Clinical trial NCT06183437: The STOP-MED CTRCD Trial
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Failure
Cardiotoxicity
Cardiac Toxicity
Antineoplastics Toxicity
Cancer
Keywords: cancer therapy related cardiac dysfunction
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Unity Health Toronto
name: Hamilton Health Sciences Corporation
name: St. Boniface Hospital
name: Ottawa Heart Institute Research Corporation
name: University College London Hospitals
name: Alberta Health Services, Calgary
name: Brigham and Women's Hospital
name: Baker Heart and Diabetes Institute
First posted: 2023-12-27
Enrollment: 335
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Cancer Therapy Related Cardiac Dysfunction Relapse
timeFrame: 1 year
Secondary outcomes:
measure: Changes in cardiac magnetic resonance parameters
timeFrame: 1 year
measure: Left ventricular diastolic function
timeFrame: 1 year
measure: Non-adherence of heart failure medication(s)
timeFrame: 1 year
measure: N-terminal pro B-type Natriuretic Peptide (NT-pro BNP)
timeFrame: 1 year
measure: Changes in quality of life score
timeFrame: 1 year
measure: Cost effectiveness analysis
timeFrame: 1 year
measure: Proportion of participants developing the primary outcome by whether they developed moderate versus severe CTRCD at original diagnosis
timeFrame: 1 year
measure: Incidence of novel biomarkers and genomic factors that may determine the risk of developing the primary endpoint
timeFrame: 1 year
measure: Proportion of participants developing the primary outcome stratified by natriuretic peptides thresholds.
timeFrame: 1 year
Other outcomes:
measure: Longer term changes in cardiac magnetic resonance parameters
timeFrame: 5 years
measure: Longer term changes in left ventricular diastolic function
timeFrame: 3 and 5 years
measure: Clinical heart failure
timeFrame: 1 year
measure: Changes in quality of life score
timeFrame: 3 and
measure: Impact of gender
timeFrame: 1 year
measure: Novel biomarkers and genomic factors
timeFrame: 1 year
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Melbourne
country: Australia
facility: Baker Heart and Diabetes Institute
state: Victoria
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Edmonton
country: Canada
facility: Edmonton Clinic Health Academy
state: Alberta
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Toronto
country: Canada
facility: St Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: London
country: United Kingdom
facility: Barts Health NHS Trust, University College London
Study officials:
References: