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

NCT ID: NCT05728632

Last Updated: 2023-02-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-01
• Study Completion Date: 2023-02-28

Brief 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. 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.

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.

Conditions

Breast Cancer; Lymphoma, Large B-Cell, Diffuse; Cardiotoxicity; Left Ventricular Dysfunction; Chemotherapy Effect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Nebivolol

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

Group Type: EXPERIMENTAL

Nebivolol

Intervention Type: DRUG

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

Placebo

placebo, capsule, once daily, for 12 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo, capsule, once daily, for 12 months

Interventions

Nebivolol

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

Intervention Type: DRUG

Placebo

Placebo, capsule, once daily, for 12 months

Intervention Type: DRUG

Other Intervention Names

Lobivon

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agenzia Italiana del Farmaco

OTHER_GOV

Sponsor Role: collaborator

Giulio Stefanini

OTHER

Sponsor Role: lead

Responsible Party

Giulio Stefanini

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gianluigi Condorelli, MD,PhD,Prof

Role: PRINCIPAL_INVESTIGATOR

IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy

Giulio G Stefanini, MD,PhD,Prof

Role: PRINCIPAL_INVESTIGATOR

IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy

Carmelo Carlo-Stella, MD,Prof

Role: PRINCIPAL_INVESTIGATOR

IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy

Locations

IRCCS Humanitas Research Hospital

Rozzano, Milan, Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 37285278 (View on PubMed)

Other Identifiers

012018CONTROL

Identifier Type: -

Identifier Source: org_study_id