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NCT Number: NCT06183437

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.

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Key information

Conditions

Heart Failure Antineoplastics Toxicity Cancer Cardiac Toxicity Cardiotoxicity Cardiovascular Diseases Chemically-Induced Disorders Drug-Related Side Effects and Adverse Reactions Heart Diseases Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Radiation Injuries Wounds and Injuries

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 ≥50% 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 ≥50% 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.
  • Normal Ventricular end-diastolic volumes by CMR as defined by the Society of Cardiac Magnetic Resonance 2025 update.

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 pre-CTRCD will continue their antihypertensive as only medication started for CTRCD will be ceased).
  • 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.

Treatment and study plan

Stopping Heart Failure Medication(s)

Other

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

Primary outcomes

  1. Cancer Therapy Related Cardiac Dysfunction Relapse

    Time frame: 1 year

    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.

Secondary outcomes

  1. Dichotomized Primary Outcome

    Time frame: 1 year

    The primary outcome stratified by baseline LVEF of 50-55% vs >55% .

  2. Moderate to severe CTRCD by 1 year

    Time frame: 1 year

    The development of moderate to severe asymptomatic CTRCD as per the 2022 ESC guidelines by 1 year follow-up.

  3. Changes in cardiac magnetic resonance parameters

    Time frame: 1 year

    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%.

  4. Left ventricular diastolic function

    Time frame: 1 year

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

  5. Non-adherence of heart failure medication(s)

    Time frame: 1 year

    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.

  6. N-terminal pro B-type Natriuretic Peptide (NT-pro BNP)

    Time frame: 1 year

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

  7. Changes in quality of life score

    Time frame: 1 year

    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

  8. Cost effectiveness analysis

    Time frame: 1 year

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

  9. Proportion of participants developing the primary outcome by whether they developed moderate versus severe CTRCD at original diagnosis

    Time frame: 1 year

    The proportion of those that develop the primary outcome stratified by CTRCD LVEF <40% or ≥40%

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

    Time frame: 1 year

    Incidence of cardiac, inflammatory, endothelial and other novel biomarkers and genomic factors that may determine the risk of developing the primary endpoint.

  11. Proportion of participants developing the primary outcome stratified by natriuretic peptides thresholds.

    Time frame: 1 year

    Proportion of participants developing the primary outcome stratified by natriuretic peptides thresholds.

Other outcomes

  1. Longer term changes in cardiac magnetic resonance parameters

    Time frame: 5 years

    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%.

  2. Longer term changes in left ventricular diastolic function

    Time frame: 3 and 5 years

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

  3. Clinical heart failure

    Time frame: 1 year

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

  4. Changes in quality of life score

    Time frame: 3 and

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

    • Kansas City Cardiomyopathy Questionnaire
    • SF-36
    • EQ-5D-5L

  5. Impact of gender

    Time frame: 1 year

    Differences in the GENESIS-PRAXY score between groups

  6. Novel biomarkers and genomic factors

    Time frame: 1 year

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

  7. Non-Compliance at 3 and 5 years

    Time frame: 3 years, 5 years

    Proportion of patients with non-compliance at 3 and 5 years .

  8. Primary outcome by CMR or echocardiography in each group by 3 or 5 years, stratified by baseline LVEF.

    Time frame: 3 years, 5 years

    The proportion of those that develop the primary outcome by CMR or echocardiography in each group by 3 or 5 years follow-up stratified by baseline LVEF 50-55% versus >55%.

Study contacts

Contact information is provided by the study sponsor or research team.

Paaladinesh Thavendiranathan, MD

CONTACT

[email protected]

416-340-5326

Sadia Khan

CONTACT

[email protected]

437-522-6441

Sponsors and collaborators

Lead sponsor

Dinesh Thavendiranathan

Other

Collaborators

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

Registry information

Official study title

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

Acronym: STOP-MED CTRCD

Important dates

Study start
2024
Primary completion
2027
Study completion
2031
First posted
Dec 27, 2023
Registry last updated
Jul 7, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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