The STOP-MED CTRCD Trial

Официальное название

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

Обзор

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.

Вмешательства

• Другое Stopping Heart Failure Medication(s)
  This group will stop their heart failure medication(s) under the supervision of the study team.

Первичные конечные точки

• Cancer Therapy Related Cardiac Dysfunction Relapse [Срок оценки: 1 year]

Вторичные конечные точки (11)

• Dichotomized Primary Outcome [Срок оценки: 1 year]
• Moderate to severe CTRCD by 1 year [Срок оценки: 1 year]
• Changes in cardiac magnetic resonance parameters [Срок оценки: 1 year]
• Left ventricular diastolic function [Срок оценки: 1 year]
• Non-adherence of heart failure medication(s) [Срок оценки: 1 year]
• N-terminal pro B-type Natriuretic Peptide (NT-pro BNP) [Срок оценки: 1 year]
• Changes in quality of life score [Срок оценки: 1 year]
• Cost effectiveness analysis [Срок оценки: 1 year]
• Proportion of participants developing the primary outcome by whether they developed moderate versus severe CTRCD at original diagnosis [Срок оценки: 1 year]
• Incidence of novel biomarkers and genomic factors that may determine the risk of developing the primary endpoint [Срок оценки: 1 year]
• Proportion of participants developing the primary outcome stratified by natriuretic peptides thresholds. [Срок оценки: 1 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 6 центров

• Cardio-Oncology Clinic, MAHI, University of Alberta Hospital — Edmonton
• St. Boniface Hospital — Winnipeg
• Hamilton General Hospital — Hamilton
• University of Ottawa Heart Institute — Ottawa
• St Michael's Hospital — Toronto
• University Health Network — Toronto

Великобритания · 3 центра

• Barts Health NHS Trust, University College London — London
• Liverpool Heart and Chest Hospital — Liverpool
• Guy's and St Thomas' NHS Foundation Trust (Royal Brompton Hospital) — London

США · 2 центра

• University of California, Los Angeles — Los Angeles
• Brigham and Women's Hospital — Boston

Австралия · 1 центр

• Baker Heart and Diabetes Institute — Melbourne

Польша · 1 центр

• Maria Sklodowska-Curie National Research Institute of Oncology — Warsaw

Испания · 1 центр

• La Paz University Hospital — Madrid

Идентификаторы

NCT: NCT06183437 · STOPMED-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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