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Breast CancerPhase 3CONTROLNCT05728632

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

A Phase 3 study testing Nebivolol in people with Breast Cancer and Lymphoma, Large B-Cell, Diffuse, run by Giulio Stefanini at 1 site in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nebivolol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
1 siteItaly
Study dates
1 Jan 2019to 28 Feb 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years
  • Established histologic diagnosis of breast cancer or diffuse large B-cell lymphoma
  • Planned chemotherapy with anthracyclines
  • left ventricular ejection fraction ≥55% (assessed by echocardiography)
  • Ability to provide informed consent

Who cannot join

  • Known intolerance/contraindications to betablocker therapy
  • History of coronary artery disease
  • History of cardiomyopathy
  • History of heart failure
  • Ongoing treatment with betablockers for other indications
  • Heart rate at baseline <60 beats per minute
Show all 10Show fewer
  • Arterial blood pressure at baseline <100/60 mmHg
  • Contraindications to undergo cardiac magnetic resonance (e.g., non-compatible pacemakers or metallic prosthesis)
  • Pregnancy or lactation
  • Current participation to another study

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • IRCCS Humanitas Research Hospital

    Rozzano, Milan, 20089

Other trials in Italy

About this study

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

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.

Read the detailed description

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.

Being tested
Nebivolol, Placebo
Keywords
anthracycline chemotherapy, nebivolol, cardio-oncology, cancer therapy-related cardiovascular toxicity, cardiac magnetic resonance, primary prevention, cardioprotection, cardiotoxicity
Medical subject headings
Breast Neoplasms, Lymphoma, Large B-Cell, Diffuse, Cardiotoxicity, Ventricular Dysfunction, Left

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NebivololDrug

    Also called Lobivon

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

  • PlaceboDrug

    Placebo, capsule, once daily, for 12 months

Study groups in NCT05728632
Study groupRoleWhat they receive
NebivololExperimentalnebivolol, capsule, 5 mg once daily, for 12 months
Receives: Drug: Nebivolol
PlaceboPlacebo comparatorplacebo, capsule, once daily, for 12 months
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: from baseline to 12 months

Secondary outcomes (20)

  1. 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.

    Measured: at 12-month follow-up

  2. Myocardial fibrosis assessed by Cardiac Magnetic Resonance

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

    Measured: at 12-month follow-up

  3. Myocardial edema assessed by Cardiac Magnetic Resonance

    Myocardial edema assessed by Cardiac Magnetic Resonance with T2 sequences.

    Measured: at 12-month follow-up

  4. Right ventricular ejection fraction assessed by Cardiac Magnetic Resonance

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

    Measured: at 12-month follow-up

  5. Left ventricular end-diastolic volume assessed by Cardiac Magnetic Resonance

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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  6. Left ventricular end-systolic volume assessed by Cardiac Magnetic Resonance

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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  7. Left ventricular mass assessed by Cardiac Magnetic Resonance

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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  8. Left ventricular ejection fraction assessed by Echocardiography

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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  9. 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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  10. 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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  11. Left ventricular end-diastolic volume assessed by Echocardiography

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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  12. Left ventricular end-systolic volume assessed by Echocardiography

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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  13. Serum troponin

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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  14. Serum B-type natriuretic peptide (BNP)

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

    Measured: at different timepoints (1-month, 6-month, 12-months)

  15. 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)

    Measured: at different timepoints (1-month, 6-month, 12-months)

  16. All-cause mortality

    All-cause mortality

    Measured: at 12-month follow-up

  17. 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.

    Measured: at 12-month follow-up

  18. Myocardial infarction

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

    Measured: at 12-month follow-up

  19. 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.

    Measured: at 12-month follow-up

  20. Hospitalization for heart failure

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

    Measured: at 12-month follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Feb 2023
  2. Study start1 Jan 2019
  3. Primary completion28 Feb 2023 (estimated)
  4. Study completion28 Feb 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants are randomized 1:1 to two groups in parallel for the duration of the study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05728632
Sponsor's protocol ID
012018CONTROL
Acronym
CONTROL
Status last verified
Feb 2023
First submitted
25 Jan 2023
Last updated
23 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Cannata F, Stefanini G, Carlo-Stella C, Chiarito M, Figliozzi S, Novelli L, Lisi C, Bombace S, Panico C, Cosco F, Corrado F, Masci G, Mazza R, Ricci F, Monti L, Ferrante G, Santoro A, Francone M, da Costa BR, Juni P, Condorelli G. Nebivolol versus placebo in patients undergoing anthracyclines (CONTROL Trial): rationale and study design. J Cardiovasc Med (Hagerstown). 2023 Jul 1;24(7):469-474. doi: 10.2459/JCM.0000000000001491.

    PubMed 37285278

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nebivolol in people with Breast Cancer and Lymphoma, Large B-Cell, Diffuse, run by Giulio Stefanini at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 23 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Left Ventricular Ejection Fraction reduction assessed by Cardiac Magnetic Resonance (time frame: from baseline to 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05728632, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2023.

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