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

NCT04760821 | Unknown Phase 2

• 1 other identifier: SDC5100/20/129
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Respiratory Distress Syndrome; Covid19; Myocardial Injury

Keywords

Acute Respiratory Distress Syndrome; Coronavirus; Myocardial Injury; Troponin; Trimetazidine

Outcome Measures

Primary Outcomes (1)

• High-sensitivity cardiac troponin

  Concentration levels of plasma high-sensitivity cardiac troponin

  From enrollment until at least ten days (moderate cases) or twenty days (severe cases) after the beginning of symptoms AND 24 hours without fever AND with improvement in symptoms.

Secondary Outcomes (5)

• All-cause mortality assessed at 30 days following randomization

  From the first 30 days after randomization

• Admission in ICU assessed at 30 days following randomization

  From the first 30 days after randomization

• Mechanical respiratory support assessed at 30 days following randomization

  From the first 30 days after randomization

• ICU-free days assessed at 30 days following randomization

  From the first 30 days after randomization

• Hospital-free days assessed at 30 days following randomization

  From the first 30 days after randomization

Study Arms (2)

Usual Care

NO INTERVENTION

Patients ascribed to the Usual Care group will receive the standard of care for the management of patients admitted with moderate to severe acute respiratory distress syndrome due to SARS-CoV2. Usual Care means the clinical protocol approved by the enrolling center.

Trimetazidine

EXPERIMENTAL

Patients ascribed to the Usual Care group will receive the standard of care for the management of patients admitted with moderate to severe acute respiratory distress syndrome due to SARS-CoV2 plus trimetazidine.Usual Care means the clinical protocol approved by the enrolling center.

Drug: Trimetazidine

Interventions

Trimetazidine DRUG

Trimetazidine 35mg bid in patients with GFR above 60mL/min. Trimetazidine 35mg od in patients with GFR between 30 and 60mL/min.

Trimetazidine

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of moderate to severe acute respiratory syndrome due to SARS-CoV2 defined as:
• 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:
• Polymerase chain reaction assay (+) for SARS-CoV2
• Serology (+) for SARS-CoV2
• SARS-CoV2 antigen diagnostic tests (+)
• 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
• Signature of the Informed Consent Form

You may not qualify if:

• Chronic renal dysfunction stage 4 (GFR \<30mL / min / 1.73m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
• Patient on renal replacement therapy by dialysis
• Pregnant and lactating women
• Previous use of trimetazidine less than two weeks before hospital admission
• Any clinical condition at the investigator´s discretion likely to be associated with elevation of baseline hs-troponin \>99th percentile

Sponsors & Collaborators

• Ministry of Health, Brazil: lead
• InCor Heart Institute: collaborator

Study Sites (1)

Heart Institute (InCor-HCFMUSP)

São Paulo, São Paulo, 05403-000, Brazil

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome; COVID-19; Coronavirus Infections

Interventions

Trimetazidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Luis Henrique Wolff Gowdak, MD, PhD

  InCor (HC-FMUSP)

  STUDY CHAIR

• Felipe Gallego Lima, MD

  InCor (HC-FMUSP)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luis Henrique Wolff Gowdak, MD, PhD

CONTACT

+55-11-2661-5000; luis.gowdak@gmail.com

Felipe Gallego Lima, MD

CONTACT

+55-11-2661-5000; felipeglima@yahoo.com.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Scientist

Model Details: Patients admitted for moderate to severe acute respiratory distress syndrome caused by the SARS-CoV2 will be randomized to usual care or usual care + trimetazidine.

Study Record Dates

• First Submitted: February 17, 2021
• First Posted: February 18, 2021
• Study Start: December 10, 2020
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)