The STOP-MED CTRCD Trial (STOP-MED CTRCD)

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

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 Overview

• Status: Recruiting
• Conditions: Heart Failure; Cancer; Cardiotoxicity; Cardiac Toxicity; Antineoplastics Toxicity
• Intervention / Treatment: Other: Stopping Heart Failure Medication(s)

• Study Type: Interventional
• Enrollment (Estimated): 335
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Paaladinesh Thavendiranathan, MD; Phone Number: 416-340-5326; Email: dinesh.thavendiranathan@uhn.ca
• Study Contact Backup: Name: Sadia Khan; Phone Number: 437-522-6441; Email: Sadia.Khan@uhn.ca

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Baker Heart and Diabetes Institute
      • Contact: Tom Marwick, MD
      • Principal Investigator: Tom Marwick, MD
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • Not yet recruiting
      • Cardio-Oncology Clinic, MAHI, University of Alberta Hospital
      • Sub-Investigator: Edith Pituskin, PhD
      • Contact: Gabor Gyenes, MD
      • Principal Investigator: Gabor Gyenes, MD
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Recruiting
      • St. Boniface Hospital
      • Contact: Davinder Jassal, MD
      • Principal Investigator: Davinder Jassal, MD
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Not yet recruiting
      • Hamilton General Hospital
      • Principal Investigator: Darryl Leong, MD
      • Contact: Darryl Leong, MD
    • Ottawa, Ontario, Canada, K1Y 4W7
      • Recruiting
      • University of Ottawa Heart Institute
      • Contact: Ian Paterson, MD
      • Principal Investigator: Ian Paterson, MD
    • Toronto, Ontario, Canada, M5G2C4
      • Recruiting
      • University Health Network
      • Contact: Paaladinesh Thavendiranathan, MD; Phone Number: 416-340-5326; Email: dinesh.thavendiranathan@uhn.ca
      • Principal Investigator: Paaladinesh Thavendiranathan, MD
    • Toronto, Ontario, Canada, M5B 1W8
      • Not yet recruiting
      • St Michael's Hospital
      • Principal Investigator: Kim Connelly, MD
      • Contact: Kim Connelly, MD
• Poland
  • Warsaw, Poland
    • Not yet recruiting
    • Maria Sklodowska-Curie National Research Institute of Oncology
    • Contact: Anna Borowiec, MD; Phone Number: 48 22 546 20 00; Email: Anna.Borowiec@nio.gov.pl
    • Principal Investigator: Anna Borowiec, MD
• Spain
  • Madrid, Spain, 28046
    • Not yet recruiting
    • La Paz University Hospital
    • Contact: Teresa Lopez Fernandez, MD; Phone Number: +34 917 27 70 00; Email: teresa.lopez@salud.madrid.org
    • Principal Investigator: Teresa Lopez Fernandez, MD
• United Kingdom
  • Liverpool, United Kingdom, L14 3PE
    • Not yet recruiting
    • Liverpool Heart and Chest Hospital
    • Contact: Rebecca Dobson, MD; Phone Number: 44 151 600 1616; Email: Rebecca.Dobson@lhch.nhs.uk
    • Principal Investigator: Rebecca Dobson, MD
  • London, United Kingdom
    • Not yet recruiting
    • Guy's and St Thomas' NHS Foundation Trust (Royal Brompton Hospital)
    • Principal Investigator: Alexander Lyon, MD
    • Contact: Alexander Lyon, MD; Phone Number: 44 20 7352 8121
    • Sub-Investigator: Siva Tharshini Ramalingam, MD
  • London
    • London, London, United Kingdom
      • Recruiting
      • Barts Health NHS Trust, University College London
      • Contact: Charlotte Manisty, MD
      • Principal Investigator: Charlotte Manisty, MD
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • University of California, Los Angeles
      • Principal Investigator: Eric Yang, MD
      • Contact: Eric Yang, MD; Phone Number: 310-825-4321; Email: EHYang@mednet.ucla.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Tomas Neilan, MD; Email: TNEILAN@mgh.harvard.edu
      • Principal Investigator: Tomas Neilan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 to severe CTRCD, defined using the ESC/ICOS criteria (MODERATE: ≥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 or SEVERE: new LVEF reduction to <40% from normal baseline LVEF), 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 sex and age adjusted NT-proBNP or BNP ≤97.5th Centile, and no symptoms attributable to HF.
• Reference ranges for NT-proBNP and BNP by age and sex:

<30 years: Female: NT-proBNP ≤196 pg/ml, BNP ≤55 pg/ml Male: NT-proBNP ≤104 pg/ml, BNP ≤29 pg/ml

30-39 years: Female: NT-proBNP ≤209 pg/ml, BNP ≤59 pg/ml Male: NT-proBNP ≤102 pg/ml, BNP ≤29 pg/ml

40-49 years: Female: NT-proBNP ≤233 pg/ml, BNP ≤65 pg/ml Male: NT-proBNP ≤137 pg/ml, BNP ≤38 pg/ml

50-59 years: Female: NT-proBNP ≤299 pg/ml, BNP ≤84 pg/ml Male: NT-proBNP ≤195 pg/ml, BNP ≤55 pg/ml

60-69 years: Female: NT-proBNP ≤399 pg/ml, BNP ≤112 pg/ml Male: NT-proBNP ≤333 pg/ml, BNP ≤93 pg/ml

70-79 years: Female: NT-proBNP ≤743 pg/ml, BNP ≤208 pg/ml Male: NT-proBNP ≤763 pg/ml, BNP ≤214 pg/ml

≥80 years: Female: NT-proBNP ≤2,704 pg/ml, BNP ≤757 pg/ml Male: NT-proBNP ≤6,792 pg/ml, BNP ≤1,902 pg/ml

• 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 cardiac devices i.e. defibrillator, CRT, pacemaker, etc.
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care Group; This group with continue with their heart failure medication(s) for at least 1 year.
Experimental: Stop Group; 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 (BB) 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. Participants on 75% of the maximal dose will be reduced to 50% of the maximal dose before reducing by 50% every 7 days. Other HF medications will be stopped as follows: MRA: reduce by 50% every 7 days then stop once 50% of maximal dose is reached; SGLT2i: stopped without titration, ARNi: reduce by 50% every 7 days then stop once 25% of the maximal dose.	Other: Stopping Heart Failure Medication(s); This group will stop their heart failure medication(s) under the supervision of the study team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cancer 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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cardiac magnetic resonance parameters	Differences between the two groups in the following measures.; Changes in CMR LVEF as a continuous parameter.; Proportion of participants with increased CMR indexed LV volumes by ≥10% to higher-than-normal limits.; Proportion of participants with decline in CMR LVEF to <50% with a >10% absolute fall compared to pre-HF medication withdrawal.; CMR peak systolic global longitudinal strain (GLS) worsening by >15%.	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.	1 year
Cost effectiveness analysis	We will compare the cost per quality adjusted life years between the two study groups.	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.	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.	1 year
Changes in quality of life score	Difference in patient questionnaires scores between the two groups using the following patient questionnaires: Kansas City Cardiomyopathy Questionnaire; Short Form (SF) Survey -36; EQ-5D-5L	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%	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.	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.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longer term changes in cardiac magnetic resonance parameters	Differences between the two groups in the following measures.; Changes in CMR LVEF as a continuous parameter.; Proportion of participants with increased CMR indexed LV volumes by ≥10% to higher-than-normal limits.; Proportion of participants with decline in CMR LVEF to <50% with a >10% absolute fall compared to pre-HF medication withdrawal.; CMR peak systolic global longitudinal strain (GLS) worsening by >15%.	5 years
Longer term changes in left ventricular diastolic function	Proportion of participants with new diastolic dysfunction or worsening diastolic function ≥1 grade by echocardiography between the two study groups.	3 and 5 years
Changes in quality of life score	Difference in patient questionnaires scores between the two groups using the following patient questionnaires: Kansas City Cardiomyopathy Questionnaire; SF-36; EQ-5D-5L	3 and
Impact of gender	Differences in the GENESIS-PRAXY score between groups	1 year
Novel biomarkers and genomic factors	Incidence of novel biomarkers and genomic factors that may determine the risk of developing the primary endpoint between the two groups.	1 year
Clinical heart failure	Difference in proportion of participants with clinical HF between the two groups.	1 year

Collaborators and Investigators

• Sponsor: Dinesh Thavendiranathan
• Collaborators: University College London Hospitals; University of California, Los Angeles; Alberta Health services; Brigham and Women's Hospital; Unity Health Toronto; Guy's and St Thomas' NHS Foundation Trust; Hamilton Health Sciences Corporation; Ottawa Heart Institute Research Corporation; Liverpool Heart and Chest Hospital NHS Foundation Trust; Hospital Universitario La Paz; St. Boniface Hospital; Maria Sklodowska-Curie National Research Institute of Oncology; Baker Heart and Diabetes Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: cancer therapy related cardiac dysfunction
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Heart Diseases; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Pathological Conditions, Signs and Symptoms; Neoplasms; Heart Failure; Cardiotoxicity; Physiological Effects of Drugs; Protective Agents; Cariostatic Agents; Tin Fluorides
• Other Study ID Numbers: STOPMED-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No