Early Detection of Imaging-derived Subclinical Cardiac Injuries (EMIRA)

• ClinicalTrials.gov Identifier: NCT03575650
• Recruitment Status: Recruiting
• First Posted: July 2, 2018
• Last Update Posted: February 28, 2024
• Sponsor: University Medical Center Groningen
• Collaborator: Utrecht University
• Information provided by (Responsible Party): University Medical Center Groningen

Tracking Information

• First Submitted Date: June 18, 2018
• First Posted Date: July 2, 2018
• Last Update Posted Date: February 28, 2024
• Actual Study Start Date: January 24, 2019
• Estimated Primary Completion Date: September 2, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 28, 2018)

Left Ventricle Global Longitudinal Strain (LV-GLS) assessed by echocardiography [ Time Frame: 6 and 24 months after radiotherapy with reference to baseline ]

Increasement in left ventricle Global Longitudinal Strain (GLS) of at least 5%

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 28, 2018)

• Changes in myocardial function assessed by echocardiography [ Time Frame: 6 and 24 after completion of radiotherapy with reference to baseline ]
  Increasement of segmental strain measurements (unit of measures:%)
• Anatomical changes in coronary arteries by cardiac CT [ Time Frame: 6 and 24 after completion of radiotherapy with reference to baseline ]
  Increase in the number of coronary segments containing any plaque/stenosis, or increase in calcium score
• Myocardial tissue abnormalities assessed by cardiac MRI [ Time Frame: 6 and 24 after completion of radiotherapy with reference to baseline ]
  Increase of the native mean myocardial T1 mapping value assessed by cardiac MRI

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Early Detection of Imaging-derived Subclinical Cardiac Injuries
• Official Title: Early Detection of Imaging-derived Subclinical Cardiac Injuries After Radiotherapy and Chemotherapy for Breast Cancer
• Brief Summary: Breast cancer (BC) radiotherapy leads to incidental cardiac irradiation, resulting in an increased risk of various major cardiac events (MCEs). In addition, recent studies indicate that for the treatment of BC, the addition of chemotherapy further enhances the risk of MCEs. Information regarding morphological and functional early subclinical cardiac injuries (ESCIs) induced by chemotherapy and radiotherapy that develop into MCEs is largely lacking in scientific literature. This information is essential towards the development of primary and secondary preventive strategies. The EMIRA prospective cohort has as main objective to identify morphological and functional ESCIs in BC patients treated with adjuvant radiotherapy and chemotherapy.

Detailed Description

EMIRA is a single centre prospective observational cohort study performed in the UMCG. The study includes breast cancer patients that underwent primary surgery, either by mastectomy or breast conserving surgery, who are treated with adjuvant radiotherapy and chemotherapy as part of routine clinical care. The patient follow up time continues for 2 years after radiotherapy to identify early subclinical cardiac injuries (ESCIs), using repeat echocardiography (cECHO), cardiac MRI (cMRI) scans and cardiac CT (cCT) scans. The images are acquired prior to chemotherapy and/or radiotherapy (depending on the sequence of adjuvant treatment), and at 6 and 24 months after radiotherapy The first primary aim of this project is to detect ESCIs that are considered risk factors for clinically apparent major cardiac events in breast cancer patients treated with radiotherapy and chemotherapy. The second is to use this information to develop prediction models describing the relationship between the radiation dose to cardiac substructures and ESCIs.

In detail, the investigators aim to:

1. identify longitudinal morphological and functional ESCIs using echocardiography, cardiac MRI and cardiac CT before and after BC treatment;
2. determine the relationship between 3D-dose distributions to cardiac substructures and ESCI;
3. establish the effect of chemotherapy on the dose-effect relationship between radiation dose and ESCI.

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Female patients with unilateral BC aged 40-75 years who underwent primary surgery, either by mastectomy or by breast conserving surgery, who are treated with adjuvant radiotherapy and chemotherapy as part of routine clinical care.
• Condition: Cardiovascular Diseases

Intervention

Other: Cardiac imaging modalities

Repeat cardiac echocardiographies, MRI-scans and CT-scans for early subclinical biomarker assessments in breast cancer patients treated with chemotherapy and radiotherapy

Study Groups/Cohorts

Cardiac imaging modalities

Repeat echocardiography (cECHO), cardiac MRI (cMRI) scans and cardiac CT (cCT) scans will be performed to evaluate myocardial dysfunction and deformation; myocardium inclusing tissue abnormalities, cardiac morphology and function and; coronary artery lesions and coronary artery calcium score.

Intervention: Other: Cardiac imaging modalities

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 28, 2018): 148
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2, 2024
• Estimated Primary Completion Date: September 2, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Female unilateral BC patients
2. Primary breast conserving surgery or mastectomy for stage I-III invasive adenocarcinoma of the breast or ductal carcinoma in situ (DCIS)
3. Age between 40-70 years at time of chemotherapy/radiotherapy
4. WHO performance status 0-1
5. Planned radiotherapy to the breast/chest wall with or without the lymph node areas
6. Radiotherapy based on planning CT-scan, using either 3D CRT, (partial) IMRT or (partial) VMAT/RapidArc with or without deep inspiration breath-hold
7. Adjuvant systemic chemotherapy (before or after radiotherapy)
8. Written informed consent

Exclusion Criteria:

1. Male BC patients
2. M1 disease (metastatic BC)
3. Previous thoracic or mediastinal radiation
4. Neo-adjuvant chemotherapy not allowed
5. Targeted HER2 therapy not allowed
6. Medical history of coronary artery disease and/or myocardial infarction and/or atrial fibrillation
7. Contraindications to injection of iodinated contrast such as allergy or renal failure
8. Pregnancy or lactation
9. Atrial fibrillation detected during electrocardiogram before chemotherapy/radiotherapy
10. Abnormal echocardiography before chemotherapy/radiotherapy defined as: LVEF <50%, longitudinal strain <-16%, longitudinal strain rate <-1%, and/or abnormal wall motion
11. Presence of myocardial infarction detected during cMRI before chemotherapy/radiotherapy
12. cMRI or cCT results before chemotherapy/radiotherapy requiring revascularisation

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 40 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Anne Crijns, MD, PhD; +31503616161; a.p.g.crijns@umcg.nl

• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03575650
• Other Study ID Numbers: 2018-06
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: University Medical Center Groningen
• Original Responsible Party: A.P.G. Crijns, University Medical Center Groningen, Radiation Oncologist
• Current Study Sponsor: University Medical Center Groningen
• Original Study Sponsor: Same as current
• Collaborators: Utrecht University

Investigators

• Study Chair: Hans Langendijk, Prof.Dr; UMCG

• PRS Account: University Medical Center Groningen
• Verification Date: February 2024