A Phase 3 interventional study of Nebivolol and Placebo in Breast Cancer, Lymphoma, Large B-Cell, Diffuse and Cardiotoxicity, sponsored by Giulio Stefanini. Status unknown at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-02-23.
Sponsored by Giulio Stefanini · Phase 3, Interventional, and Prevention
As the cancer-related prognosis improves thanks to recent advances in cancer-targeted therapies, the prognostic burden of chemotherapy-related complications - including cardiotoxicity - is increasingly recognised. So far, the evidence supporting pharmacological preventive strategies in cardio-oncology has been inconsistent and conflicting, and there is a clear need for well-designed trials with novel interventions. In this study, by using cardiac magnetic resonance, the investigators want to assess if a commonly used beta-blocker with a unique pharmacological profile, i.e. nebivolol, can prevent cardiac dysfunction in patients with breast cancer or diffuse large B-cell lymphoma undergoing chemotherapy with anthracyclines.
During the last decades, major efforts have been made in the field of cancer therapy to improve prognosis and quality of life of patients treated with any sort of chemotherapy. Cardiotoxicity represents one of the most relevant adverse effects of chemotherapy, primarily in patients treated with anthracyclines. The potential protective role of cardiovascular medications in the prevention of cardiotoxicity associated with anthracyclines chemotherapy is still a matter of debate since evidence in this field are scarce and largely inconclusive. Indeed, prior studies were often limited by a non-blinded design or an echocardiography-based assessment of left ventricular ejection fraction (with a relevant inter and intra-operator variability). The primary objective of the trial is to evaluate the cardioprotective effects of the betablocker nebivolol in an individually randomized, parallel, placebo-controlled, double-blinded (patient, treating physician, investigator, outcomes assessor, statistician), superiority trial in patients with a solid tumor (i.e., breast cancer) or a hematologic malignancy (i.e., diffuse large B cell lymphoma) who have a normal cardiac function as assessed by echocardiography and will receive anthracyclines as part of their first-line chemotherapy program. Indeed, recent evidence suggests that anthracycline cardiotoxicity seems mainly due to an anthracycline-induced dysregulation of mitochondrial activity and metabolism in cardiomyocytes. Nebivolol has a distinctive profile among beta-blockers, with the unique power of increasing the nitric oxide bioavailability. Nebivolol-induced nitric oxide release has shown favourable effects in terms of antioxidant activity, cardiac neo-angiogenesis, mitochondrial and endothelial protection. On this basis, the individually randomized, parallel, placebo-controlled, double-blinded (patient, treating physician, investigator, outcomes assessor, statistician), superiority CONTROL trial will assess the cardioprotective effects of a commonly used betablocker (nebivolol) in patients with baseline normal left ventricular systolic function receiving anthracycline chemotherapy as first-line chemotherapy for breast cancer or diffuse large B-cell lymphoma. The assessment of left ventricular ejection fraction and related endpoints will be performed with cardiac magnetic resonance.
1,390 studies on the registry are indexed under Lymphoma, Large B-Cell, Diffuse; 350 are open to participants now.
This study's enrollment of 80 is above the median of 47 across 1,185 interventional studies indexed under Lymphoma, Large B-Cell, Diffuse.
Browse Lymphoma, Large B-Cell, Diffuse studies →This is the only study on the registry with Giulio Stefanini as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
nebivolol, capsule, 5 mg once daily, for 12 months
Drug: Nebivolol
placebo, capsule, once daily, for 12 months
Drug: Placebo
Nebivolol, capsule, 5 mg once daily, for 12 months
Also known as: Lobivon
Placebo, capsule, once daily, for 12 months
Left Ventricular Ejection Fraction reduction assessed by Cardiac Magnetic Resonance
The primary endpoint is defined as Left Ventricular Ejection Fraction (LVEF) reduction (unit of measurement: %) assessed by Cardiac Magnetic Resonance at 12 months of follow-up. LVEF reduction is defined as the difference between LVEF at baseline and LVEF at 12 months follow-up (LVEF reduction = Baseline LVEF - 12 months LVEF).
Time frame: from baseline to 12 months
Left ventricular ejection fraction assessed by Cardiac Magnetic Resonance
Left ventricular ejection fraction (unit of measurement: %) assessed by Cardiac Magnetic Resonance at 12-month follow-up.
Time frame: at 12-month follow-up
Myocardial fibrosis assessed by Cardiac Magnetic Resonance
Myocardial fibrosis assessed by Cardiac Magnetic Resonance with T1-mapping sequences and with Late Gadolinium Enhancement images.
Time frame: at 12-month follow-up
Myocardial edema assessed by Cardiac Magnetic Resonance
Myocardial edema assessed by Cardiac Magnetic Resonance with T2 sequences.
Time frame: at 12-month follow-up
Right ventricular ejection fraction assessed by Cardiac Magnetic Resonance
Right ventricular ejection fraction (unit of measurement: %) assessed by Cardiac Magnetic Resonance
Time frame: at 12-month follow-up
Left ventricular end-diastolic volume assessed by Cardiac Magnetic Resonance
Left ventricular end-diastolic volume (unit of measurement: ml) assessed by Cardiac Magnetic Resonance
Time frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-systolic volume assessed by Cardiac Magnetic Resonance
Left ventricular end-systolic volume (unit of measurement: ml) assessed by Cardiac Magnetic Resonance
Time frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular mass assessed by Cardiac Magnetic Resonance
Left ventricular mass (unit of measurement: g/m²) assessed by Cardiac Magnetic Resonance
Time frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular ejection fraction assessed by Echocardiography
Left ventricular ejection fraction (unit of measurement: %) assessed by Echocardiography
Time frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular diastolic function assessed by Echocardiography
Left ventricular diastolic function assessed by Echocardiography according to Guidelines of European Association of Cardiovascular Imaging / American Society of Echocardiography
Time frame: at different timepoints (1-month, 6-month, 12-months)
Right ventricular systolic function assessed by Echocardiography
Right ventricular systolic function assessed by Echocardiography according to Guidelines of European Association of Cardiovascular Imaging / American Society of Echocardiography
Time frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-diastolic volume assessed by Echocardiography
Left ventricular end-diastolic volume (unit of measurement: ml) assessed by Echocardiography
Time frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-systolic volume assessed by Echocardiography
Left ventricular end-systolic volume (unit of measurement: ml) assessed by Echocardiography
Time frame: at different timepoints (1-month, 6-month, 12-months)
Serum troponin
Serum high-sensitivity cardiac troponin I levels (unit of measurement: ng/L)
Time frame: at different timepoints (1-month, 6-month, 12-months)
Serum B-type natriuretic peptide (BNP)
Serum B-type natriuretic peptide (BNP) (unit of measurement: pg/mL)
Time frame: at different timepoints (1-month, 6-month, 12-months)
Serum N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP)
Serum N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) levels (unit of measurement: pg/mL)
Time frame: at different timepoints (1-month, 6-month, 12-months)
All-cause mortality
All-cause mortality
Time frame: at 12-month follow-up
Cardiovascular mortality
Cardiovascular mortality or death will be defined as any death due to immediate cardiovascular cause (e.g. myocardial infarction, low-output failure, arrhythmia). Unwitnessed death and death of unknown cause will be classified as cardiac death.
Time frame: at 12-month follow-up
Myocardial infarction
Myocardial infarction will be defined according to the 3rd Universal Definition.
Time frame: at 12-month follow-up
Cerebrovascular events
Cerebrovascular events will be defined as follows: * Transient ischemic attack: rapidly developed clinical signs of global disturbance of cerebral function lasting fewer \<24 hours, regardless of the presence of an acute clinically relevant brain lesion in imaging. * Ischemic stroke: rapidly developed clinical signs of focal or global disturbance of cerebral function lasting \>24 hours with imaging of an acute clinically relevant brain lesion. * Intracerebral haemorrhage: diagnosis must be confirmed by cerebral imaging.
Time frame: at 12-month follow-up
Hospitalization for heart failure
Hospitalization for heart failure will be defined as any unplanned hospital readmission due to signs and symptoms of heart failure.
Time frame: at 12-month follow-up
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Lymphoma, Large B-Cell, Diffuse→