CardiotoxicityANTIOX-10NCT07680855
ANTthracycline-induced Inflammation and OXidative Stress: 10-year Follow-up
An observational study of Cardiotoxicity and Anthracycline Related Cardiotoxicity in Breast Cancer, run by University of Chile.
Trial summary
The goal of this observational study is to learn about the long-term effects of anthracycline chemotherapy on inflammation, oxidative stress, and heart function in adult women with breast cancer. The main questions it aims to answer are: 1. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Cardiotoxicity, Anthracycline Related Cardiotoxicity in Breast Cancer, Breast Cancer
- How many people
- 17 participants
- Where
- No sites listed yet
- Study dates
- 1 Feb 2011to Apr 2026
- How long will I take part?
- 10 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Adult women with breast cancer treated at Hospital del Salvador, Santiago, Chile. Patients were consecutively recruited between 2010 and 2013 from a prospective cohort of individuals initiating anthracycline-based chemotherapy. A protocol amendment approved by the local ethics committee allowed long-term follow-up of the original cohort at 10 years for cardiovascular, inflammatory, and oxidative stress assessment.
Who may be able to join
- Female patients with histologically confirmed breast cancer
- Age between 18 and 75 years
- Indication for anthracycline-based chemotherapy (>200 mg/m²)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Written informed consent signed prior to study participation
- Availability for baseline cardiovascular and biomarker assessment and long-term follow-up
Who cannot join
- History of heart failure or left ventricular dysfunction (LVEF <53%)
- Known coronary artery disease or clinically significant ischemic heart disease
- History of clinically significant arrhythmias or requirement for antiarrhythmic therapy
- Dilated or hypertrophic cardiomyopathy
- Moderate to severe valvular heart disease (mitral or aortic stenosis or regurgitation)
- Congenital heart disease (including atrial or ventricular septal defects, patent ductus arteriosus, Ebstein anomaly, tetralogy of Fallot, coarctation of the aorta)
- Chronic kidney disease (creatinine >2 mg/dL)
- Hepatic failure (bilirubin >3 mg/dL, albumin <3.5 g/dL, or prothrombin activity <60% in absence of anticoagulation)
About this study
Official title: Long-Term Effects of Anthracycline Chemotherapy on Inflammatory Cytokines, Redox Status, and Ventricular Function in Breast Cancer Survivors
The goal of this observational study is to learn about the long-term effects of anthracycline chemotherapy on inflammation, oxidative stress, and heart function in adult women with breast cancer.
The main questions it aims to answer are:
Read more
- Do inflammatory cytokine levels change after anthracycline chemotherapy and remain altered many years after treatment?
- Are long-term markers of oxidative stress and antioxidant capacity associated with changes in heart structure or function after anthracycline exposure?
This study does not include a comparison group. All participants were previously treated with anthracycline-based chemotherapy as part of their standard cancer care.
Participants will:
- Provide blood samples for the measurement of inflammatory cytokines and oxidative stress-related biomarkers
- Undergo a clinical cardiovascular evaluation
- Receive a transthoracic echocardiogram to assess heart function, including measures of systolic and diastolic function and myocardial deformation
- Participate in a long-term follow-up assessment approximately 10 years after their initial cancer treatment
Read the detailed description
- Study design and population. This is a prospective, observational translational study including adult patients with breast cancer undergoing anthracycline-based chemotherapy at a single tertiary-care center. Patients are evaluated longitudinally to assess subclinical cardiovascular alterations associated with anthracycline exposure. All participants are managed according to standard oncologic and cardiologic care pathways.
- Echocardiographic assessment. Transthoracic echocardiography is performed by experienced cardiologists following current American Society of Echocardiography (ASE) recommendations. Studies are acquired at predefined time points, including baseline (prior to anthracycline exposure) and long-term follow-up. Left ventricular systolic function is assessed using biplane left ventricular ejection fraction (LVEF) calculated by the modified Simpson method. Diastolic function parameters include transmitral inflow velocities, tissue Doppler-derived mitral annular velocities, E/e' ratio, and left atrial volume index (LAVI). Left ventricular global longitudinal strain (GLS) is assessed at long-term follow-up using semi-automated speckle-tracking techniques. Right ventricular-pulmonary artery coupling is explored using the Tricuspid Annular Plane Systolic Excursion (TAPSE)/Pulmonary Artery Systolic Pressure (PASP) ratio. All measurements are performed offline, and segments with inadequate image quality are excluded from analysis.
- Blood sample collection and processing. Peripheral venous blood samples are collected under standardized conditions at baseline (pre-anthracycline), early after chemotherapy exposure, and at long-term follow-up. Samples are obtained using chilled anticoagulant-containing tubes, centrifuged according to protocol, aliquoted, and stored at -80 °C until biochemical analyses are performed. All samples are processed under identical experimental conditions to minimize analytical variability.
- Oxidative stress and antioxidant parameters. Plasma antioxidant capacity is assessed using the Ferric Reducing Ability of Plasma (FRAP) assay at predefined time points. Activities of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, are determined in erythrocyte lysates using commercially available assay kits according to manufacturers' instructions. Lipid peroxidation and intracellular redox status are evaluated using established biochemical methods. Results are normalized to protein concentration when applicable.
- Inflammatory and proinflammatory cytokines. Circulating cytokines and growth factors are quantified in plasma samples using multiplex bead-based immunoassays. Measurements are performed at baseline and early after anthracycline exposure following standardized manufacturer protocols. Analyte concentrations are calculated based on standard curves generated for each biomarker.
- Data integration and quality control. Clinical, echocardiographic, and biochemical data are collected using predefined case report forms. Data quality is ensured through consistency checks and verification procedures. All laboratory analyses and imaging measurements are performed blinded to clinical outcomes.
- Exploratory analyses Echocardiographic parameters are integrated with biochemical markers of oxidative stress and inflammation for exploratory mechanistic analyses aimed at identifying associations between myocardial deformation indices and biological signatures of anthracycline-related cardiotoxicity.
- Keywords
- Cardio-oncology, Anthracycline chemotherapy, Echocardiography, Global longitudinal strain, Oxidative stress, Antioxidant capacity, Inflammatory cytokines, Subclinical cardiotoxicity, Long-term follow-up, Breast cancer survivors
- Medical subject headings
- Cardiotoxicity, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Long-term anthracycline breast cancer cohort | Women with histologically confirmed breast cancer who received anthracycline-based chemotherapy (>200 mg/m²) between 2010 and 2013 at Hospital Salvador, Santiago, Chile. This cohort was followed longitudinally from baseline pre-chemotherapy assessment and reassessed after 10 years. The study is observational and no therapeutic intervention was assigned as part of the protocol. Serial evaluations included echocardiographic parameters, inflammatory cytokines, oxidative stress biomarkers, and cardiac remodeling indicators. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in left ventricular ejection fraction from baseline to 10-year follow-up
Assessment of left ventricular systolic function by biplane Simpson method using transthoracic echocardiography. Left ventricular ejection fraction (LVEF) was measured at baseline (7 days before the first cycle of anthracycline chemotherapy) and at the 10-year follow-up.
Measured: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
Change in left ventricular filling pressure (E/e' ratio) from baseline to 10-year follow-up
Assessment of left ventricular diastolic function using the average E/e' ratio obtained by transthoracic echocardiography. Measurements were performed at baseline (7 days before the first cycle of anthracycline chemotherapy) and at the 10-year follow-up.
Measured: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
Secondary outcomes (7)
Left ventricular global longitudinal strain at 10-year follow-up
Assessment of left ventricular global longitudinal strain (LVGLS) using speckle-tracking echocardiography at the 10-year follow-up. Baseline LVGLS measurements were not available; therefore, only long-term values were assessed.
Measured: 10 years after completion of chemotherapy
Left atrial volume index at 10-year follow-up
Assessment of left atrial volume index (LAVI) by transthoracic echocardiography as an indicator of long-term left atrial remodeling after anthracycline exposure.
Measured: 10 years after completion of chemotherapy
Right ventricular-pulmonary arterial coupling (TAPSE/PASP ratio) at 10-year follow-up
Assessment of right ventricular-pulmonary arterial coupling using the tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio obtained by transthoracic echocardiography.
Measured: 10 years after completion of chemotherapy
Plasma antioxidant capacity measured by ferric reducing ability of plasma assay
Assessment of systemic antioxidant capacity using the ferric reducing ability of plasma (FRAP) assay. Plasma samples were obtained at baseline (7 days before the first anthracycline chemotherapy cycle), on day 3 after the first chemotherapy cycle , and at the 10-year follow-up.
Measured: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Erythrocyte antioxidant enzyme activity
Assessment of erythrocyte antioxidant enzyme activity by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities using standardized commercial assays. These enzymes were evaluated as complementary indicators of endogenous antioxidant defense mechanisms.
Measured: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Markers of oxidative stress and intracellular redox status
Assessment of oxidative stress by measuring plasma 8-isoprostane concentrations and intracellular redox status using the reduced-to-oxidized glutathione (GSH/GSSG) ratio.
Measured: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Inflammatory cytokine profile measured by multiplex immunoassay
Assessment of the systemic inflammatory cytokine profile using a validated MILLIPLEX® multiplex bead-based immunoassay based on Luminex® xMAP® technology. Plasma cytokines were measured simultaneously as a single multiplex biomarker panel comprising inflammatory cytokines and chemokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), and additional analytes included in the assay. This outcome represents the overall inflammatory biomarker profile generated by a single multiplex assay rather than multiple independent outcome measures.
Measured: Baseline (7 days before the first anthracycline chemotherapy cycle), and day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2026
- Study start1 Feb 2011
- Primary completionApr 2026
- Study completionApr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CardiotoxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 17 participants (actual)
- Target duration
- 10 Years
Sponsor and investigators
- Lead sponsor
- University of Chile
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, RODRIGO CASTILLO, University of Chile
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07680855
- Sponsor's protocol ID
- CEC-SSMO-97-2021
- Acronym
- ANTIOX-10
- Status last verified
- Jun 2026
- First submitted
- 15 Jun 2026
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-Term Effects of Anthracycline Chemotherapy on Inflammatory Cytokines, Redox Status, and Ventricular Function in Breast Cancer Survivors
- ClinicalTrials.gov ID
- NCT07680855
- Acronym / sponsor ID
- ANTIOX-10 / CEC-SSMO-97-2021
- Keywords
- Cardio-oncology, Anthracycline chemotherapy, Echocardiography, Global longitudinal strain, Oxidative stress, Antioxidant capacity, Inflammatory cytokines, Subclinical cardiotoxicity
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of ChileUniversity, hospital or other
- Study start
- 1 Feb 2011 (actual)
- Primary completion
- Apr 2026 (actual)
- Study completion
- Apr 2026 (actual)
- First posted
- 2 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this observational study is to learn about the long-term effects of anthracycline chemotherapy on inflammation, oxidative stress, and heart function in adult women with breast cancer.
The main questions it aims to answer are:
- Do inflammatory cytokine levels change after anthracycline chemotherapy and remain altered many years after treatment?
- Are long-term markers of oxidative stress and antioxidant capacity associated with changes in heart structure or function after anthracycline exposure?
This study does not include a comparison group. All participants were previously treated with anthracycline-based chemotherapy as part of their standard cancer care.
Participants will:
- Provide blood samples for the measurement of inflammatory cytokines and oxidative stress-related biomarkers
- Undergo a clinical cardiovascular evaluation
- Receive a transthoracic echocardiogram to assess heart function, including measures of systolic and diastolic function and myocardial deformation
- Participate in a long-term follow-up assessment approximately 10 years after their initial cancer treatment
Detailed description
- Study design and population. This is a prospective, observational translational study including adult patients with breast cancer undergoing anthracycline-based chemotherapy at a single tertiary-care center. Patients are evaluated longitudinally to assess subclinical cardiovascular alterations associated with anthracycline exposure. All participants are managed according to standard oncologic and cardiologic care pathways.
- Echocardiographic assessment. Transthoracic echocardiography is performed by experienced cardiologists following current American Society of Echocardiography (ASE) recommendations. Studies are acquired at predefined time points, including baseline (prior to anthracycline exposure) and long-term follow-up. Left ventricular systolic function is assessed using biplane left ventricular ejection fraction (LVEF) calculated by the modified Simpson method. Diastolic function parameters include transmitral inflow velocities, tissue Doppler-derived mitral annular velocities, E/e' ratio, and left atrial volume index (LAVI). Left ventricular global longitudinal strain (GLS) is assessed at long-term follow-up using semi-automated speckle-tracking techniques. Right ventricular-pulmonary artery coupling is explored using the Tricuspid Annular Plane Systolic Excursion (TAPSE)/Pulmonary Artery Systolic Pressure (PASP) ratio. All measurements are performed offline, and segments with inadequate image quality are excluded from analysis.
- Blood sample collection and processing. Peripheral venous blood samples are collected under standardized conditions at baseline (pre-anthracycline), early after chemotherapy exposure, and at long-term follow-up. Samples are obtained using chilled anticoagulant-containing tubes, centrifuged according to protocol, aliquoted, and stored at -80 °C until biochemical analyses are performed. All samples are processed under identical experimental conditions to minimize analytical variability.
- Oxidative stress and antioxidant parameters. Plasma antioxidant capacity is assessed using the Ferric Reducing Ability of Plasma (FRAP) assay at predefined time points. Activities of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, are determined in erythrocyte lysates using commercially available assay kits according to manufacturers' instructions. Lipid peroxidation and intracellular redox status are evaluated using established biochemical methods. Results are normalized to protein concentration when applicable.
- Inflammatory and proinflammatory cytokines. Circulating cytokines and growth factors are quantified in plasma samples using multiplex bead-based immunoassays. Measurements are performed at baseline and early after anthracycline exposure following standardized manufacturer protocols. Analyte concentrations are calculated based on standard curves generated for each biomarker.
- Data integration and quality control. Clinical, echocardiographic, and biochemical data are collected using predefined case report forms. Data quality is ensured through consistency checks and verification procedures. All laboratory analyses and imaging measurements are performed blinded to clinical outcomes.
- Exploratory analyses Echocardiographic parameters are integrated with biochemical markers of oxidative stress and inflammation for exploratory mechanistic analyses aimed at identifying associations between myocardial deformation indices and biological signatures of anthracycline-related cardiotoxicity.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 10 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Long-term anthracycline breast cancer cohort | – | –Women with histologically confirmed breast cancer who received anthracycline-based chemotherapy (>200 mg/m²) between 2010 and 2013 at Hospital Salvador, Santiago, Chile. This cohort was followed longitudinally from baseline pre-chemotherapy assessment and reassessed after 10 years. The study is observational and no therapeutic intervention was assigned as part of the protocol. Serial evaluations included echocardiographic parameters, inflammatory cytokines, oxidative stress biomarkers, and cardiac remodeling indicators. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult women with breast cancer treated at Hospital del Salvador, Santiago, Chile. Patients were consecutively recruited between 2010 and 2013 from a prospective cohort of individuals initiating anthracycline-based chemotherapy. A protocol amendment approved by the local ethics committee allowed long-term follow-up of the original cohort at 10 years for cardiovascular, inflammatory, and oxidative stress assessment.
Key inclusion criteria (6 listed)
- Female patients with histologically confirmed breast cancer
- Age between 18 and 75 years
- Indication for anthracycline-based chemotherapy (>200 mg/m²)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Written informed consent signed prior to study participation
Key exclusion criteria (8 listed)
- History of heart failure or left ventricular dysfunction (LVEF <53%)
- Known coronary artery disease or clinically significant ischemic heart disease
- History of clinically significant arrhythmias or requirement for antiarrhythmic therapy
- Dilated or hypertrophic cardiomyopathy
- Moderate to severe valvular heart disease (mitral or aortic stenosis or regurgitation)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in left ventricular ejection fraction from baseline to 10-year follow-up
Time frame: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
Assessment of left ventricular systolic function by biplane Simpson method using transthoracic echocardiography. Left ventricular ejection fraction (LVEF) was measured at baseline (7 days before the first cycle of anthracycline chemotherapy) and at the 10-year follow-up.
Change in left ventricular filling pressure (E/e' ratio) from baseline to 10-year follow-up
Time frame: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy
Assessment of left ventricular diastolic function using the average E/e' ratio obtained by transthoracic echocardiography. Measurements were performed at baseline (7 days before the first cycle of anthracycline chemotherapy) and at the 10-year follow-up.
7 secondary outcomes
Left ventricular global longitudinal strain at 10-year follow-up
Time frame: 10 years after completion of chemotherapy
Left atrial volume index at 10-year follow-up
Time frame: 10 years after completion of chemotherapy
Right ventricular-pulmonary arterial coupling (TAPSE/PASP ratio) at 10-year follow-up
Time frame: 10 years after completion of chemotherapy
Plasma antioxidant capacity measured by ferric reducing ability of plasma assay
Time frame: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Erythrocyte antioxidant enzyme activity
Time frame: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Markers of oxidative stress and intracellular redox status
Time frame: Baseline (7 days before the first anthracycline chemotherapy cycle), day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days), and 10 years after completion of chemotherapy.
Inflammatory cytokine profile measured by multiplex immunoassay
Time frame: Baseline (7 days before the first anthracycline chemotherapy cycle), and day 3 after the first anthracycline chemotherapy cycle (cycle length: 21 days).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiotoxicity and Anthracycline Related Cardiotoxicity in Breast Cancer, run by University of Chile.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in left ventricular ejection fraction from baseline to 10-year follow-up (time frame: From baseline (7 days before the first anthracycline chemotherapy cycle) to 10 years after completion of chemotherapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.