- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05175066
Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
Can Bisoprolol Administration Prevent Anthracycline-induced Cardiotoxicity?: a Double-blind Randomized Trial.
Study Overview
Status
Intervention / 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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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-
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Tehran, Iran, Islamic Republic of, 1995614331
- Rasool Akram hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
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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.
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Placebo Comparator: 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.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
LVEF
Time Frame: Baseline and after 6 months
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Change in Left ventricular ejection-fraction after chemotherapy
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Baseline and after 6 months
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GLS
Time Frame: Baseline and after 6 months
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Change in global longitudinal strain after chemotherapy
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Baseline and after 6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Diastolic dysfunction
Time Frame: Baseline and after 6 months
|
Occurrence of diastolic dysfunction after chemotherapy
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Baseline and after 6 months
|
Collaborators and Investigators
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Pathologic Processes
- Heart Diseases
- Cardiovascular Diseases
- Wounds and Injuries
- Drug-Related Side Effects and Adverse Reactions
- Radiation Injuries
- Cardiomyopathies
- Cardiotoxicity
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Antihypertensive Agents
- Autonomic Agents
- Peripheral Nervous System Agents
- Sympatholytics
- Adrenergic beta-1 Receptor Antagonists
- Bisoprolol
Other Study ID Numbers
- SamanRostambeigi
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
- Analytic Code
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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