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

NCT05728632 | Unknown Phase 3 DMC

• 1 other identifier: 012018CONTROL
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

anthracycline chemotherapy; nebivolol; cardio-oncology; cancer therapy-related cardiovascular toxicity; cardiac magnetic resonance; primary prevention; cardioprotection; cardiotoxicity

Outcome Measures

Primary Outcomes (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).

  from baseline to 12 months

Secondary Outcomes (20)

• Left ventricular ejection fraction assessed by Cardiac Magnetic Resonance

  at 12-month follow-up

• Myocardial fibrosis assessed by Cardiac Magnetic Resonance

  at 12-month follow-up

• Myocardial edema assessed by Cardiac Magnetic Resonance

  at 12-month follow-up

• Right ventricular ejection fraction assessed by Cardiac Magnetic Resonance

  at 12-month follow-up

• Left ventricular end-diastolic volume assessed by Cardiac Magnetic Resonance

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

Study Arms (2)

Nebivolol

EXPERIMENTAL

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

Drug: Nebivolol

Placebo

PLACEBO COMPARATOR

placebo, capsule, once daily, for 12 months

Drug: Placebo

Interventions

Nebivolol DRUG

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

Also known as: Lobivon

Nebivolol

Placebo DRUG

Placebo, capsule, once daily, for 12 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Giulio Stefanini: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (1)

IRCCS Humanitas Research Hospital

Rozzano, Milan, 20089, Italy

Location

Related Publications (1)

• 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.

  PMID: 37285278 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Lymphoma, Large B-Cell, Diffuse; Cardiotoxicity; Ventricular Dysfunction, Left

Interventions

Nebivolol

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Gianluigi Condorelli, MD,PhD,Prof

  IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy

  PRINCIPAL INVESTIGATOR

• Giulio G Stefanini, MD,PhD,Prof

  IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy

  PRINCIPAL INVESTIGATOR

• Carmelo Carlo-Stella, MD,Prof

  IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients, treating physicians, investigators, and outcome assessors are masked to the allocated treatment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

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

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: February 15, 2023
• Study Start: January 1, 2019
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: February 23, 2023

Record last verified: 2023-02

Locations

IT (1)