Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Cardiotoxicity

Breast Diseases

Skin Diseases

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Antineoplastic Agents

All Drugs and Chemicals

Antihypertensive Agents

Anti-Infective Agents

Trastuzumab

Adrenergic beta-Antagonists

Ramipril

Angiotensin-Converting Enzyme Inhibitors

Bisoprolol

Enzyme Inhibitors

HIV Protease Inhibitors

Protease Inhibitors

Sympatholytics

Adrenergic Agents

Adrenergic beta-1 Receptor Antagonists

Adrenergic Antagonists

Neurotransmitter Agents

Placebo

Lorenzo Livi, MD, Prof

Icro Meattini, MD, Prof

The aim of the study is to analyze the protective impact on the cardiac damage of beta blockers and ACE inhibitors for breast cancer patients treated with anthracyclines-based chemotherapy with or without trastuzumab.

Over the years, due to the use of new generation therapeutic regimens, as well as the use of advanced radiation techniques, the curability of breast cancer reached an overall 10-year survival rate of approximately 80%.

Anthracyclines have a key role in the treatment of breast cancer. Many published studies showed a benefit of disease-free survival in patients with positive lymph nodes treated with anthracyclines-based regimens. Many anthracyclines and taxanes-based regimens are currently used in clinical practice in the treatment of breast cancer. Numerous randomized trials have confirmed the benefit of the addition of taxanes to anthracyclines.

Trastuzumab is a recombinant humanized monoclonal antibody with specificity for the extracellular domain of human epidermal growth factor receptor 2 (HER2). The use of trastuzumab administered sequentially or concurrently with adjuvant chemotherapy compared to chemotherapy in patients with HER2 positive was evaluated in several randomized trials. Many data concerning the incidence of adverse cardiovascular events acute, subacute and late are now available. The cardiac toxicity of anthracyclines may be acute, subacute and chronic. The acute toxicity occurs during or shortly after the infusion of the drug with arrhythmias, which in some cases leads to heart failure, pericarditis-myocarditis and electrocardiographic abnormalities. The acute toxicity is usually reversible in a dose-dependent manner. The acute and subacute toxicity are rare (1-4%). Data are available concerning clinically relevant cardiac toxicity with a chronic progressive deterioration of ventricular function up to heart failure.

Beside the cumulative dose risk factor, other unfavourable features such as advanced age, female sex, and the combination of anthracyclines and trastuzumab should be evaluated. In most cases, the late toxicity occurs within the first year following completion of chemotherapy but nevertheless the clinical manifestations can occur even after 10-20 years. This fact suggests that in women treated in (neo)adjuvant setting is strongly necessary an echocardiographic monitoring even after a longer time.

The aim of the study is to analyze the protective impact on the cardiac damage of beta blockers and ACE inhibitors for breast cancer patients treated with anthracyclines-based chemotherapy with or without trastuzumab, using myocardial strain imaging monitoring.

Both participants and Care Providers are not aware of intervention allocation.

Cardiotoxicity Prevention in Breast Cancer Patients Treated With Anthracyclines and/or Trastuzumab

Role of ACE Inhibitors and Beta Blockers as Cardiotoxicity Prevention in Breast Cancer Patients Treated With (Neo)Adjuvant Anthracyclines and/or Trastuzumab: a Four Arm, Placebo Control, Randomized Trial

Change in LVEF (3-dimensional and 2-dimensional) at time-frame

University of Florence

Azienda Ospedaliero-Universitaria Careggi

Full Professor

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasm Metastasis

Lymphoma

Leukemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphosarcoma

Chronic Graft Versus Host Disease

Intensive cardiovascular monitoring focused on prevention and early diagnosis and treatment of cardiotoxicity based in cardio-onco-hematology teams involved in cancer patient care.

Current clinical practice: cardiac care is based on the onco-hematologist criteria.

Schedule of visits: Evaluation before starting chemotherapy, at three and six months and annually for five years (eight visits: baseline, 3rd and 6th month, 1st, 2nd, 3rd, 4th and 5th years).

Assessment protocol: Anamnesis and physical examination; EKG; Echocardiogram; Biomarkers (troponin and natriuretic peptide); Structured counselling on healthy cardiac practices; Treatment optimization of cardiovascular risk factors and heart diseases; Quality of life (ECOG Performance status and Minnesota questionnaires); Interaction and management of patient care by the cardio-onco-hematology team. Moreover, cardiac MRI in centers participating in the CARTIER-MR sub-study.

Intensive cardiovascular monitoring

Schedule of visits: Evaluation before starting chemotherapy, at three and six months and annually for five years (eight visits: baseline, 3rd and 6th month, 1st, 2nd, 3rd, 4th and 5th years).

Assessment protocol: Anamnesis and physical examination; ECOG Performance status; cardiac patient care based on the onco-hematologist criteria

No intervention

Pedro L Sánchez, Ph. D.

Ana Martín-García, Ph. D.

Pilar Mazón-Ramos, MD

Sonia Velasco, MD

Ignacio Ferreira-González, MD

Dolores Mesa, MD

Fernando Alfonso-Manterola

Fernando Alfonso-Manterola, Md

Eduardo Zatarain-Nicolás

Eduardo Zatarain-Nicolás, MD

Ana Pardo-Sanz, MD

Luis F Navarro-del-Amo, MD

Carmen Jiménez-López-Guarch, MD

Cristina Mitroi, MD

Juan J Gómez-Doblas

Juan J Gómez-Doblas, MD

Gonzalo Baron-Esquivias

Gonzalo Baron-Esquivias, MD

Marina Revilla-Martínez, MD

The CARTIER study is a randomized, multicenter, open-label clinical trial comparing, in elderly patients with cancer under anti-tumoral treatment, two different cardiotoxicity prevention strategies: primary (intensive cardiovascular monitoring focused on prevention and early diagnosis and treatment of cardiotoxicity based in cardio-onco-hematology teams involved in cancer patient care) vs. secondary (current clinical practice where intensive cardiovascular monitoring is not routinely performed and cardiotoxicity patient care is based on the onco-hematologist criteria).

The primary endpoint is to determine whether this primary prevention englobing cardiovascular monitoring plus intensive multidisciplinary management is superior to the current clinical practice in reducing all cause mortality.

Other secondary objectives of the study are to analyze the impact of this intensive cardiovascular monitoring strategy on the incidence of cardiovascular mortality, oncological mortality, hospitalization and/or urgent care due to cardiovascular complications, hospitalization and/or urgent oncological care due to cancer complications, tumor progression and cost-effectiveness analysis.

A total of 514 patients ≥ 65 years old diagnosed with any of the following onco-hematological cancers, colon, breast, lymphoma, chronic lymphoma leukemia, chronic myeloid leukemia or myeloma, undergoing standardized anti-tumoral treatment, will be recruited.

The incidence of primary and secondary outcomes will be measured at 2 and 5 years

Randomized, multicenter, open-label clinical trial comparing, in elderly patient with cancer under anti-tumoral treatment, two different cardiotoxicity prevention strategies

Cardiovascular Prevention Strategies in Elderly Patients With Cancer (CARTIER Clinical Trial)

Cardiotoxicity in the Elderly. Comparative Clinical Trial Between Primary Versus Secondary Cardiovascular Prevention Strategies

Cumulative incidence of all-cause mortality

Cumulative incidence of oncological mortality

Cumulative incidence of cardiovascular mortality

Cumulative incidence of hospitalization and/or emergency care for cardiovascular cause

Cumulative incidence of hospitalization and/or emergency care for cancer cause

Incidence of tumoral recurrence or progression

Instituto de Investigación Biomédica de Salamanca

Instituto de Salud Carlos III

Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Channel Blockers

Vasodilator Agents

Cardiotonic Agents

Anti-Arrhythmia Agents

Carvedilol

Lisinopril

Metoprolol

Participants will receive a beta blocker (either metoprolol or carvedilol) and an ACE inhibitor (lisinopril) at standard doses based on tolerance starting from when they start induction therapy for AML through 90 days after the first day of the last cycle of therapy that includes an anthracycline (whether that is in the induction, re-induction, or consolidation phase of treatment). They will also undergo regular assessments via ECG/EKG and echocardiogram, and to measure troponin levels

Participants will receive standard clinical care, but will also undergo regular assessments via ECG/EKG and echocardiogram, and to measure troponin levels

Preventive beta blocker (metoprolol or carvedilol) and an ACE inhibitor (lisinopril)

Cardioprotection

Taylor Durham, RN

Cory Caldwell, RN

Taylor Durham

Cory Caldwell

Michael Keng, MD

Patients with acute myeloid leukemia (AML) often receive a drug called daunorubicin. Daunorubicin is a type of drug called an anthracycline, which increases the risk of some damage to the heart. Beta blockers and angiotensin-converting enzyme inhibitors (ACEi) are two types of drugs that are often used (and are FDA approved) to treat the type of damage to the heart caused by anthracyclines. They have also been used in some populations to prevent this type of heart damage. In this study, participants will be randomly assigned to either preventively take a beta blocker and ACEi or not to receive these. The primary purpose of the study is to look at how often people in each group develop this type of heart damage. The study investigators will also collect data about your quality of life and other changes in your heart function.

Frequency and severity of anthracycline-induced cardiotoxicity among patients receiving acute myeloid leukemia (AML) chemotherapy is unknown. We hypothesize that up-titrating study agents to maximum tolerated dosage at the time of induction (starting treatment for AML) will prevent the development of systolic dysfunction as determined on serial echocardiography.

Participants will know which group they are assigned to, and if someone in the group not receiving the preventive drugs needs these drugs for their clinical care, they will be able to receive them.

Participants in both groups will receive the standard clinical care medicines and lab tests for their AML. Everyone will have electrocardiograms (also called ECGs or EKGs) and echocardiograms before and at multiple timepoints during the study. They will also have a special blood test to see their levels of troponin, a protein that helps with muscle contractions in your heart. All participants will complete questionnaires at a few timepoints during the study to measure their quality of life. Participants in the preventive beta blocker and ACEi group will take these drugs when they're in the hospital and at home, keeping a diary of when they take it when they're at home.

The hypothesis of the study is that taking a beta blocker and ACEi during initial therapy for AML and through about 90 days after they last take an anthracycline will prevent the development of this heart problem.

Cardioprotection in AML

Phase II Trial of Cardioprotective Prophylaxis With Combination of Beta Blocker and Angiotensin-Converting Enzyme Inhibitors During Intensive Chemotherapy for Patients With Newly Diagnosed Acute Myeloid Leukemia

As measured by the FACT-Leu questionnaire

Frequency of elevation in troponin and average troponin

University of Virginia

Associate Professor

Lymphoma, Large B-Cell, Diffuse

Ventricular Dysfunction, Left

Ventricular Dysfunction

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphatic Diseases

B-cell Lymphoma

Nebivolol

Adrenergic beta-Agonists

Adrenergic Agonists

nebivolol, capsule, 5 mg once daily, for 12 months

placebo, capsule, once daily, for 12 months

Nebivolol, capsule, 5 mg once daily, for 12 months

Placebo, capsule, once daily, for 12 months

Gianluigi Condorelli, MD,PhD,Prof

Giulio G Stefanini, MD,PhD,Prof

Carmelo Carlo-Stella, MD,Prof

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.

Participants are randomized 1:1 to two groups in parallel for the duration of the study

Patients, treating physicians, investigators, and outcome assessors are masked to the allocated treatment.

Cardioprotective Effects of Nebivolol Versus Placebo in Patients Undergoing Chemotherapy With Anthracyclines

Cardioprotective Effects of Nebivolol Versus Placebo in Patients Undergoing Chemotherapy With Anthracyclines (CONTROL Trial)

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).

Left ventricular ejection fraction (unit of measurement: %) assessed by Cardiac Magnetic Resonance at 12-month follow-up.

Myocardial fibrosis assessed by Cardiac Magnetic Resonance with T1-mapping sequences and with Late Gadolinium Enhancement images.

Myocardial edema assessed by Cardiac Magnetic Resonance with T2 sequences.

Right ventricular ejection fraction (unit of measurement: %) assessed by Cardiac Magnetic Resonance

Left ventricular end-diastolic volume (unit of measurement: ml) assessed by Cardiac Magnetic Resonance

Left ventricular end-systolic volume (unit of measurement: ml) assessed by Cardiac Magnetic Resonance

Left ventricular mass (unit of measurement: g/m²) assessed by Cardiac Magnetic Resonance

Left ventricular ejection fraction (unit of measurement: %) assessed by Echocardiography

Left ventricular diastolic function assessed by Echocardiography according to Guidelines of European Association of Cardiovascular Imaging / American Society of Echocardiography

Right ventricular systolic function assessed by Echocardiography according to Guidelines of European Association of Cardiovascular Imaging / American Society of Echocardiography

Left ventricular end-diastolic volume (unit of measurement: ml) assessed by Echocardiography

Left ventricular end-systolic volume (unit of measurement: ml) assessed by Echocardiography

Serum high-sensitivity cardiac troponin I levels (unit of measurement: ng/L)

Serum B-type natriuretic peptide (BNP) (unit of measurement: pg/mL)

Serum N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) levels (unit of measurement: pg/mL)

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.

Myocardial infarction will be defined according to the 3rd Universal Definition.

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.

Hospitalization for heart failure will be defined as any unplanned hospital readmission due to signs and symptoms of heart failure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cardiotoxicity Prevention in Breast Cancer Patients Treated With Anthracyclines and/or Trastuzumab	NCT02236806	Breast Cancer Cardiotoxicity	Bisoprolol Ramipril Placebo	18 Years -	Azienda Ospedaliero-Universitaria Careggi
Cardiovascular Prevention Strategies in Elderly Patients With Cancer (CARTIER Clinical Trial)	NCT03711110	Cancer (Colon C... Elderly Antineoplastic ... Cardiotoxicity	Intensive cardi... No intervention	65 Years -	Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León
Cardioprotection in AML	NCT04977180	AML Acute Myeloid L...	Cardioprotectio...	18 Years -	University of Virginia
Cardiotoxicity Prevention in Breast Cancer Patients Treated With Anthracyclines and/or Trastuzumab	NCT02236806	Breast Cancer Cardiotoxicity	Bisoprolol Ramipril Placebo	18 Years -	Azienda Ospedaliero-Universitaria Careggi
Cardioprotective Effects of Nebivolol Versus Placebo in Patients Undergoing Chemotherapy With Anthracyclines	NCT05728632	Breast Cancer Lymphoma, Large... Cardiotoxicity Left Ventricula... Chemotherapy Ef...	Nebivolol Placebo	18 Years -	Humanitas Hospital, Italy
Cardioprotection in AML	NCT04977180	AML Acute Myeloid L...	Cardioprotectio...	18 Years -	University of Virginia

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