any clinical condition at the investigator´s discretion likely to be associated with elevation of baseline hs-troponin >99th percentile