Cardiac side effects of chemotherapy with anthracyclines in sarcoma patients assessed by cardiac MRI

ISRCTN ISRCTN12210850
DOI https://doi.org/10.1186/ISRCTN12210850
Secondary identifying numbers CARETOX-1
Submission date
14/07/2017
Registration date
11/08/2017
Last edited
29/01/2020
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Injury, Occupational Diseases, Poisoning
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
It has been known since the 1970s that chemotherapy with anthracyclines can have adverse side effects on heart function. Between 5 and 30% of all patients treated with anthracyclines develop a decrease in heart function. Nevertheless, anthracyclines play a pivotal role in the treatment of many cancers, such as breast cancers and cancer of the connective tissue (sarcomas). With the fortunate development of increasing numbers of cancer survivors the long-term side effects of chemotherapy become more and more important. The current strategy of assessment of patients for development of heart failure under chemotherapy is mainly based on close observation using ultrasound. There is currently no reliable tool for predicting heart failure under chemotherapy before it actually occurs, or tools for identifying patients at highest risk. MRI is the gold standard for assessment of heart function and has the unique ability to also assess changes in the heart muscle which are known to predict the development of subsequent heart failure. It is thought that chemotherapy with anthracyclines leads to very early changes in the tissue of the heart muscle. These changes may be detectable by MRI and may help to predict the development of heart failure at a much later point in time. Hence, the aim of this study is to assess changes in the heart tissue before and very early (24-48 hours) after the first treatment with anthracyclines using MRI and compare these changes to the development of heart function at the end of chemotherapy treatment (usually after 4-5 months) also assessed by MRI.

Who can participate?
Patients aged at least 18 with sarcoma undergoing chemotherapy with anthracyclines

What does the study involve?
All patients receive three standard MRI scans - one scan before the start of chemotherapy, one 24-48 hours after the first treatment and one 3-4 weeks after the end of chemotherapy. The first and the last MRI scan are part of a normal exam and only the second MRI scan is performed merely due to study participation. Participants also provide blood samples and their heart electrical activity is recorded (electrocardiography [ECG]) at the time of each MRI scan.

What are the benefits and risk of participating?
Benefits include a closer observation of heart function through participation in this study. Extraordinary findings are reported to the referring doctors. One of the three MRI scans is additional and merely performed due to study participation. Since the other two MRI scans are performed anyway, there is no additional burden from a patient's perspective besides the single additional MRI exam.

Where is the study run from?
HELIOS Clinic Berlin-Buch (Germany)

When is the study starting and how long is it expected to run for?
October 2014 to December 2016

Who is funding the study?
1. Charité Universitätsmedizin Berlin (Germany)
2. HELIOS Kliniken (Germany)

Who is the main contact?
Prof. Jeanette Schulz-Menger

Contact information

Prof Jeanette Schulz-Menger
Scientific

Charité University Medicine Berlin
Campus Buch
Working group Kardiale MRT
Lindenberger Weg 80
Berlin
13125
Germany

Study information

Study designObservational cohort study
Primary study designObservational
Secondary study designCohort study
Study setting(s)Hospital
Study typeDiagnostic
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet.
Scientific titleAssessment of the predictive value of cardiac MRI in anthracycline-induced cardiomyopathy in sarcoma patients
Study acronymCARETOX-1
Study objectivesEarly changes in cardiac tissue morphology assessable by cardiac MRI can predict the development of subsequent cardiomyopathy in sarcoma patients treated with anthracyclines.
Ethics approval(s)Ethics board at Charité University Medicine Berlin, Campus Mitte, 23/09/2014, ref: EA1/262/14
Health condition(s) or problem(s) studiedAnthracycline-induced cardiomyopathy in patients with sarcoma
InterventionCardiac tissue morphology is assessed in sarcoma patients treated with anthracycline-based chemotherapy using cardiac MRI. Patients receive at least three cardiac MRI scans: before start of chemotherapy (baseline), 24-48 hours after the first treatment and 3-4 weeks after completion of chemotherapy (usually after 4-5 months).

Blood analysis is carried out at the time of each MRI scan: NTproBnP, high-sensitive Troponin T, hematocrit, glomerular filtration rate. ECG is also carried out at the time of each MRI scan.
Intervention typeProcedure/Surgery
Primary outcome measureMyocardial T1 and T2 times, measured using parametric mapping techniques before start of chemotherapy (baseline), 24-48 hours after the first treatment and 3-4 weeks after completion of chemotherapy (usually after 4-5 months).
Secondary outcome measuresMeasured before start of chemotherapy (baseline), 24-48 hours after the first treatment and 3-4 weeks after completion of chemotherapy (usually after 4-5 months):
1. Left and right atrial and ventricular size and function, measured in CINE sequences
2. Detection and size of myocardial fibrosis using late gadolinium enhancement techniques
3. Detection of arrhythmia using ECG
4. Laboratory blood analysis parameters (NTproBNP, hematocrit, high sensitive troponin T, glomerular filtration rate)
Overall study start date01/10/2014
Completion date31/12/2016

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants30 patients with first exposure to anthracyclines, 30 patients with re-exposure to anthracyclines
Key inclusion criteria1. Histologically confirmed sarcoma diagnosis
2. Planned chemotherapy with anthracyclines (cumulative dose >300 mg/m2 doxorubicin-equivalent)
3. Age at least 18 years (no upper limit)
Key exclusion criteria1. Any contraindication for contrast-based MRI
2. Chronic renal failure (glomerular filtration rate <30ml/min)
3. Previous participation in this study
Date of first enrolment01/10/2014
Date of final enrolment31/12/2019

Locations

Countries of recruitment

  • Germany

Study participating centre

HELIOS Clinic Berlin-Buch
Berlin
13125
Germany

Sponsor information

Charité University Medicine Berlin
University/education

Working Group Kardiale MRT
Lindenberger Weg 80
Berlin
13125
Germany

Website http://www.cmr-berlin.org
ROR logo "ROR" https://ror.org/001w7jn25

Funders

Funder type

University/education

Charité Universitätsmedizin Berlin
Private sector organisation / For-profit companies (industry)
Alternative name(s)
Medical School - Charité - University Medicine Berlin
Location
Germany
HELIOS Kliniken
Private sector organisation / For-profit companies (industry)
Alternative name(s)
HELIOS Kliniken GmbH
Location
Germany

Results and Publications

Intention to publish date28/02/2018
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planResults of this study shall be published in two high-ranking peer-reviewed journal publication. One publication for each study group (group 1: first exposure to anthracyclines, group 2: re-exposure to anthracyclines - for details see above).
IPD sharing planThe datasets generated during and/or analysed during the current study are not expected to be made available due to data protection laws in Germany. However, upon request methodology and dataset structure can be shared.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/08/2018 03/07/2019 Yes No
Results article results 21/02/2019 29/01/2020 Yes No

Editorial Notes

29/01/2020: Publication reference added.
03/07/2019: Publication reference added.