Observational Trial of Cardiotoxicity in Patients Undergoing Chemotherapy.

Study Overview
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Brief Summary
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Advances in treatment have led to improved survival of patients with cancer, but have also increased morbidity and mortality due to cancer treatment side effects. Cardiotoxicity is one the most frequent side effect which may lead to premature morbidity and death among cancer survivors. The most concerning cardiovascular complications of cancer therapy is myocardial dysfunction, leading to heart failure, and fatal arrhythmias, especially those induced by QT-prolonging drugs. PROMETEY (PROspective Multidisciplinary obsErvational Trial of cardiotoxicity in patiEnts undergoing anticancer therapy) - is Russian multicenter observational study assessing cardiotoxicity and its clinical, biochemical and genetic factors in patients on cancer therapy. The objectives of the study are: to reveal prevalence of cardiotoxic effects of cancer therapy in routine clinical practice in Russian Federation, to assess contribution of these effects to mortality of patients on cancer therapy, to evaluate clinical and economic consequences of cardiotoxicity in patients with cancer, to develop an individualized model of cardiotoxicity risk factors based on clinical and laboratory parameters. Patients: 400 cancer patients with toxic cardiomyopathy and 100 patients with idiopathic or family dilated cardiomyopathy. Study duration: 60 months. All patients will undergo complex examination after signing informed consent form(ICF): physical exam, echocardiography with speckle tracking analysis, ambulatory 48-hours ECG monitoring, biochemistry, analysis of biomarkers of myocardial injury, fibrosis and inflammation. Primary endpoint: all-cause mortality, heart transplantation, cardioverter-defibrillator implantation, hospitalization with heart failure decompensation. Secondary endpoints: thromboembolism, fatal/ nonfatal myocardial infarction, stroke, sudden cardiac death, surgical therapy of heart failure or arrhythmias, cardiovascular death, all-cause mortality, heart transplantation, cardioverter-defibrillator implantation.

Official Title
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Prospective Multidisciplinary Observational Trial of Cardiotoxicity in Patients Undergoing Anticancer Therapy.

Conditions
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Cardiotoxicity, Heart Failure, Dilated Cardiomyopathy

Intervention / Treatment
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* Diagnostic Test: Echocardiography with speckle tracking analysis.
* Diagnostic Test: 48-hour ECG monitoring.
* Diagnostic Test: Blood samples analysis.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: written informed consent form (ICF), Eastern Cooperative Oncology Group (ECOG) scale 0-3, patients with verified cancer on or planned to be on chemotherapy including anthracyclines, sufficient bone marrow function, including: absolute neutrophils > 1.5*10^9/l, platelets > 100*10^9/l, hemoglobin > 9 g/dl, sufficient liver function, including: total bilirubin < 1.5*upper normal value, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 upper normal value, sufficient renal function, including: creatinine clearance > 50 ml/min. For control group: verified non-toxic dilated cardiomyopathy. Exclusion Criteria: refusal of patient, sepsis, coma, delirium, mental disorders, left chest radiation therapy, metastases in central nervous system.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| cancer survivors with heart failure and/or fatal arrhythmias<br>Patients undergoing cancer therapy for the last 3-4 years with signs of heart failure and/or life-threatening arrhythmias. Administered interventions: physical examination, echocardiography with speckle tracking analysis, 48-hour ECG monitoring, blood samples analysis for biochemistry, biomarkers of myocardial damage, fibrosis and inflammation. | Diagnostic Test: Echocardiography with speckle tracking analysis.<br>* Transthoracic echocardiography with speckle tracking analysis.<br>Diagnostic Test: 48-hour ECG monitoring.<br>* Ambulatory 48-hour electrocardiography monitoring.<br>Diagnostic Test: Blood samples analysis.<br>* Analysis of blood samples for biochemistry, biomarkers of myocardial damage, fibrosis and inflammation.<br>|
| Cancer survivors without complications<br>Patients undergoing cancer therapy for the last 3-4 years without signs of heart failure and/or life-threatening arrhythmias. Administered interventions: physical examination, echocardiography with speckle tracking analysis, 48-hour ECG monitoring, blood samples analysis for biochemistry, biomarkers of myocardial damage, fibrosis and inflammation. | Diagnostic Test: Echocardiography with speckle tracking analysis.<br>* Transthoracic echocardiography with speckle tracking analysis.<br>Diagnostic Test: 48-hour ECG monitoring.<br>* Ambulatory 48-hour electrocardiography monitoring.<br>Diagnostic Test: Blood samples analysis.<br>* Analysis of blood samples for biochemistry, biomarkers of myocardial damage, fibrosis and inflammation.<br>|
| Cancer patients before chemotherapy<br>Cancer patients before administered chemotherapy. Interventions: physical examination, echocardiography with speckle tracking analysis, 48-hour ECG monitoring, blood samples analysis for biochemistry, biomarkers of myocardial damage, fibrosis and inflammation. | Diagnostic Test: Echocardiography with speckle tracking analysis.<br>* Transthoracic echocardiography with speckle tracking analysis.<br>Diagnostic Test: 48-hour ECG monitoring.<br>* Ambulatory 48-hour electrocardiography monitoring.<br>Diagnostic Test: Blood samples analysis.<br>* Analysis of blood samples for biochemistry, biomarkers of myocardial damage, fibrosis and inflammation.<br>|
| Patients with non-toxic dilated cardiomyopathy (control).<br>Patients with non-toxic dilated cardiomyopathy. Administered interventions: physical examination, echocardiography with speckle tracking analysis, 48-hour ECG monitoring, blood samples analysis for biochemistry, biomarkers of myocardial damage, fibrosis and inflammation. | Diagnostic Test: Echocardiography with speckle tracking analysis.<br>* Transthoracic echocardiography with speckle tracking analysis.<br>Diagnostic Test: 48-hour ECG monitoring.<br>* Ambulatory 48-hour electrocardiography monitoring.<br>Diagnostic Test: Blood samples analysis.<br>* Analysis of blood samples for biochemistry, biomarkers of myocardial damage, fibrosis and inflammation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Death of patient from all causes. | During all observational period (60 months) | 
| Heart transplantation | Heart transplantation associated with heart failure or toxic cardiomyopathy decompensation. | During all observational period (60 months). | 
| Cardioverter-defibrillator implantation | Implantation of cardioverter-defibrillator associated with life-threatening ventricular arrhythmias. | During all observational period (60 months). | 
| Hospitalization with heart failure decompensation | Hospitalization of patient due to decompensation of heart failure. | During all observational period (60 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thromboembolism. | Venous thromboembolism associated with cancer disease. | During all observational period (60 months). | 
| Myocardial infarction | Fatal/nonfatal myocardial infarction. | During all observational period (60 months). | 
| Stroke | Stroke | During all observational period (60 months). | 
| Sudden cardiac death | Sudden cardiac death associated with fatal arrhythmias. | During all observational period (60 months). | 
| Surgical therapy of heart failure or arrhythmias | Surgical therapy of heart failure or arrhythmias. | During all observational period (60 months). | 
| Cardiovascular death | Death of patient associated with cardiovascular disease. | During all observational period (60 months). |