Anthracycline Induced CardiotoxicityNCT04852965
Late Anthracycline Induced Cardiotoxicity- Childhood Cancer Survivors
An observational study of Anthracycline Induced Cardiotoxicity, run by Queen's University, Belfast at 1 site in United Kingdom.
Trial summary
Anthracyclines treat up to 60% of childhood malignancies with remarkable improvements survival rates. Unfortunately anthracyclines are associated with an increased cardiomyopathy risk. One study showed an almost six-fold greater risk of developing cardiomyopathy compared to sibling controls. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anthracycline Induced Cardiotoxicity
- How many people
- 103 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Oct 2021to 15 Apr 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult patients identified by paediatric oncology who have received anthracycline therapy in childhood.
Who may be able to join
- -Male and female patients over the age of 18 who have received at least moderate (100mg/m2) anthracycline chemotherapy as a child (<16 years).
Who cannot join
- patients born with complex heart disease
- patients who would not be safely able to have a magnetic resonance imaging scan
- patients who cannot give consent
- patients under the age of 18 or who have had less than a moderate dose of anthracycline
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Belfast Health and Social Care Trust
Belfast, BT9 7AB
About this study
Official title: Early Detection of Late Anthracycline Induced Cardiotoxicity in Survivors of Childhood Malignancy
Anthracyclines treat up to 60% of childhood malignancies with remarkable improvements survival rates. Unfortunately anthracyclines are associated with an increased cardiomyopathy risk. One study showed an almost six-fold greater risk of developing cardiomyopathy compared to sibling controls. A retrospective pilot study showed evidence of subclinical dysfunction (including impaired global longitudinal strain) in 42/52 childhood cancer survivors. There is limited research in this area, therefore current guidelines are based on expert opinion alone and lack consensus. Current methods of detection diagnose cardiomyopathy at an irreversible stage i.e. when the compensatory mechanisms are exhausted and the left ventricular ejection fraction impaired. Small trials have shown that early treatment with standard heart failure therapy may reverse damage, further validation is however required in this cohort.
Newer techniques such as tissue doppler and strain rate imaging have shown promise for early prediction of cardiomyopathy in adult studies. Biomarkers such as troponin and NT-proBNP have also shown a correlation with cardiomyopathy.
Read more
This study (n=208) aims to use echocardiography, strain imaging, holter monitoring and MRI for early detection of cardiomyopathy. Biomarkers, both currently used (for example, troponin and NTproBNP,) and more novel (for example, IL6, MPO, and sST2) will be assessed to see if early cardiomyopathy can be predicted.
This study will explore biomarker discovery by analysing an age/gender matched subgroup for the top differentially expressed microRNA and protein biomarkers. Selected biomarkers will then be validated in a larger cohort.
Read the detailed description
CLINICAL APPOINTMENT A linked anonymised Case Report Form will be completed using participant answers and relevant aspects of their electronic care record. This will involve questions about the patient's demographics, chemotherapy history, cardiac symptoms, past medical history, medication history and family history.
Consenting patients will then have
- height, weight and blood pressure taken
- cardiovascular and respiratory examination Participants will then undergo
- SF36 quality of life questionnaire
- 6 minute walk test, grip strength
- Electrocardiogram by a trained researcher
- Venesection- 40ml blood sample from a peripheral vein by the trained researcher Crevicular fluid sample
INVESTIGATIONS
Participants will be invited for:
- 24 hour holter monitor- arrhythmia assessment
- Echocardiogram- diastolic and systolic function assessment, valvular analysis, global longitudinal strain
- Magnetic resonance imaging (MRI) scan of the heart- volumetric analysis, late gadolinium enhancement and STIR imaging assessments. As part of the scan the patient will require a venflon to be inserted into a peripheral vein for gadolinium injection. A safety questionnaire will be sent to the patient prior to attendance as part of standard MRI procedure. All safety aspects will be re-assessed on the day of attendance by a trained radiographer
BLOOD SAMPLE ANALYSIS Blood samples will be sent for standard of care and cardiovascular risk assessment. Tests include a full blood picture, urea and electrolytes, C-reactive protein, iron profile, B12 and folate, lipid profile, HbA1c, NT-proBNP and high sensitivity troponin.
Additional disease associated biomarkers for example sST2, MPO, and IL6 will be quantified using immunoassays. Biomarker discovery, including transcriptomics and proteomics will be carried out to identify signatures that could predict cardiotoxicity, subclinical dysfunction, and cardiomyopathy.
- Conditions
- Anthracycline Induced Cardiotoxicity
- Keywords
- Anthracycline, Doxorubicin, Cardiotoxicity, Strain, IL6, sST2, MPO, Cardiomyopathy, Transcriptomics, MRI, Echocardiography, Cardio-oncology, Proteomics
- Medical subject headings
- Cardiotoxicity, Sprains and Strains, Cardiomyopathies
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiotoxicity
Number of participants with anthracycline related cardiotoxicity as defined by the British Society of Echocardiography and British Cardio-Oncology Society guidelines
Measured: 2 years
Secondary outcomes (1)
Incidence of myocardial injury
Levels of high sensitivity troponin T and NT-proBNP
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2021
- Study start20 Oct 2021
- Primary completion15 Apr 2024
- Study completion15 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Anthracycline Induced 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
- Cross-sectional
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen's University, Belfast
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chris Watson, Queen's University, Belfast
- Investigators
- Lana J Dixon, MB BCh BAO, Principal investigator, National Health Service, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04852965
- Sponsor's protocol ID
- B21/01
- Status last verified
- Aug 2026
- First submitted
- 1 Apr 2021
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Thompson KA. Pregnancy and Cardiomyopathy After Anthracyclines in Childhood. Front Cardiovasc Med. 2018 Mar 26;5:14. doi: 10.3389/fcvm.2018.00014. eCollection 2018.
PubMed 29632865Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, Donaldson SS, Green DM, Sklar CA, Robison LL, Leisenring WM. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ. 2009 Dec 8;339:b4606. doi: 10.1136/bmj.b4606.
PubMed 19996459Curigliano G, Cardinale D, Suter T, Plataniotis G, de Azambuja E, Sandri MT, Criscitiello C, Goldhirsch A, Cipolla C, Roila F; ESMO Guidelines Working Group. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012 Oct;23 Suppl 7:vii155-66. doi: 10.1093/annonc/mds293.
PubMed 22997448Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, Rubino M, Veglia F, Fiorentini C, Cipolla CM. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010 Jan 19;55(3):213-20. doi: 10.1016/j.jacc.2009.03.095.
PubMed 20117401Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012 Sep 1;5(5):596-603. doi: 10.1161/CIRCIMAGING.112.973321. Epub 2012 Jun 28.
PubMed 22744937Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, Civelli M, Peccatori F, Martinelli G, Fiorentini C, Cipolla CM. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004 Jun 8;109(22):2749-54. doi: 10.1161/01.CIR.0000130926.51766.CC. Epub 2004 May 17.
PubMed 15148277Romano S, Fratini S, Ricevuto E, Procaccini V, Stifano G, Mancini M, Di Mauro M, Ficorella C, Penco M. Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients. Br J Cancer. 2011 Nov 22;105(11):1663-8. doi: 10.1038/bjc.2011.439. Epub 2011 Nov 8.
PubMed 22068815
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Late Anthracycline Induced Cardiotoxicity in Survivors of Childhood Malignancy
- ClinicalTrials.gov ID
- NCT04852965
- Acronym / sponsor ID
- B21/01
- Conditions
- Anthracycline Induced Cardiotoxicity
- Keywords
- Anthracycline, Doxorubicin, Cardiotoxicity, Strain, IL6, sST2, MPO, Cardiomyopathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Queen's University, BelfastUniversity, hospital or other
- Study start
- 20 Oct 2021 (actual)
- Primary completion
- 15 Apr 2024 (actual)
- Study completion
- 15 Apr 2024 (actual)
- First posted
- 21 Apr 2021 (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.
Anthracyclines treat up to 60% of childhood malignancies with remarkable improvements survival rates. Unfortunately anthracyclines are associated with an increased cardiomyopathy risk. One study showed an almost six-fold greater risk of developing cardiomyopathy compared to sibling controls. A retrospective pilot study showed evidence of subclinical dysfunction (including impaired global longitudinal strain) in 42/52 childhood cancer survivors. There is limited research in this area, therefore current guidelines are based on expert opinion alone and lack consensus. Current methods of detection diagnose cardiomyopathy at an irreversible stage i.e. when the compensatory mechanisms are exhausted and the left ventricular ejection fraction impaired. Small trials have shown that early treatment with standard heart failure therapy may reverse damage, further validation is however required in this cohort.
Newer techniques such as tissue doppler and strain rate imaging have shown promise for early prediction of cardiomyopathy in adult studies. Biomarkers such as troponin and NT-proBNP have also shown a correlation with cardiomyopathy.
This study (n=208) aims to use echocardiography, strain imaging, holter monitoring and MRI for early detection of cardiomyopathy. Biomarkers, both currently used (for example, troponin and NTproBNP,) and more novel (for example, IL6, MPO, and sST2) will be assessed to see if early cardiomyopathy can be predicted.
This study will explore biomarker discovery by analysing an age/gender matched subgroup for the top differentially expressed microRNA and protein biomarkers. Selected biomarkers will then be validated in a larger cohort.
Detailed description
CLINICAL APPOINTMENT A linked anonymised Case Report Form will be completed using participant answers and relevant aspects of their electronic care record. This will involve questions about the patient's demographics, chemotherapy history, cardiac symptoms, past medical history, medication history and family history.
Consenting patients will then have
- height, weight and blood pressure taken
- cardiovascular and respiratory examination Participants will then undergo
- SF36 quality of life questionnaire
- 6 minute walk test, grip strength
- Electrocardiogram by a trained researcher
- Venesection- 40ml blood sample from a peripheral vein by the trained researcher Crevicular fluid sample
INVESTIGATIONS
Participants will be invited for:
- 24 hour holter monitor- arrhythmia assessment
- Echocardiogram- diastolic and systolic function assessment, valvular analysis, global longitudinal strain
- Magnetic resonance imaging (MRI) scan of the heart- volumetric analysis, late gadolinium enhancement and STIR imaging assessments. As part of the scan the patient will require a venflon to be inserted into a peripheral vein for gadolinium injection. A safety questionnaire will be sent to the patient prior to attendance as part of standard MRI procedure. All safety aspects will be re-assessed on the day of attendance by a trained radiographer
BLOOD SAMPLE ANALYSIS Blood samples will be sent for standard of care and cardiovascular risk assessment. Tests include a full blood picture, urea and electrolytes, C-reactive protein, iron profile, B12 and folate, lipid profile, HbA1c, NT-proBNP and high sensitivity troponin.
Additional disease associated biomarkers for example sST2, MPO, and IL6 will be quantified using immunoassays. Biomarker discovery, including transcriptomics and proteomics will be carried out to identify signatures that could predict cardiotoxicity, subclinical dysfunction, and cardiomyopathy.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult patients identified by paediatric oncology who have received anthracycline therapy in childhood.
Key inclusion criteria (1 listed)
- -Male and female patients over the age of 18 who have received at least moderate (100mg/m2) anthracycline chemotherapy as a child (<16 years).
Key exclusion criteria (4 listed)
- patients born with complex heart disease
- patients who would not be safely able to have a magnetic resonance imaging scan
- patients who cannot give consent
- patients under the age of 18 or who have had less than a moderate dose of anthracycline
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
Cardiotoxicity
Time frame: 2 years
Number of participants with anthracycline related cardiotoxicity as defined by the British Society of Echocardiography and British Cardio-Oncology Society guidelines
1 secondary outcome
Incidence of myocardial injury
Time frame: 2 years
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 12 Aug 2026.
- Background: PubMed 29632865Thompson KA. Pregnancy and Cardiomyopathy After Anthracyclines in Childhood. Front Cardiovasc Med. 2018 Mar 26;5:14. doi: 10.3389/fcvm.2018.00014. eCollection 2018.
- Background: PubMed 19996459Mulrooney DA, Yeazel MW, Kawashima T, Mertens AC, Mitby P, Stovall M, Donaldson SS, Green DM, Sklar CA, Robison LL, Leisenring WM. Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. BMJ. 2009 Dec 8;339:b4606. doi: 10.1136/bmj.b4606.
- Background: PubMed 22997448Curigliano G, Cardinale D, Suter T, Plataniotis G, de Azambuja E, Sandri MT, Criscitiello C, Goldhirsch A, Cipolla C, Roila F; ESMO Guidelines Working Group. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012 Oct;23 Suppl 7:vii155-66. doi: 10.1093/annonc/mds293.
- Background: PubMed 20117401Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, De Giacomi G, Rubino M, Veglia F, Fiorentini C, Cipolla CM. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010 Jan 19;55(3):213-20. doi: 10.1016/j.jacc.2009.03.095.
- Background: PubMed 22744937Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Tan TC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012 Sep 1;5(5):596-603. doi: 10.1161/CIRCIMAGING.112.973321. Epub 2012 Jun 28.
- Background: PubMed 15148277Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M, Lamantia G, Civelli M, Peccatori F, Martinelli G, Fiorentini C, Cipolla CM. Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation. 2004 Jun 8;109(22):2749-54. doi: 10.1161/01.CIR.0000130926.51766.CC. Epub 2004 May 17.
- Background: PubMed 22068815Romano S, Fratini S, Ricevuto E, Procaccini V, Stifano G, Mancini M, Di Mauro M, Ficorella C, Penco M. Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients. Br J Cancer. 2011 Nov 22;105(11):1663-8. doi: 10.1038/bjc.2011.439. Epub 2011 Nov 8.
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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.
Lana J Dixon, MB BCh BAO principal investigator
National Health Service, United Kingdom
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anthracycline Induced Cardiotoxicity, run by Queen's University, Belfast at 1 site in United Kingdom.
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 1 inclusion and 4 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 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Cardiotoxicity (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04852965, which also lists 7 linked publications.
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 12 Aug 2026.