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The STOP-MED CTRCD Trial

Recruiting
18 years of age
Both
Phase 4

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Overview

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.

Eligibility

Inclusion Criteria:

  • Adult patients (age ≥18 years) with cancer therapy completed more than 6 months prior (other than hormonal therapy) and no plan for further cancer treatments with potential risk for CTRCD.
  • Prior cancer therapy with anthracyclines and/ or HER2-targeted therapy.
  • Prior asymptomatic, moderate CTRCD, defined using the European Society of Cardiology criteria (≥10% drop in LVEF from baseline to 40% to 49.9% OR <10% drop to 40-49.9% with a reduction in GLS by >15% or new abnormal Troponin I/T or NT-proBNP), diagnosed within 1 year of completing potentially cardiotoxic cancer therapy.
  • Current use of ≥1 HF medication started for CTRCD for at least 6 months with LVEF ≥55% by recently performed (≤6 months) echocardiogram, normal NT-proBNP, and no symptoms attributable to HF.
  • Confirmation of LVEF ≥55% and normal volumes at baseline CMR (i.e., some patients recruited based on echocardiography, may be excluded if baseline CMR LVEF/volumes are not normal). This is included given that the primary outcome includes the use of CMR LVEF.

Exclusion Criteria:

  • Indication for continuation of HF medications i.e., ongoing HF symptoms, chronic kidney disease (CKD), vascular disease, atrial or ventricular arrythmias, other (note: participants with hypertension will be switched to other guideline-based antihypertensive therapy).
  • Contraindications for CMR (e.g., MRI non-compatible implanted pacemakers).
  • Patients with severe CTRCD defined as having a nadir LVEF <40% due to the known poor prognosis in these patients.
  • Continued use of loop diuretic therapy for heart failure purposes i.e., furosemide.
  • Life expectancy <1 year or metastatic disease.
  • Prior history of major cardiovascular event (defined as myocardial infarction, cerebral vascular event, admission for HF) or therapeutic cardiovascular procedure (e.g., percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG)).
  • Issues that prevent communication, understanding or presentation for study-related visits and inability to provide informed consent.

Study details

Heart Failure, Cardiotoxicity, Cardiac Toxicity, Antineoplastics Toxicity, Cancer

NCT06183437

University Health Network, Toronto

5 February 2025

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