Risk-guided Disease Management Plan to Prevent Heart Failure in Patients Treated With Previous Chemotherapy (REDEEM)

Study Overview
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Brief Summary
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This is a prospective study in which a process of identifying and reducing heart failure (HF) risk will be applied to cancer survivors >65 years old with chemotherapy >10 years ago. The overall goal of this study to identify the feasibility and value of risk-guided cardiac rehabilitation (exercise, risk factor modification, and behavioural support) as a component of survivorship care.

Detailed Description
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Participants enrolled in this study will be randomized to cardio-oncology disease management plan ( CO-DMP) that involves the use of surveillance imaging to detect subclinical left ventricular dysfunction (LVD), clinical review to ensure optimal risk factor control and cardio-protection and exercise/sedentariness intervention. The intervention will be delivered over a period of 12 months. The outcome from this study will show that subclinical LVD is more common among long term cancer survivors, and a CO-DMP is feasible in reducing HF risk factors in this sub group of survivors.

Official Title
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Risk-guided Disease Management Plan to Prevent Heart Failure in Patients Treated With Previous Chemotherapy (REDEEM)

Conditions
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Heart Failure

Intervention / Treatment
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* Other: Heart Failure intervention (Cardio-Oncology Disease Management Plan (CO-DMP)
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of cancer > 10 years ago Have received potentially toxic chemotherapy Anthracycline (any dose) Trastuzumab (Herceptin) in breast-cancer with the HER2 mutation OR Tyrosine kinase inhibitors (e.g. sunitinib) OR Left chest radiotherapy Exclusion Criteria: Ejection fraction at baseline echo <50% Valvular stenosis or regurgitation of >moderate severity History of previous heart failure (baseline New York Heart Association (NYHA) classification >2) Systolic BP <110 mmHg Pulse <60/minute if not on beta blocker Inability to acquire interpretable images (identified from baseline echo) Contraindications to beta blockers or angiotensin-converting enzyme inhibitors Oncologic (or other) life expectancy <12 months or any other medical condition (including pregnancy) that results in the belief (deemed by the Chief Investigators) that it is not appropriate for the patient to participate in this trial Already taking both angiotensin converting enzyme inhibitors/angiotensin receptor blockers and beta blockers, or intolerance (or allergy) to both. Unable to provide written informed consent to participate in this study

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization to CO-DMP or usual care
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Heart failure intervention ( Cardio-Oncology Disease Management Plan (CO-DMP)<br>Optimization of pharmacotherapy: Cardioprotection with angiotensin-converting enzyme inhibitor (ACEi, Ramipril) and beta blocker (Metoprolol).Participants will be initially treated with ramipril at a dose of 1.25 or 2.5mg (according to baseline systemic arterial pressure), once or twice a day, and gradually up-titrated to 10mg/day, or to the maximal-tolerated dose. In patients receiving at least 2.5mg/day of ramipril, metoprolol will be started at an initial dose of 50 (25mg twice a day) and progressively up-titrated to the maximal dose of 100mg/day. Patients will be reviewed every 2 weeks during the up titration phase. Exercise intervention: Individualized training program provided by an exercise physiologist. | Other: Heart Failure intervention (Cardio-Oncology Disease Management Plan (CO-DMP)<br>* A clinical review to ensure optimal risk factor control and cardioprotection along with exercise intervention.<br>|
| Active Comparator: Usual care<br>Provided by participants' usual healthcare professional(s), guided by a brochure regarding optimal risk factor management addressing hypertension, lipids, alcohol intake and tobacco use. | Other: Usual care<br>* provided by participants' usual healthcare professional(s)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in exercise capacity | Cardio pulmonary fitness (peak oxygen uptake (VO2 peak)) from baseline to follow up. | Over a period of 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication adherence | proportion of ACEi and beta blocker tablets taken | Over a period of 12 months | 
| Neuromuscular strength | Maximal isometric grip strength (kg) assessed using a digital grip strength dynamometer | Over a period of 12 months | 
| Endurance | Increase in total exercise duration. | Over a period of 12 months |