Exercise-based Cardiac Rehabilitation for the Prevention of Breast Cancer Chemotherapy-induced Cardiotoxicity

Cardiotoxicity Clinical Trial

— ONCORE  

Official title:

Randomized Controlled Trial on Comprehensive Exercise-based Cardiac Rehabilitation Programs for the Prevention of Anthracyclines and/or Anti-HER2 Antibodies-induced Cardiotoxicity in Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03964142
• Other study ID #: PI17/01687
• Status: Completed
• Phase: N/A
• Start date: August 1, 2018
• Est. completion date: January 1, 2023

Study information

• Verified date: May 2023
• Source: Hospital Clinico Universitario de Santiago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This project aims to determine whether a comprehensive cardiac rehabilitation program including supervised exercise training is able to prevent cardiotoxicity during treatment with anthracyclines and / or anti-HER-2 antibodies in women with breast cancer. Participants will be randomly allocated to cardiac rehabilitation (intervention group) or conventional management with physical exercise recommendation (control group).

Description:

Cardiovascular toxicity caused by chemotherapy is the leading cause of death in patients who survive cancer. Physical exercise during chemotherapy has shown to improve quality of life and decrease the risk of death. The objective of this project is to determine whether an intervention through a comprehensive cardiac rehabilitation program including supervised physical exercise is able to prevent anthracyclines and / or anti-HER-2 antibodies-induced cardiotoxicity in women with breast cancer.

For this purpose, the investigators intend to conduct a randomized controlled study including female patients managed under the same cardiotoxicity prevention protocol (clinical, laboratory and echocardiographic follow-up assessment). Patients will be randomized to a non-pharmacological intervention (participation in a multidisciplinary cardiac rehabilitation program with supervised exercise training) or control (conventional management and physical activity recommendation)*.

The investigators hypothesize that a cardiac rehabilitation program may limit chemotherapy-induced cardiotoxicity in women with breast cancer, improve cardiac remodeling assessed by echocardiography and enhance their global cardiovascular risk profile to a greater extent, compared to control group.

• OF NOTE: Due to the COVID-19 pandemics, several modifications to the original protocol were introduced for safety reasons or motivated by the health situation, namely:

1. Intervention: Change from centre-based to telematic supervised exercise training sessions provided within the cardiac rehabilitation program (intervention group)

2. Secondary outcome 4: Change in functional capacity assessed by conventional ergometry or cardiopulmonary exercise test OR the 6-minute walking test (metabolic equivalents: METs or peak oxygen consumption: VO2)

3. Recruiting centres: One centre (Hospital Universitari Vall d'Hebron) withdrew from the study due to the impossibility of assuming its execution.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: January 1, 2023
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 69 Years

Eligibility

Inclusion Criteria:

• First diagnosis of breast cancer at early stages (I, II, III)

• Treatment with anthracyclines and / or anti-HER-2 antibodies (trastuzumab and / or pertuzumab)

• Possibility of completing a cardiac rehabilitation program (centre-based or telematic) and programmed visits.

• Providing written informed consent.

Exclusion Criteria:

• Patients with previous history of heart disease or heart failure.

• Left ventricular dysfunction (left ventricular ejection fraction <53%) at baseline.

• Metastatic disease.

• Patients carrying an implantable cardioverter defibrillator.

• Patients with physical or mental limitation to carry out an exercise program.

Related Conditions & MeSH terms

• Cardiac Rehabilitation
• Cardiotoxicity

Intervention

Other:
• Cardiac rehabilitation
Integrated cardiac rehabilitation program that includes supervised exercise training*. * Due to the COVID-19 pandemic, supervised physical exercise training had to be conducted telematically (through live guided training sessions conducted online, with the same design, frequency, and dosage of exercise).

Locations

Country	Name	City	State
Spain	Hospital Clínico Universitario de Santiago	Santiago de Compostela	A Coruña

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Clinico Universitario de Santiago	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adherence and compliance to cardiac rehabilitation program (intervention group) assessed by number of training sessions attended/ number of sessions planned	Number of training sessions attended / number of sessions planned	At the end of the cardiac rehabilitation program at an average of 12 to 15 months
Other	Security of the cardiac rehabilitation program assessed by number of adverse events during training (intervention group)	Adverse events during training	At the end of the cardiac rehabilitation program at an average of 12 to 15 months
Other	Changes in expectations regarding the cardiac rehabilitation program assessed by a questionnaire (intervention group)	Program-related expectations at baseline and at the end of the program' are collected through an open question "What do you expect to achieve by participating in the program?" Responses regarding expectations will be categorized by the evaluator within the following areas: psychological sphere and/or social sphere and/or physical sphere. Global expectations of benefit are scored from 0 (no benefit) to 10 (highest benefit).	Baseline and at the end of the cardiac rehabilitation program at an average of 12 to 15 months
Other	Satisfaction with the cardiac rehabilitation program assessed by a questionnaire (intervention group)	Satisfaction at the end of the program is assessed by a questionnaire including 9 questions concerning comfort with training sessions, training spaces and development of the program, which are scored from 0 (worse posible result) to 10 (best posible result). Total score is calculated by adding for each question, and ranges from 0 to 90.; * Due to the introduction of telematic exercise training during COVID-19 pandemic, questions were slightly modified to include assessment of satisfaction with this training modality.	At the end of the cardiac rehabilitation program at an average of 12 to 15 months
Primary	Change in left ventricular systolic function quantified by left ventricular ejection fraction and global longitudinal strain by transthoracic echocardiography	Fall of 10 absolute percentage points of left ventricular ejection fraction with final value below 53% or global longitudinal strain fall >15% with respect to baseline	Baseline to every 3 months through study completion, at the end of the study at an average of 18 months, and every year after study completion up to a maximum of 5 years
Secondary	Change in health-related quality of life assessed by the Functional Assessment of Cancer Therapy - Breast plus Arm Morbidity (FACT-B+4) questionnaire	Score achieved in the Functional Assessment of Cancer Therapy - Breast plus Arm Morbidity (FACT-B+4) questionnaire, a specific validated scale to assess quality of life of women with breast cancer. It comprises 27 items within 5 areas of assessment: physical well-being (7 items), social and family environment (7 items), emotional well-being (7 items), functional well-being (6 items) and worries related to the diagnosis and treatment of the disease (9 items). Each item is scored by means of a Likert scale from 0 to 5, with higher scores representing better results. The total score is obtained by adding the scores for each item, and ranges from a minimum of 0 (worst posible result) to a maximum of 146 (best possible result).	Baseline and at the end of the study at an average of 18 months
Secondary	Change in tolerance to chemotherapy: number of participants with significant cardiovascular and non-cardiovascular adverse effects throughout the study	Significant cardiovascular and non-cardiovascular adverse effects during treatment, threatening life, requiring admission, prolonging hospitalization, being clinically relevant or causing chemotherapy interruptions	Every 3 months during study completion and at the end of the study at an average of 18 months
Secondary	Change in global functional capacity assessed by conventional ergometry, cardiopulmonary exercise testing (CPET) or the 6-minute walking test (6MWT).	Change in functional capacity assessed by conventional ergometry, cardiopulmonary exercise test or the 6-minute walking test (6MWT) (metabolic equivalents: METs or peak oxygen consumption: VO2) * .; *Due to COVID-19 pandemic, participants' assessment with CPET had to be stopped for safety concerns. In such cases, functional capacity was estimated from the maximum work rate in the 6-minute walking test (6MWT). This test measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes, which is well correlated with VO2. The 6MWT has been proved to be valid and reliable for functional capacity assessment in the study population.	Baseline and at the end of the study at an average of 18 months
Secondary	Change in localized lower limb functional capacity assessed by number of repetitions performed within 30 seconds in the sit-to-stand test	Number of repetitions in the sit-to-stand test within 30 seconds	Baseline and at the end of the study at an average of 18 months
Secondary	Change in shoulder functional capacity assessed by range of degrees in shoulder movement by goniometry	Range of degrees in shoulder movement measured by goniometry	Baseline and at the end of the study at an average of 18 months
Secondary	Change in upper limb strength measured by dynamometry (kg)	Kilograms by dynamometry of right and left upper limbs	Baseline and at the end of the study at an average of 18 months
Secondary	Change in shoulder pain and disability assessed by the SPADI (shoulder pain and disability index (SPADI) questionnaire	Score achieved in the SPADI (shoulder pain and disability index) questionnaire. The pain dimension consists of five questions regarding the severity of an individual's pain, functional activities are assessed with eight questions. Each question may be scored from 0 to 10. Verbal anchors for the pain dimension are 'no pain at all' (0) and 'worst pain imaginable' (10) ,and those for the functional activities are 'no difficulty' (0) and 'so difficult it required help' (10). The scores from both dimensions are averaged to produce a total score ranging from 0 (best) to 100 (worst).	Baseline and at the end of the study at an average of 18 months
Secondary	Change in cardiovascular risk profile as assessed by the presence or absence of classic cardiovascular risk factors	Dyslipidemia, Diabetes mellitus, Arterial Hypertension, Smoking status	Baseline and at the end of the study at an average of 18 months
Secondary	Change in anthropometric parameters: height in cm	Height measured in cm	Baseline and at the end of the study at an average of 18 months
Secondary	Change in anthropometric parameters: weight in kg	Weight measured in kg	Baseline and at the end of the study at an average of 18 months
Secondary	Change in anthropometric parameters: body mass index (BMI) in kg/m^2	Weight and height will be combined to report BMI in kg/m^2	Baseline and at the end of the study at an average of 18 months
Secondary	Change in anthropometric parameters: abdominal circumference in cm	Abdominal perimeter measured with a tape measure in cm	Baseline and at the end of the study at an average of 18 months
Secondary	Change in resting heart rate measured by pulse oximetry (beats per min)	Resting heart rate by pulse oximetry (beats per min)	Baseline and at the end of the study at an average of 18 months
Secondary	Change in resting blood pressure (mmHg) measured by sphygmomanometer	Resting blood pressure by sphyngomanometer in mmHg	Baseline and at the end of the study at an average of 18 months
Secondary	Change in biomarkers NT-ProBNP	Value of NT-ProBNP(pg/mL) in blood tests	Baseline and at the end of the study at an average of 18 months
Secondary	Change in biomarkers: troponin	Value of troponin I (ng/mL) in blood tests	Baseline and at the end of the study at an average of 18 months
Secondary	Change in biomarkers: haemoglobin	Value of haemoglobin (g/dL) in blood tests	Baseline and at the end of the study at an average of 18 months
Secondary	Change in dietary pattern as assessed by the PREDIMED (PREvención con DIeta MEDiterránea) questionnaire	Validated questionnaire to assess adherence to Mediterranean diet, including 14 questions regarding dietary habits, rated with 0 or +1 points. Global score is calculated by summing points and ranges from 0 to 14, with higher score representing higher adherence.	Baseline and at the end of the study at an average of 18 months
Secondary	Change in the score for depression assessed by Zigmond and Snaith questionnaire to rate anxiety and depression	Score achieved in the depression subscale of the Zigmond and Snaith test for anxiety or depression, a self-applied questionnaire. Depression scale includes 7 items each, scored on Likert scale from 0 to 3. Global score ranges from 0 to 21, with higher scores representing greater depression. The authors suggest that scores higher than eleven would indicate "case" and more than eight would be considered "probable case" (Zigmond and Snaith, 1983).	Baseline and at study completion at an average of 18 months, plus at the end of training (at an average of 12 to 15 months) in the intervention group
Secondary	Change in the score for anxiety assessed by the Zigmond and Snaith questionnaire to rate depression and anxiety	Score achieved in the anxiety subscale of the Zigmond and Snaith test for anxiety or depression, a self-applied questionnaire. Anxiety scale includes 7 items each, scored on Likert scale from 0 to 3. Global score ranges from 0 to 21, with higher scores representing greater anxiety. The authors suggest that scores higher than eleven would indicate "case" and more than eight would be considered "probable case" (Zigmond and Snaith, 1983).	Baseline and at study completion, plus at the end of training (at an average of 12 to 15 months) in the intervention group
Secondary	Change in physical activity (minutes of dedicated physical activity)	Minutes of In- and out-of-hospital dedicated physical activity	Baseline and at study completion at an average of 18 months
Secondary	Change in physical activity assessed by the score in the Godin Leisure Test Exercise Questionnaire (GLTEQ)	Score achieved in the Godin Leisure Test Exercise Questionnaire (GLTEQ) for quantification of physical activity. Activities are classified into three subgroups: "strenuous," "moderate," and "light." The scores corresponding to the energy expenditure (metabolic equivalent (MET)) are obtained by multiplying activities performed for more than 15 min in a week with their coefficients. The numbers represent the MET intensity values (strenuous/ exhausting exercises: 9 METs, moderate exercises: 5 METs, and light exercises: 3 METs).The increasing scores are associated with the increasing number of exercise behaviors, providing references about the contribution of physical activity to health: the activity score of 24 units and more as active (substantial benefits); the activity score of 14-23 units as moderately active (some benefits); and the activity score of 13 units and less as inactive (less substantial or low benefits).	Baseline and at study completion at an average of 18 months
Secondary	Change in lymphedema assessed by perimeter of the upper limb by cirtometry (cm), stage and grade	Perimeter of the upper limb by cirtometry (cm), stage and grade as defined by the Spanish Society of Rehabilitation and Physical Medicine	Baseline after surgery and 2-4 weeks after the end of chemotherapy (at an average of 12 to 15 months)