Serial Cardiac Magnetic Resonance Imaging (CMR) With Contrast Agents and Biomarker Analysis for the Detection of Cardiotoxicity Under Anthracycline-containing Cancer Therapy - A Monocentric, Low Interventional Phase IV Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 93
- 试验地点
- 1
- 主要终点
- Change of T2-weighted myocardial relaxation time in cardiac magnetic resonance imaging
研究概览
简要总结
The goal of the trial is the early detection of cardiotoxicity in patients treated with anthracycline-based chemotherapy. Current diagnostics, such as troponin T, NT-pro-BNP, electrocardiogram, and echocardiography, are not able to identify early myocardial damage. Therefore, this study aims to identify early myocardial damage by using cardiac magnetic resonance imaging.
The primary endpoint of this study is the change in relaxation times in CMR before, during, and after therapy.
Furthermore, the study analyzes:
- other abnormal results in CMR
- changes in troponin T and NT-pro-BNP
- changes in global longitudinal strain in echocardiography and correlation with results of CMR
- detection of new biomarkers in blood, urine, or stool
详细描述
The goal of the trial is the early detection of cardiotoxicity in patients treated with anthracycline-based chemotherapy as standard of care therapy. For clarification: Standard anthracycline-based chemotherapy is administered independently of the study and is not the subject of this study, but rather is its basis. No investigational medicinal products are being tested in this clinical trial; instead only diagnostic procedures are being investigated.
Since current diagnostic methods-such as troponin T, NT-proBNP, electrocardiography, and echocardiography-are limited in their ability to detect early myocardial injury, the study aims to identify early myocardial damage using cardiac magnetic resonance imaging (CMR).
Enrolled participants will be stratified into risk groups using the HFA-ICOS score and-depending on the risk category-monitored according to current ESC guidelines using electrocardiography, echocardiography, and serial measurements of troponin T and NT-proBNP.
Preclinical data suggest that anthracyclines may impair myocardial function not only as a result of cumulative dosage over time but also during the early stages of therapy. The investigators therefore evaluate the use of CMR for the early detection of myocardial alterations during anthracycline therapy.
CMR examinations will be scheduled according to the administered cumulative dose of anthracyclines. Following a baseline evaluation prior to the initiation of therapy, the first follow-up CMR examination will be performed after approximately half of the preplanned cumulative anthracycline dose has been administered. A third CMR examination will be conducted after completion of therapy. Twelve months after therapy completion, an end-of-study CMR examination will be performed to assess persistent myocardial changes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •- Patients with a recommendation for antineoplastic therapy including at least four administrations of an anthracycline
排除标准
- •Inability to provide informed consent
- •Prior administration of an anthracycline
- •Administration of cardiotoxic drugs within the last six months, such as:
- •High-dose cyclophosphamide (>1,000 mg/m² or >10 mg/kg)
- •HER2 inhibitors
- •VEGF inhibitors
- •BCR-ABL inhibitors
- •BRAF inhibitors
- •MEK inhibitors
- •Immune checkpoint inhibitors (CTLA-4 inhibitors, PD-1 inhibitors, PD-L1 inhibitors)
- •Planned invasive cardiac intervention during the study period
- •Cardiac involvement of an underlying disease, e.g. amyloidosis
- •Treatment with fewer than four administrations of anthracyclines
- •Treatment with a liposomal anthracycline formulation
- •Treatment in which anthracyclines are not administered in every chemotherapy cycle
- •Thoracic radiation involving the heart prior to anthracycline administration
- •Participation in another clinical study concurrently or within the last three months
- •Renal impairment with a GFR < 30 ml/min/1.73 m²
- •Patients in the perioperative phase of liver transplantation
- •Contraindications to cardiac magnetic resonance imaging, such as metallic implants (e.g. cardiac pacemaker)
- •Pregnancy or breastfeeding
- •Hypersensitivity or intolerance to gadolinium-based contrast agents
- •Vulnerable populations (individuals unable to protect their own interests, prisoners)
研究组 & 干预措施
Serial cardiac magnetic resonance imaging (CMR)
In this study, cardiac magnetic resonance imaging (CMR) is used as the primary tool for detecting possible anthracycline-induced cardiotoxicity without affecting standard oncological therapy. Before starting anthracycline-based therapy, a baseline CMR is performed, supplemented by echocardiography (TTE), ECG, and biomarker determination. Further CMR examinations are performed for mid-point analysis after half of the planned chemotherapy cycles, as well as 12-14 weeks and 12 months after the end of therapy. The timing depends on the individual chemotherapy regimen, with CMR scheduled on the same day always taking place before anthracycline administration.
The CMR examinations are used for structural and functional assessment of the heart and are combined with other diagnostic procedures (TTE, ECG, biomarkers, biosampling) to detect early changes in heart function and systematically monitor the course of potential cardiotoxic effects during therapy.
干预措施: CMR based measurement of cardiotoxicity (Diagnostic Test)
Serial cardiac magnetic resonance imaging (CMR)
In this study, cardiac magnetic resonance imaging (CMR) is used as the primary tool for detecting possible anthracycline-induced cardiotoxicity without affecting standard oncological therapy. Before starting anthracycline-based therapy, a baseline CMR is performed, supplemented by echocardiography (TTE), ECG, and biomarker determination. Further CMR examinations are performed for mid-point analysis after half of the planned chemotherapy cycles, as well as 12-14 weeks and 12 months after the end of therapy. The timing depends on the individual chemotherapy regimen, with CMR scheduled on the same day always taking place before anthracycline administration.
The CMR examinations are used for structural and functional assessment of the heart and are combined with other diagnostic procedures (TTE, ECG, biomarkers, biosampling) to detect early changes in heart function and systematically monitor the course of potential cardiotoxic effects during therapy.
干预措施: biosampling for scientific research in study-specific biobank (Other)
结局指标
主要结局
Change of T2-weighted myocardial relaxation time in cardiac magnetic resonance imaging
时间窗: Baseline (before anthracycline administration), after 4-9 weeks (depending on the anthracycline-based treatment regimen used), 3 months after completion of therapy, and 12 months after completion of therapy.
T2 mapping using an ECG-triggered T2-prepared SSFP sequence before contrast agent administration. The evaluation is performed independently by two examiners with manual marking of endocardial and epicardial boundaries.
次要结局
- abnormal CMR findings regarding morphology and function(Baseline (before anthracycline administration), after 4-9 weeks (depending on the anthracycline-based treatment regimen used), 3 months after completion of therapy, and 12 months after completion of therapy.)
- abnormal CMR findings regarding late gadolinium enhancement (LGE)(Baseline (before anthracycline administration), after 4-9 weeks (depending on the anthracycline-based treatment regimen used), 3 months after completion of therapy, and 12 months after completion of therapy.)
- abnormal CMR findings regarding additional parametric mapping (T1-weighted relaxation times, extracellular volume)(Baseline (before anthracycline administration), after 4-9 weeks (depending on the anthracycline-based treatment regimen used), 3 months after completion of therapy, and 12 months after completion of therapy.)
- Troponin T and NT-proBNP levels before, during, and after completion of anthracycline-based chemotherapy, correlated with CMR findings(Baseline (before anthracycline administration), after 4-9 weeks (depending on the anthracycline-based treatment regimen used), 3 months after completion of therapy, and 12 months after completion of therapy.)
- Echocardiographically assessed global longitudinal strain before, during, and after completion of anthracycline-based chemotherapy, correlated with CMR findings.(Baseline (before anthracycline administration), after 4-9 weeks (depending on the anthracycline-based treatment regimen used), 3 months after completion of therapy, and 12 months after completion of therapy.)