The STOP-MED CTRCD Trial

Cancer Clinical Trial

— STOP-MED  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06183437
• Other study ID #: STOPMED-1
• Status: Recruiting
• Phase: Phase 4
• Start date: March 4, 2024
• Est. completion date: December 2031

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: Paaladinesh Thavendiranathan, MD
• Phone: 416-340-5326
• Email: dinesh.thavendiranathan[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 335
• Est. completion date: December 2031
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Cancer
• Cardiac Toxicity
• Cardiotoxicity
• Heart Failure

Intervention

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

Locations

Country	Name	City	State
Australia	Baker Heart and Diabetes Institute	Melbourne	Victoria
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Edmonton Clinic Health Academy	Edmonton	Alberta
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	St Michael's Hospital	Toronto	Ontario
Canada	University Health Network	Toronto	Ontario
Canada	St. Boniface Hospital	Winnipeg	Manitoba
United Kingdom	University College London	London
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (10)

Lead Sponsor	Collaborator
University Health Network, Toronto	Alberta Health Services, Calgary, Baker Heart and Diabetes Institute, Brigham and Women's Hospital, Hamilton Health Sciences Corporation, St. Boniface Hospital, Unity Health Toronto, University College London Hospitals, University of Alberta, University of Ottawa Heart Institute, Canada

Countries where clinical trial is conducted

United States,  Australia,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Clinical heart failure	Difference in proportion of participants with clinical HF between the two groups.	1 year
Other	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
Other	Impact of gender	Differences in the GENESIS-PRAXY score between groups	1 year
Other	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
Primary	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% 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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cost effectiveness analysis	We will compare the cost per quality adjusted life years between the two study groups.	1 year