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

February 21, 2023 updated by: Giulio Stefanini

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Milan
      • Rozzano, Milan, Italy, 20089
        • Irccs Humanitas Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Nebivolol
nebivolol, capsule, 5 mg once daily, for 12 months
Drug: Nebivolol
Nebivolol, capsule, 5 mg once daily, for 12 months
Other Names:
  • Lobivon
Placebo Comparator: Placebo
placebo, capsule, once daily, for 12 months
Drug: Placebo
Placebo, capsule, once daily, for 12 months

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Left Ventricular Ejection Fraction reduction assessed by Cardiac Magnetic Resonance
Time Frame: from baseline to 12 months

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).
from baseline to 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Left ventricular ejection fraction assessed by Cardiac Magnetic Resonance
Time Frame: at 12-month follow-up
Left ventricular ejection fraction (unit of measurement: %) assessed by Cardiac Magnetic Resonance at 12-month follow-up.
at 12-month follow-up
Myocardial fibrosis assessed by Cardiac Magnetic Resonance
Time Frame: at 12-month follow-up
Myocardial fibrosis assessed by Cardiac Magnetic Resonance with T1-mapping sequences and with Late Gadolinium Enhancement images.
at 12-month follow-up
Myocardial edema assessed by Cardiac Magnetic Resonance
Time Frame: at 12-month follow-up
Myocardial edema assessed by Cardiac Magnetic Resonance with T2 sequences.
at 12-month follow-up
Right ventricular ejection fraction assessed by Cardiac Magnetic Resonance
Time Frame: at 12-month follow-up
Right ventricular ejection fraction (unit of measurement: %) assessed by Cardiac Magnetic Resonance
at 12-month follow-up
Left ventricular end-diastolic volume assessed by Cardiac Magnetic Resonance
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-diastolic volume (unit of measurement: ml) assessed by Cardiac Magnetic Resonance
at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-systolic volume assessed by Cardiac Magnetic Resonance
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-systolic volume (unit of measurement: ml) assessed by Cardiac Magnetic Resonance
at different timepoints (1-month, 6-month, 12-months)
Left ventricular mass assessed by Cardiac Magnetic Resonance
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular mass (unit of measurement: g/m²) assessed by Cardiac Magnetic Resonance
at different timepoints (1-month, 6-month, 12-months)
Left ventricular ejection fraction assessed by Echocardiography
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular ejection fraction (unit of measurement: %) assessed by Echocardiography
at different timepoints (1-month, 6-month, 12-months)
Left ventricular diastolic function assessed by Echocardiography
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular diastolic function assessed by Echocardiography according to Guidelines of European Association of Cardiovascular Imaging / American Society of Echocardiography
at different timepoints (1-month, 6-month, 12-months)
Right ventricular systolic function assessed by Echocardiography
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Right ventricular systolic function assessed by Echocardiography according to Guidelines of European Association of Cardiovascular Imaging / American Society of Echocardiography
at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-diastolic volume assessed by Echocardiography
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-diastolic volume (unit of measurement: ml) assessed by Echocardiography
at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-systolic volume assessed by Echocardiography
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Left ventricular end-systolic volume (unit of measurement: ml) assessed by Echocardiography
at different timepoints (1-month, 6-month, 12-months)
Serum troponin
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Serum high-sensitivity cardiac troponin I levels (unit of measurement: ng/L)
at different timepoints (1-month, 6-month, 12-months)
Serum B-type natriuretic peptide (BNP)
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Serum B-type natriuretic peptide (BNP) (unit of measurement: pg/mL)
at different timepoints (1-month, 6-month, 12-months)
Serum N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP)
Time Frame: at different timepoints (1-month, 6-month, 12-months)
Serum N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) levels (unit of measurement: pg/mL)
at different timepoints (1-month, 6-month, 12-months)
All-cause mortality
Time Frame: at 12-month follow-up
All-cause mortality
at 12-month follow-up
Cardiovascular mortality
Time Frame: at 12-month follow-up
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.
at 12-month follow-up
Myocardial infarction
Time Frame: at 12-month follow-up
Myocardial infarction will be defined according to the 3rd Universal Definition.
at 12-month follow-up
Cerebrovascular events
Time Frame: at 12-month follow-up

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.
at 12-month follow-up
Hospitalization for heart failure
Time Frame: at 12-month follow-up
Hospitalization for heart failure will be defined as any unplanned hospital readmission due to signs and symptoms of heart failure.
at 12-month follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Giulio Stefanini

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Agenzia Italiana del Farmaco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2019

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2023

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 25, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 15, 2023

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 23, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 21, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 012018CONTROL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings