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

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

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases; Oncologic Disorders
• Intervention / Treatment: Other: Cardiac Rehabilitation Program; Other: Community exercise intervention

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Portugal
  • Porto
    • Vila Nova De Gaia, Porto, Portugal, 4434-502
      • Centro Hospitalar Vila Nova de Gaia Espinho, E.P.E.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cardiac Rehabilitation Program (CRP) Group; 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; 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
Active Comparator: Community Exercise Group; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Associacao de Investigacao de Cuidados de Suporte em Oncologia
• Collaborators: Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.; University Institute of Maia

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2021
• Primary Completion (Actual): June 23, 2022
• Study Completion (Actual): July 5, 2022

Study Registration Dates

• First Submitted: September 27, 2021
• First Submitted That Met QC Criteria: November 13, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2022
• Last Update Submitted That Met QC Criteria: October 1, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: exercise training; cardiovascular risk factors; cardiorespiratory fitness; cardiac rehabilitation; cardio-oncology rehabilitation
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: CORE Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No