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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06183437




Registration number
NCT06183437
Ethics application status
Date submitted
13/12/2023
Date registered
27/12/2023
Date last updated
19/03/2024

Titles & IDs
Public title
The STOP-MED CTRCD Trial
Scientific 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
Secondary ID [1] 0 0
STOPMED-1
Universal Trial Number (UTN)
Trial acronym
STOP-MED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 0 0
Cardiotoxicity 0 0
Cardiac Toxicity 0 0
Antineoplastics Toxicity 0 0
Cancer 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Stopping Heart Failure Medication(s)

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 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.

No intervention: Standard of Care Group - This group with continue with their heart failure medication(s) for at least 1 year.


Other interventions: Stopping Heart Failure Medication(s)
This group will stop their heart failure medication(s) under the supervision of the study team.
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cancer Therapy Related Cardiac Dysfunction Relapse
Timepoint [1] 0 0
1 year
Secondary outcome [1] 0 0
Changes in cardiac magnetic resonance parameters
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
Left ventricular diastolic function
Timepoint [2] 0 0
1 year
Secondary outcome [3] 0 0
Non-adherence of heart failure medication(s)
Timepoint [3] 0 0
1 year
Secondary outcome [4] 0 0
N-terminal pro B-type Natriuretic Peptide (NT-pro BNP)
Timepoint [4] 0 0
1 year
Secondary outcome [5] 0 0
Changes in quality of life score
Timepoint [5] 0 0
1 year
Secondary outcome [6] 0 0
Cost effectiveness analysis
Timepoint [6] 0 0
1 year

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
4/03/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2031
Actual
Sample size
Target
335
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Baker Heart and Diabetes Institute - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
Canada
State/province [2] 0 0
Alberta
Country [3] 0 0
Canada
State/province [3] 0 0
Manitoba
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
United Kingdom
State/province [5] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
University Health Network, Toronto
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Unity Health Toronto
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Hamilton Health Sciences Corporation
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
St. Boniface Hospital
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Alberta
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
University of Ottawa Heart Institute, Canada
Address [5] 0 0
Country [5] 0 0
Other collaborator category [6] 0 0
Other
Name [6] 0 0
University College London Hospitals
Address [6] 0 0
Country [6] 0 0
Other collaborator category [7] 0 0
Other
Name [7] 0 0
Alberta Health Services, Calgary
Address [7] 0 0
Country [7] 0 0
Other collaborator category [8] 0 0
Other
Name [8] 0 0
Brigham and Women's Hospital
Address [8] 0 0
Country [8] 0 0
Other collaborator category [9] 0 0
Other
Name [9] 0 0
Baker Heart and Diabetes Institute
Address [9] 0 0
Country [9] 0 0

Ethics approval
Ethics application status

Summary
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 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.
Trial website
https://clinicaltrials.gov/study/NCT06183437
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Paaladinesh Thavendiranathan, MD
Address 0 0
Country 0 0
Phone 0 0
416-340-5326
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06183437