Cancer Survivorship, Cancer Therapy-Related Cardiac Dysfunction, Cardio-oncology, Cardiovascular Risk, Heart Failure
Conditions
Keywords
Structured Cardio-Oncology Rehabilitation, Cardiac Rehabilitation, Cancer Survivors, Major Adverse Cardiovascular Events, Exercise Training, Cardiorespiratory Fitness, CTRCD
Brief summary
Cancer therapy-related cardiac dysfunction (CTRCD) has become a major cause of morbidity and mortality among cancer survivors. Although cardiac rehabilitation is recommended for cardiovascular disease prevention and management, high-quality randomized controlled evidence regarding its efficacy in cardio-oncology populations remains limited. This multicenter, prospective, parallel-group, superiority randomized controlled trial aims to evaluate whether a structured cardio-oncology rehabilitation (CORE) program combined with usual care can improve cardiovascular outcomes in patients with CTRCD or cancer survivors at high cardiovascular risk, compared with usual care alone. A total of 800 participants will be randomized in a 1:1 ratio to receive either structured cardio-oncology rehabilitation plus usual care or usual care alone. The intervention includes individualized exercise training, nutritional management, psychosocial support, cardiovascular risk-factor optimization, and patient education. Participants will be followed for 12 months. The primary endpoint is time to first major adverse cardiovascular event (MACE) within 12 months. Secondary endpoints include changes in cardiorespiratory fitness, cardiac function, biomarkers, quality of life, physical function, psychological status, safety outcomes, and health economic outcomes.
Detailed description
With advances in anti-cancer therapies, the number of cancer survivors has increased substantially worldwide. However, cancer therapy-related cardiac dysfunction (CTRCD) has emerged as a major long-term complication associated with increased cardiovascular morbidity, mortality, reduced quality of life, and impaired survival. Current management strategies primarily focus on pharmacologic prevention and treatment, while evidence-based non-pharmacologic interventions capable of improving hard cardiovascular outcomes remain insufficient. Cardiac rehabilitation is a Class I recommended intervention for patients with cardiovascular diseases and has demonstrated benefits in improving cardiorespiratory fitness, reducing cardiovascular events, and enhancing quality of life. Emerging studies suggest that cardio-oncology rehabilitation may improve exercise capacity and cardiac function in cancer survivors; however, most existing studies are limited by small sample size, single-center design, and lack of hard clinical endpoints. This study is a multicenter, prospective, parallel-group, superiority randomized controlled trial designed to evaluate the efficacy and safety of a structured cardio-oncology rehabilitation (CORE) program in patients with CTRCD or cancer survivors at high cardiovascular risk. A total of 800 participants will be enrolled and randomized in a 1:1 ratio to either: 1. Structured cardio-oncology rehabilitation plus usual care; or 2. Usual care alone. The intervention consists of a 12-week intensive rehabilitation phase followed by long-term maintenance guidance. Core components include: * Individualized aerobic and resistance exercise training; * Nutritional assessment and management; * Psychosocial and behavioral support; * Intensive cardiovascular risk-factor management; * Patient education and self-management support. The primary endpoint is time to first major adverse cardiovascular event (MACE) within 12 months, including cardiovascular death, myocardial infarction, ischemic stroke, hospitalization for worsening heart failure, or urgent ICD/CRT implantation due to malignant arrhythmia or heart failure. Secondary endpoints include: * Changes in peak oxygen uptake (VO2peak); * Changes in left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS); * Biomarkers including hs-cTnI and NT-proBNP; * Quality-of-life assessments; * Physical function measures; * Psychological outcomes; * Safety outcomes and health economic outcomes. Outcome assessment personnel, laboratory staff, endpoint adjudicators, and statisticians will remain blinded to treatment allocation. The study includes centralized imaging review, standardized intervention protocols, electronic data capture, and oversight by an independent Data and Safety Monitoring Board (DSMB). The findings of this trial are expected to provide high-quality evidence supporting the implementation of standardized cardio-oncology rehabilitation strategies in cancer survivors with cardiovascular toxicity or elevated cardiovascular risk.
Interventions
BEHAVIORALStructured Cardio-Oncology Rehabilitation
A structured cardio-oncology rehabilitation program including individualized aerobic and resistance exercise training, nutritional management, psychosocial support, cardiovascular risk-factor optimization, and patient education. The intervention consists of a 12-week intensive rehabilitation phase followed by maintenance rehabilitation guidance through 12 months.
BEHAVIORALUsual Care
Participants receive routine oncology and cardiovascular follow-up and general health advice without structured cardio-oncology rehabilitation or supervised exercise training.
Sponsors
Xinjiang Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Participants, care providers, and treating investigators cannot be masked because of the nature of the rehabilitation intervention. Outcome assessors, laboratory staff, endpoint adjudicators, and statisticians will remain blinded to treatment allocation.
Intervention model description
Participants will be randomized in a 1:1 ratio to receive either structured cardio-oncology rehabilitation plus usual care or usual care alone.
Eligibility
Sex/Gender
ALL
Age
18 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older, regardless of sex. * Histologically or cytologically confirmed solid tumor or hematologic malignancy. * Completed curative anti-cancer therapy, or receiving stable adjuvant, maintenance, or palliative anti-cancer therapy. * Meets at least one criterion for cancer therapy-related cardiac dysfunction (CTRCD) or high cardiovascular risk, including reduced LVEF after anti-cancer therapy, high-dose anthracycline exposure, chest radiotherapy with cardiovascular risk factors, heart failure after anti-cancer therapy, or elevated cardiac injury/heart failure biomarkers. * Estimated life expectancy of at least 24 months as assessed by the treating oncologist. * Able to complete baseline cardiopulmonary exercise testing and has no absolute contraindication to exercise training. * Able and willing to provide written informed consent and comply with study intervention and follow-up.
Exclusion criteria
* Active progressive malignancy requiring urgent anti-cancer therapy, or estimated life expectancy less than 24 months. * Severe structural heart disease, including severe valvular disease, congenital heart disease, end-stage heart failure, or waiting for heart transplantation or left ventricular assist device implantation. * Absolute contraindications to exercise training, including uncontrolled malignant arrhythmia, acute myocarditis or pericarditis, acute coronary syndrome within 2 weeks, severe anemia, severe thrombocytopenia or neutropenia, uncontrolled hypertension, active infection, or severe musculoskeletal disease preventing exercise training. * Participation in a structured cardiac rehabilitation program within the previous 12 months, or regular moderate-to-vigorous aerobic or resistance training for at least 3 months before enrollment. * Implanted ICD or CRT, except pacemakers with exercise mode. * Severe psychiatric disease or cognitive impairment preventing participation. * Concurrent participation in another interventional clinical trial, or planned participation in another interventional clinical trial during the study period. * Any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Major Adverse Cardiovascular Event (MACE) | From randomization to 12 months | Time from randomization to the first occurrence of a major adverse cardiovascular event (MACE), including cardiovascular death, myocardial infarction, ischemic stroke, hospitalization for worsening heart failure, or urgent ICD/CRT implantation due to malignant arrhythmia or heart failure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peak Oxygen Uptake | From baseline to 12 months | Change in peak oxygen uptake (VO2peak) measured by cardiopulmonary exercise testing. |
| Change in HADS Depression Score | From baseline to 12 months | The Hospital Anxiety and Depression Scale (HADS) Depression subscale ranges from 0 to 21, with higher scores indicating greater depressive symptoms. |
| Change in Left Ventricular Ejection Fraction | From baseline to 12 months | Change in left ventricular ejection fraction (LVEF) measured by three-dimensional echocardiography. |
| Change in Global Longitudinal Strain | From baseline to 12 months | Change in global longitudinal strain (GLS) measured by echocardiography. |
| Change in NT-proBNP | From baseline to 12 months | Change in N-terminal pro-B-type natriuretic peptide level. |
| Exercise-Related Adverse Events | From randomization to 12 months | Incidence of adverse events related to the rehabilitation intervention or exercise training. |
| Change in High-Sensitivity Cardiac Troponin I | From baseline to 12 months | Change in high-sensitivity cardiac troponin I level. |
| Change in 6-Minute Walk Distance | From baseline to 12 months | Change in 6-minute walk distance measured by the 6-minute walk test. |
| Change in SF-36 Score | From baseline to 12 months | Change in the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) score. Scores range from 0 to 100, with higher scores indicating better health-related quality of life. |
| Change in EORTC QLQ-C30 Global Health Status Score | From baseline to 12 months | Change in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status score. Scores range from 0 to 100, with higher scores indicating better quality of life. |
| Change in Hospital Anxiety and Depression Scale (HADS) Anxiety subscale score. | From baseline to 12 months | The Hospital Anxiety and Depression Scale (HADS) Anxiety subscale ranges from 0 to 21, with higher scores indicating greater anxiety symptoms. |
| Anti-Cancer Treatment Interruption | From randomization to 12 months | Incidence of interruption of anti-cancer treatment during the study period. |
Countries
China
Contacts
CONTACTXiang Xie, PhD
Outcome results
None listed