Evaluation of Trimetazidine Dihydrochloride on Endothelial Function and Prognostic Biomarkers in Heart Failure with Preserved Ejection Fraction
- Trial ID
- 2023-506138-65-00
- Protocol
- NBK531/2/2022
- Sponsor
- Medical University Of Gdansk
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is the **assessment of time to hospitalization or death from any cause** in patients with heart failure with preserved ejection fraction. This is clinically relevant as it provides insights into the overall prognosis and potential impact of treatment on patient outcomes in this population.
Secondary objectives include:
- Assessment of time to hospitalization for cardiovascular reasons and for any reason.
- Assessment of time to death from cardiovascular causes and from any cause.
- Evaluation of quality of life using the EQ-5D test.
- Assessment of symptoms of heart failure and angina.
- Evaluation of endothelial function, inflammation, and heart failure based on biomarkers.
- Assessment of endothelial function (FMD) and microcirculation (LSCI).
- Evaluation of the systolic and diastolic function of the heart based on echocardiography.
These secondary objectives aim to provide a comprehensive understanding of the effects of trimetazidine on various clinical and physiological parameters associated with heart failure with preserved ejection fraction.
Participants
The clinical trial focuses on individuals diagnosed with **heart failure with preserved ejection fraction** (HFpEF). The study population includes both male and female participants, aged between 55 and 85 years, who are classified within the New York Heart Association (NYHA) Class I to III. Participants are required to have a left ventricular ejection fraction (LVEF) of 50% or greater, as determined by echocardiographic screening. The trial does not involve a vulnerable population. Participants must have had no modification in their pharmacotherapy for at least three months prior to screening and must exhibit a high-sensitivity C-reactive protein (hsCRP) level of 1.5 mg/L or higher. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to assess the time to hospitalization or death from any cause among the participants.
Plans and Procedures
The clinical trial is designed to evaluate the impact of **trimetazidine** on endothelial function and biomarkers associated with the prognosis of heart failure with preserved ejection fraction (HFpEF). This study is a randomized, double-blind, controlled trial involving the administration of Trimeductan MR, 35 mg, modified-release tablets, and a matching placebo. The trial is expected to run until December 31, 2027, with participant recruitment starting on October 1, 2023. The primary objective is to assess the time to hospitalization for worsening heart failure or death from a cardiovascular cause, while secondary endpoints include various cardiovascular and quality of life measures.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, NYHA class, and echocardiographic findings. Follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment regimen, and to collect data on primary and secondary endpoints. The end-of-study visit will conclude the trial for each participant, ensuring all necessary data is collected and any remaining health concerns are addressed.
The expected length of participant involvement is up to 96 weeks, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial will adhere to Good Manufacturing Practice (GMP) standards, ensuring that the investigational product and placebo are indistinguishable to maintain the integrity of the double-blind design. Participants will be monitored closely throughout the study to ensure compliance and to address any potential issues promptly.
Treatment
The clinical trial involves the administration of **Trimeductan MR**, a modified-release tablet containing **trimetazidine dihydrochloride** as the active substance. Each tablet contains 35 mg of the active ingredient. The pharmaceutical form is a modified-release tablet, designed to ensure a controlled release of the active substance over time. The medication is administered orally, with a maximum daily dose of 70 mg, which equates to two tablets per day. The treatment period is set for a maximum of 96 days. The tablets are chemically based and classified as a small molecule. To maintain blinding in the study, the active treatment will be repackaged to match the appearance of the placebo, with both the external and internal packaging being identical. The repackaging process will adhere to Good Manufacturing Practice (GMP) standards to ensure quality and safety.
The study also includes a **placebo** group, which will receive a placebo designed to mimic the appearance of the Trimeductan MR tablets. The placebo is used to ensure the integrity of the double-blind study design, allowing for an unbiased comparison between the active treatment and the placebo. The placebo tablets will be indistinguishable from the active medication in terms of packaging and appearance, ensuring that neither the participants nor the investigators can identify the treatment allocation. The placebo does not contain any active pharmaceutical ingredients and serves as a control to evaluate the efficacy and safety of the active treatment.
Efficacy
Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the time to hospitalization for worsening heart failure or death from a cardiovascular cause. Secondary endpoints include time to hospitalization for cardiovascular reasons, time to hospitalization for any reason, time to cardiovascular death, and time to death from any cause. Additionally, patient-reported outcomes such as the EQ-5D score and KCCQ-12 score will be evaluated, alongside clinical assessments of NYHA Class and CCS Class.
Biomarker levels will also be measured to assess efficacy, focusing on those related to endothelial function, inflammation, and heart failure. Specific parameters include endothelial function parameters such as Flow-Mediated Dilation (FMD) and microcirculation function parameters like Laser Speckle Contrast Imaging (LSCI). Left ventricular systolic function will be evaluated through ejection fraction measurements. These assessments will be conducted at predetermined intervals throughout the trial to ensure comprehensive data collection and analysis.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Expressing willingness to participate in the study and after obtaining information about the study, signing the informed consent form for participation in the clinical study. 2. Age at study entry ≥55 years and ≤85 years; 3. NYHA Class I to III at last screening assessment. 4. Documented diagnosis of HFpEF or new diagnosis of HFpEF based on HFA-PEFF score ≥ 5 by a cardiologist during the screening phase. 5. LVEF ≥ 50% on echocardiographic screening. 6. No modification of pharmacotherapy for at least 3 months prior to screening
Exclusion Criteria
- Current treatment in another clinical trial. 2. Hypersensitivity to trimetazidine. 3. Symptoms of parkinsonism. 4. Unavailability for all visits. 5. ≥3 class in CCS scale 6. Revascularization or venous thromboembolism within 3 months prior to the screening visit. 7. Hemodynamically significant valvular disease, hypertrophic cardiomyopathy, myocarditis and pericarditis, congenital heart disease, cardiac amyloidosis. 8. Severe ventricular arrhythmias. 9. Uncontrolled BP: SBP >170 or <85 mmHg or DBP >100 mmHg at screening or randomization visit; 10. Resting heart rate (HR) >110/min or <50/min; 11. Chronic kidney disease with eGFR <30 mL/min. 12. Blood total bilirubin ≥2 times the upper limit of normal (ULN) or ALAT or AST ≥3 times the (ULN). 13. Patient life expectancy <2 years. 14. Diagnosed malignant neoplasm within 5 years prior to screening or active cancer disease. 15. Organ transplant recipient. 16. Alcoholism. 17. Active infection as assessed by the investigator 18. Severe dysfunction of the musculoskeletal system. 19. Blood concentration of TSH or fT4 exceeding by 50% the upper and/or lower limit of the reference range. 20. Taking any drugs related to the treatment of Parkinson's disease, i.e. levodopa, dopamine agonists, anticholinergics, MAO-B inhibitors, COMT inhibitors, amantadine within three months before screening. 21. A woman trying to get pregnant naturally or in vitro, or a woman who is menstruating unwilling to protect herself against unplanned pregnancy.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Poland | Not Recruiting | 01 Jan 2026 | 468 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Trimeductan MR, 35 mg, tabletki o zmodyfikowanym uwalnianiu | Test | TABLETKI O ZMODYFIKOWANYM UWALNIANIU | ORAL USE | 70 | 96 | PRD351749 |
Placebo for Trimeductan MR 35/Placebo dla Trimeductan MR 35 | Placebo | N/A | — | — | — | N/A |