Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity

NCT ID: NCT05175066

Last Updated: 2022-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-12
• Study Completion Date: 2021-12-02

Brief Summary

Anthracyclines are one of the most well-known and effective drugs used to treat malignancies.The most important limiting factor in the use of this drug is its cardiac toxicity which includes cardiomyopathy and congestive heart failure. Bisoprlol is a β1-specific β-blocker that can reduce cardiac overload and also have anti-inflammatory antioxidant effects and can reduce reactive oxygen metabolites so it can be used as a cardioprotective agent in patients with a high risk of heart failure. To the best of our knowledge, no study has been performed to evaluate the prophylactic effect of bisoprolol solely in patients under chemotherapy with anthracyclines. This study is aimed to evaluate the cardioprotective role of bisoprolol in patients with non-metastatic breast cancer receiving doxorubicin, by measuring global longitudinal strain before and after treatment.

Detailed Description

This study was a double-blinded randomized control trial that was conducted at the Iran University of medical sciences.

Sixty-three patients that was diagnosed with non-metastatic breast cancer and anthracycline-based chemotherapy were planned for them were enrolled in this study. The exclusion criteria included: established ischemic heart disease, baseline LVEF <50%, cardiomyopathy (restrictive, dilated, or hypertrophic) detected by transthoracic echocardiography, moderate or severe valvular disease, prior chemotherapy, presence of contraindication for beta-blockers and cardiac arrhythmias and lack of patient compliance. Also, all the patients that had consumed angiotensin-converting enzyme Inhibitors, angiotensin receptor Inhibitors,diuretics, statins,other beta-blockers or non-dihydropyridin calcium channel blockers were excluded.Pateinets were randomly divided into two case and control groups by a box randomization method. At first, case group was comprised of 31 patients who were given bisoprolol at a dose of 1.25 mg daily, and in the absence of clinical symptoms and heart rate above 60 and systolic blood pressure above 100, 1.25 mg was added to the therapeutic dose every 2 weeks to reach 5 mg daily.

Two placebo tablets in similar shape and color to bisoprolol were given on a daily basis to each of the remaining 32 patients as the control group. Both bisoprolol and placebo administration was started since 7 days before start of chemotherapy and continued for 6 months.The study protocol was explained to each patient, and written consent was obtained from all patients.

chemotherapy regimen included doxorubicin (60 mg/m 2) and cyclophosphamide (600 mg/m2) followed by docetaxel (100 mg/m2) that was completed in four consecutive cycles, each cycle lasted 21 days and the cumulative dose of doxorubicin reached 240 mg/m2.

None of patients were treated with hormonal therapy or trastuzumab during the study period. Patients were visited by a cardiologist at baseline, before chemotherapy and every month after start of treatment. The presence of drug-related side effects (in particular hypotension and bradycardia) if any were recorded. The occurrence of heart failure, hospitalization and death were also collected.

Transthoracic echocardiography was performed 1 week prior to the chemotherapy and 1 week after the fourth doxorubicin cycle. Strain, strain-rate parameters and LVEF wereevaluated. A decrease of more than 10-50% in LVEF was considered as a criterion for discontinuing chemotherapy with anthracycline and patients were excluded from the study.

Blind conventional 2D echocardiography done using an EPIQ 7 premium ultrasound system (Philips Healthcare, Stockholm, Sweden) equipped with a 2.5-MHz transducer. All measurements were performed following the recommendations of the American Society of Echocardiography (21)in apical (2- and 4-chamber and apical long axis) and parasternal (long and short axis) views and measured at the time of acquisition without reference to previous measurements. Images was digitally stored for off-line Speckle-tracking analysis (EchoPAC 108.1.5, GE-Vingmed). Longitudinal strain, evaluating the shortening (negative strain) and lengthening (positive strain) of the myocardial wall, was measured from the three apical views (long-axis and two- and four-chamber views): GLS was calculated by averaging the peak strain values of 18 segments. The mean frame rate of 2D images was 90 ±4 frames/s.

SPSS version 18.0 (SPSS, Inc., Chicago, IL) was used for statistical analysis. All quantitative data have been expressed as mean ± SD.Categorical variables were summarized as number(percent), and continuous variables as either median (range) or mean ± standard deviation. Independent-sample t-tests were used to compare LVEF, strain and strain-rate parameters between the two groups before and after the intervention. Paired sample t-tests were used to compare the echocardiography findings in each group before and after the chemotherapy. P-values less than 0.05 were considered to be statistically significant.

Conditions

Cardiomyopathies; Chemotherapy Effect; Diastolic Dysfunction; Systolic Dysfunction

Study Design

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

Study Groups

Bisoprolol

40 patients who were given bisoprolol at a dose of 1.25 mg daily, and in the absence of clinical symptoms and heart rate above 60 and systolic blood pressure above 100, 1.25 mg was added to the therapeutic dose every 2 weeks to reach 5 mg daily.

Group Type: EXPERIMENTAL

Bisoprolol

Intervention Type: DRUG

For patients who were candidates to start therapy with anthracycline, bisoprolol was administrated as explained before to determine the effect of this drug on the reduction of anthracycline-induced cardiomyopathy.

Placebo

Two placebo tablets in similar shape and color to bisoprolol were given on a daily basis to each of the 40patients as the control group.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablets with similar shape and size and color to bisoprolol were given to the patients whom undergone chemotherapy with anthracyclines to compare the effects between two groups.

Interventions

Bisoprolol

For patients who were candidates to start therapy with anthracycline, bisoprolol was administrated as explained before to determine the effect of this drug on the reduction of anthracycline-induced cardiomyopathy.

Intervention Type: DRUG

Placebo

Tablets with similar shape and size and color to bisoprolol were given to the patients whom undergone chemotherapy with anthracyclines to compare the effects between two groups.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

patients that was diagnosed with non-metastatic breast cancer and anthracycline-based chemotherapy were planned for them

Exclusion Criteria

• Established ischemic heart disease
• Baseline LVEF <50%, cardiomyopathy (restrictive, dilated or hypertrophic) detected by transthoracic echocardiography
• Moderate or severe valvular disease,
• Prior chemotherapy,
• Presence of contraindication for beta-blockers and cardiac arrhythmias and lack of patient compliance
• Patients that had consuming angiotensin converting enzyme Inhibitors, angiotensin receptor Inhibitors,diuretics,statins,other beta-blockers or non-dihydropyridin calcium channel blockers

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Shahid Beheshti University of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Manoochehr Ebrahimian

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Rasool Akram hospital

Tehran, , Iran

Countries

Iran

References

Tashakori Beheshti A, Mostafavi Toroghi H, Hosseini G, Zarifian A, Homaei Shandiz F, Fazlinezhad A. Carvedilol Administration Can Prevent Doxorubicin-Induced Cardiotoxicity: A Double-Blind Randomized Trial. Cardiology. 2016;134(1):47-53. doi: 10.1159/000442722. Epub 2016 Feb 12.

Reference Type: BACKGROUND

PMID: 26866364 (View on PubMed)

Silber JH, Cnaan A, Clark BJ, Paridon SM, Chin AJ, Rychik J, Hogarty AN, Cohen MI, Barber G, Rutkowski M, Kimball TR, Delaat C, Steinherz LJ, Zhao H. Enalapril to prevent cardiac function decline in long-term survivors of pediatric cancer exposed to anthracyclines. J Clin Oncol. 2004 Mar 1;22(5):820-8. doi: 10.1200/JCO.2004.06.022.

Reference Type: BACKGROUND

PMID: 14990637 (View on PubMed)

Other Identifiers

SamanRostambeigi

Identifier Type: -

Identifier Source: org_study_id