Impact of a Comprehensive Cardiac Rehabilitation Program Framework Among High Cardiovascular Risk Cancer Survivors

Study Overview
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Brief Summary
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Many cancer survivors are at risk for cardiovascular disease (CVD); it is therefore important to identify patients at increased risk for cardiotoxicity, especially in the setting of CVRF or pre-existing CVD, and to design personalized interventions to prevent cardiovascular morbidity. In this background, cardio-oncology rehabilitation frameworks for specific cancer patients have been proposed. Given potential beneficial effects of exercise among cancer patients (including those at higher risk of CVD), data pertaining to optimal program designs are of paramount contemporary importance. Thus, the aim of this study is to compare the impact of a Cardiac Rehabilitation Program (CRP) model versus a community-based exercise intervention plus usual care on cardiorespiratory fitness (CRF), physical function domains and CVRF control in adult cancer survivors who have been exposed to cardiotoxic cancer treatment and/or with cardiovascular medical background. Study outcomes will be assessed at baseline (M0) and after an 8 weeks-intervention (M1), comprising maximal aerobic capacity (peak oxygen uptake), muscular strength, neuromuscular function, single CVRF control including physical activity measurements and psychosocial parameters, health-related quality of life, fatigue, health literacy, inflammatory response and feasibility metrics; an economic evaluation will provide quantitative comparison, for a cost-effectiveness analysis

Official Title
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Impact of a Comprehensive Cardiac Rehabilitation Program Framework Among High Cardiovascular Risk Cancer Survivors

Conditions
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Oncologic Disorders, Cardiovascular Diseases

Intervention / Treatment
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* Other: Cardiac Rehabilitation Program
* Other: Community exercise intervention


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age >18 years Cancer survivors exposed to the following therapies: high-dose anthracycline or high dose radiotherapy in thoracic wall low-dose anthracycline or anti-human Epidermal growth factor Receptor-type 2 drugs (anti-HER2) alone plus ≥ 2 CVRF and / or age ≥ 60 years at cancer treatment low-dose anthracycline followed by anti-HER2; Cancer survivors with medical background of coronary artery disease moderate valvular disease LVEF <50% Follow up after primary treatment with curative intent Conclusion of primary treatment at least 2 months before the inclusion Exclusion criteria: Previous participation in a CRP Contraindications to exercise training: musculoskeletal or neurologic disorders, cognitive impairment unstable angor pectoris, decompensated HF, active myocarditis, acute endocarditis, acute pulmonary thromboembolism, complex ventricular arrhythmias Active cancer Considered unsuitable as per principal investigator judgment (namely due to expected inability to fulfill proposed schedule)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cardiac Rehabilitation Program (CRP) Group<br>Baseline consultation with physiatrist specialized in CRP - addressing CVRF control, comorbidities and disabilities; case-by-case discussion with a cardiologist specialized in CR will be undertaken, for tailoring exercise prescription. Nutritional individualized plan addressing dietary goals. Psychological management addressing psychosocial outcomes and motivation for healthy lifestyle habits Multidisciplinary team educational meeting: periodic group sessions with health education purposes Exercise intervention - 2 times/week sessions at CR facilities, supervised by a physiatrist, conducted by physiotherapist. Heart rate (HR) continuously monitored during each session by remote electrocardiographic monitoring or HR monitor. Exercise intensity estimated according to CR guidelines, determined after CV risk stratification, using CPET results. | Other: Cardiac Rehabilitation Program<br>* In addition to standard medical care, for an 8-week period, patients will have access to the core components of a CRP, delivered by a multidisciplinary rehabilitation team<br>|
| Active Comparator: Community Exercise Group<br>a) Besides standard medical and supportive care, psychological and nutritional individual support will be offered on demand, in hospital setting, according to the attending physician standard clinical assessment and usual care. Exercise intervention - Performed at a community-based facility, comprising 2 sessions/week, prescribed according to current physical activity guidelines for cancer survivors. Exercise intervention will be conducted by an exercise physiologist, internationally certified in exercise for cancer patients | Other: Community exercise intervention<br>* In addition to standard medical care, for an 8-week period, patients will have access to a community exercise intervention oriented by a sports professional<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiorespiratory fitness | VO2peak measured by CPET | Change from baseline to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilatory efficiency | minute ventilation to carbon dioxide production slope (VE/VCO2 slope) assessed by CPET | Change from baseline to 2 months | 
| Sit-to-stand test | Sit-to-stand test during 60 seconds | Change from baseline to 2 months | 
| Handgrip maximal isometric muscle strength | muscle strength measured with manual dynamometers (Kgf) | Change from baseline to 2 months | 
| Body composition | Changes in body composition assessed by bioelectrical impedance analysis | Change from baseline to 2 months | 
| Resting diastolic blood pressure | Measured with an average of 3 readings by an automated measurement device as per the ESC guidelines (mmHg) | Change from baseline to 2 months | 
| Resting systolic blood pressure | Measured with an average of 3 readings by an automated measurement device as per the ESC guidelines (mmHg) | Change from baseline to 2 months | 
| Resting heart rate | Measured with an average of 3 readings by an automated measurement device (bpm) | Change from baseline to 2 months | 
| Hyperlipidemia | Measured through fasting Blood biochemistry including total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), triglycerides (TG) | Change from baseline to 2 months | 
| Diabetes control | Measured through glycated haemoglobin (%) in fasting state | Change from baseline to 2 months | 
| Physical Activity | Self-reported through the International Physical Activity Questionnaire, classifying the activity in three categories (low activity levels, moderate activity levels or high activity levels) | Change from baseline to 2 months | 
| Physical Activity | objectively assessed by accelerometer, to wear for seven consecutive days | Change from baseline to 2 months | 
| Smoking Cessation | Cigarette smoking habits quantified in pack-year and cigarettes per day, to measure exposure to tobacco | Change from baseline to 2 months | 
| Depression and anxiety | Psychosocial parameters assessed through the Hospital Anxiety and Depression Score questionnaire. Scores 0-14. A sub-scale score > 8 denotes anxiety or depression symptoms | Change from baseline to 2 months | 
| Health Related Quality of Life | Evaluated using the EuroQuol Five- Dimensional questionnaire ( EQ-5D-5L). It consists in five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ - Visual Analog Scale records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. | Change from baseline to 2 months | 
| Fatigue | Fatigue score evaluated by the specific item on the EORTC QLQ-C30 questionnaire (high score representing high level of symptomatology) | Change from baseline to 2 months | 
| Health Literacy | Assessed by the Newest Vital Sign questionnaire; range score 0-6 (high score corresponding to high health literacy) | Change from baseline to 2 months | 
| Inflammatory markers- Interleukin-6 (IL-6) | Blood samples collected to access plasma levels of IL-6 | Change from baseline to 2 months | 
| Inflammatory markers - High-sensitivity C-reactive protein | Blood samples collected to access plasma levels of high-sensitivity C-reactive protein | Change from baseline to 2 months | 
| Feasibility - Consent rate | number of patients who met inclusion criteria divided by the number who consented in writing to participate. Reasons for not participating in the study will be registered. | Through study recruitment, up to 2 years | 
| Testing and Intervention Adverse events | all the events will be recorded and registered as related or unrelated to the intervention itself, as well as the impact for exercise concerns or other health intervention required | Change from baseline to 2 months | 
| Feasibility - Retention rate | number of participants who remained in the study (without formally drop out during intervention). | Change from baseline to 2 months | 
| Feasibility - Intervention adherence | total number of exercise sessions attended by participants allocated to this intervention group. Reasons for dropping out will be registered. | Change from baseline to 2 months | 
| Feasibility - Completion rate | number of patients that completed all the evaluations during the defined timeline. | Change from baseline to 2 months | 
| Cost-effectiveness analysis | Incremental cost per quality-adjusted life. Costs will be calculated from the provider perspective, which includes the costs incurred by the health institution providing health services; and from the societal perspective | From baseline assessment up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac rehabilitation, cardio-oncology rehabilitation, exercise training, cardiorespiratory fitness, cardiovascular risk factors