Cancer therapy-related cardiac dysfunction (CTRCD) is when the heart's ability to pump oxygenated blood to the body is compromised. It is a side effect of cancer therapy which can occur as commonly as in 1 in 5 patients. When this occurs, heart failure medications are started to protect the heart from progressing to heart failure. With early detection and treatment, heart function recovers to normal in \>80% of patients. Unfortunately, heart failure medications are associated with an undesirable long-term pill burden, financial costs, and side-effects (e.g., dizziness and fatigue). As a result, cancer survivors frequently ask if they can safely stop their heart failure medications once their heart function has returned to normal. Currently there is no scientific evidence in this area of Cardio-Oncology. To address this knowledge gap, the investigators have designed a randomized control trial to assess the safety of stopping heart failure medication in patients with CTRCD and recovered heart function. The investigators will enrol patients who have completed their cancer therapy and are on heart medications for their CTRCD, which has now normalized. The investigators will randomize patients with no other reasons to continue heart failure medications (e.g., kidney disease) to continuing or stopping their heart medications safely. All patients will undergo a cardiac MRI at baseline, 1 and 5 years with safety assessments at 6-8 weeks, 6 months and 3 and 5 years. The investigators will determine if stopping medications is non-inferior to continuing medications by counting the numbers of patients who develop heart dysfunction by 1 year in each group.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
335
This group will stop their heart failure medication(s) under the supervision of the study team.
Brigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGBaker Heart and Diabetes Institute
Melbourne, Victoria, Australia
RECRUITINGFoothills Medical Centre
Calgary, Alberta, Canada
NOT_YET_RECRUITINGEdmonton Clinic Health Academy
Edmonton, Alberta, Canada
NOT_YET_RECRUITINGSt. Boniface Hospital
Winnipeg, Manitoba, Canada
NOT_YET_RECRUITINGHamilton General Hospital
Hamilton, Ontario, Canada
NOT_YET_RECRUITINGUniversity of Ottawa Heart Institute
Ottawa, Ontario, Canada
NOT_YET_RECRUITINGSt Michael's Hospital
Toronto, Ontario, Canada
NOT_YET_RECRUITINGUniversity Health Network
Toronto, Ontario, Canada
RECRUITINGBarts Health NHS Trust, University College London
London, United Kingdom
NOT_YET_RECRUITINGCancer Therapy Related Cardiac Dysfunction Relapse
To compare the proportion of those that develop by 1 year of follow-up one or both of the following (i) left ventricular ejection fraction \<50% and an absolute decline of \>5% from baseline by cardiac magnetic resonance (CMR) (ii) new heart failure signs (at least two physical findings or one physical finding and one laboratory finding) AND symptoms (at least one) with the initiation of qualifying heart failure therapy.
Time frame: 1 year
Changes in cardiac magnetic resonance parameters
Differences between the two groups in the following measures. 1. Changes in CMR LVEF as a continuous parameter. 2. Proportion of participants with increased CMR indexed LV volumes by ≥10% to higher-than-normal limits. 3. Proportion of participants with decline in CMR LVEF to \<50% with a \>10% absolute fall compared to pre-HF medication withdrawal. 4. CMR peak systolic global longitudinal strain (GLS) worsening by \>15%.
Time frame: 1 year
Left ventricular diastolic function
Proportion of participants with new diastolic dysfunction or worsening diastolic function ≥1 grade by echocardiography between the two study groups.
Time frame: 1 year
Non-adherence of heart failure medication(s)
Proportion of participants with non-adherence of heart failure medication(s) by 1 year between the two study groups. Non-adherence is defined in the STOP group as the proportion of participants in whom successful cessation of all medications used to treat CTRCD was not possible or re-addition of the same medications used in that participant for HF was necessary for non-HF indications (e.g., palpitations). In the standard of care (SOC) group non-adherence is defined as the proportion of participants who stopped all HF medications used to treat CTRCD.
Time frame: 1 year
N-terminal pro B-type Natriuretic Peptide (NT-pro BNP)
Doubling of NT-pro BNP compared to pre-HF therapy cessation between the two study groups.
Time frame: 1 year
Changes in quality of life score
Difference in patient questionnaires scores between the two groups using the following patient questionnaires: 1. Kansas City Cardiomyopathy Questionnaire 2. Short Form (SF) Survey -36 3. EQ-5D-5L
Time frame: 1 year
Cost effectiveness analysis
We will compare the cost per quality adjusted life years between the two study groups.
Time frame: 1 year
Proportion of participants developing the primary outcome by whether they developed moderate versus severe CTRCD at original diagnosis
The proportion of those that develop the primary outcome stratified by CTRCD LVEF \<40% or ≥40%
Time frame: 1 year
Incidence of novel biomarkers and genomic factors that may determine the risk of developing the primary endpoint
Incidence of cardiac, inflammatory, endothelial and other novel biomarkers and genomic factors that may determine the risk of developing the primary endpoint.
Time frame: 1 year
Proportion of participants developing the primary outcome stratified by natriuretic peptides thresholds.
Proportion of participants developing the primary outcome stratified by natriuretic peptides thresholds.
Time frame: 1 year
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