Heart and Blood Diseases

All Conditions

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Heart Failure

Cardiotoxicity

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

All Drugs and Chemicals

Tin Fluorides

Angiotensin Receptor Antagonists

Adrenergic beta-Antagonists

Enzyme Inhibitors

Angiotensin-Converting Enzyme Inhibitors

Fluorides

Protective Agents

This group will stop their heart failure medication(s) under the supervision of the study team. The investigators expect most participants in the STOP group to only be on beta-blockers and/or angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). The ACEi or ARB will be stopped first. The ACEi or ARB will be reduced by 50% every 7 days and stopped 7 days after 25% of maximal recommended dose for HF is reached. At this point (or at baseline if only on BB), the BB dose will be reduced by 50% every 7 days then stopped once 25% of the maximal dose is reached.

This group with continue with their heart failure medication(s) for at least 1 year.

This group will stop their heart failure medication(s) under the supervision of the study team.

Stopping Heart Failure Medication(s)

Paaladinesh Thavendiranathan, MD

Anju Nohria, MD

Tom Marwick, MD

James White, MD

Edith Pituskin, PhD

Davinder Jassal, MD

Darryl Leong, MD

Ian Paterson, MD

Kim Connelly, MD

Charlotte Manisty, MD

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 and 9 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.

The STOP-MED CTRCD Trial

A Multi-Centre Non-Inferiority Randomized Controlled Trial of STOPping Cardiac MEDications in Patients With Normalized Cancer Therapy Related Cardiac Dysfunction: The STOP-MED CTRCD Trial

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%.

Proportion of participants with new diastolic dysfunction or worsening diastolic function ≥1 grade by echocardiography between the two study groups.

Difference in proportion of participants with clinical HF between the two groups.

Difference in patient questionnaires scores between the two groups using the following patient questionnaires:

1. Kansas City Cardiomyopathy Questionnaire
2. SF-36
3. EQ-5D-5L

Differences in the GENESIS-PRAXY score between groups

Incidence of novel biomarkers and genomic factors that may determine the risk of developing the primary endpoint between the two groups.

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% 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.

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.

Doubling of NT-pro BNP compared to pre-HF therapy cessation between the two study groups.

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

We will compare the cost per quality adjusted life years between the two study groups.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
The STOP-MED CTRCD Trial	NCT06183437	Heart Failure Cardiotoxicity Cardiac Toxicit... Antineoplastics... Cancer	Stopping Heart ...	18 Years -	University Health Network, Toronto
The STOP-MED CTRCD Trial	NCT06183437	Heart Failure Cardiotoxicity Cardiac Toxicit... Antineoplastics... Cancer	Stopping Heart ...	18 Years -	University Health Network, Toronto

Spots Global Cancer Trial Database for cancer therapy related cardiac dysfunction