NCT04760821: PREMIER

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

Status unknown Phase 2 Last updated 21 February 2021

What this trial tests

Phase 2 trial testing Trimetazidine in Acute Respiratory Distress Syndrome in 80 participants. Status unknown.

Timeline

10 December 2020

Primary endpoint
30 April 2021

30 April 2021

Quick facts

Lead sponsor	Ministry of Health, Brazil
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	80
Start date	10 December 2020
Primary completion	30 April 2021
Estimated completion	30 April 2021
Sites	1 location across Brazil

Drugs / interventions tested

• Trimetazidine (TRIMETAZIDINE) — full drug profile →

Conditions studied

• Acute Respiratory Distress Syndrome — all drugs for Acute Respiratory Distress Syndrome →
• Covid19 — all drugs for Covid19 →
• Myocardial Injury — all drugs for Myocardial Injury →

Sponsor

Ministry of Health, Brazil

Who can join

18 and older, any sex, with Acute Respiratory Distress Syndrome or Covid19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Acute Respiratory Distress Syndrome and COVID-19: A Literature Review.
   Hussain M, Khurram Syed S, Fatima M, Shaukat S, et al · · 2021 · cited 38× · PMID 34992415 · DOI 10.2147/jir.s334043
2. Role of mitochondria in physiological activities, diseases, and therapy.
   Wang L, Zhou X, Lu T. · · 2025 · cited 23× · PMID 40536597 · DOI 10.1186/s43556-025-00284-5