NCT06183437

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.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
335

participants targeted

Target at P75+ for phase_4 heart-failure

Timeline
68mo left

Started Mar 2024

Longer than P75 for phase_4 heart-failure

Geographic Reach
6 countries

14 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress28%
Mar 2024Dec 2031

First Submitted

Initial submission to the registry

December 13, 2023

Completed
14 days until next milestone

First Posted

Study publicly available on registry

December 27, 2023

Completed
2 months until next milestone

Study Start

First participant enrolled

March 4, 2024

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2027

Expected
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2031

Last Updated

March 30, 2026

Status Verified

November 1, 2025

Enrollment Period

3.7 years

First QC Date

December 13, 2023

Last Update Submit

March 25, 2026

Conditions

Heart FailureCardiotoxicityCardiac ToxicityAntineoplastics ToxicityCancer

Keywords

cancer therapy related cardiac dysfunction

Outcome Measures

Primary Outcomes (1)

  • 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% 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.

    1 year

Secondary Outcomes (9)

  • Changes in cardiac magnetic resonance parameters

    1 year

  • Left ventricular diastolic function

    1 year

  • Non-adherence of heart failure medication(s)

    1 year

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

    1 year

  • Changes in quality of life score

    1 year

  • +4 more secondary outcomes

Other Outcomes (6)

  • Longer term changes in cardiac magnetic resonance parameters

    5 years

  • Longer term changes in left ventricular diastolic function

    3 and 5 years

  • Clinical heart failure

    1 year

  • +3 more other outcomes

Study Arms (2)

Stop Group

EXPERIMENTAL

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 (BB) 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. Participants on 75% of the maximal dose will be reduced to 50% of the maximal dose before reducing by 50% every 7 days. Other HF medications will be stopped as follows: MRA: reduce by 50% every 7 days then stop once 50% of maximal dose is reached; SGLT2i: stopped without titration, ARNi: reduce by 50% every 7 days then stop once 25% of the maximal dose.

Other: Stopping Heart Failure Medication(s)

Standard of Care Group

NO INTERVENTION

This group with continue with their heart failure medication(s) for at least 1 year.

Interventions

Stopping Heart Failure Medication(s)OTHER

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

Stop Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • years: Female: NT-proBNP ≤209 pg/ml, BNP ≤59 pg/ml Male: NT-proBNP ≤102 pg/ml, BNP ≤29 pg/ml
  • years: Female: NT-proBNP ≤233 pg/ml, BNP ≤65 pg/ml Male: NT-proBNP ≤137 pg/ml, BNP ≤38 pg/ml
  • years: Female: NT-proBNP ≤299 pg/ml, BNP ≤84 pg/ml Male: NT-proBNP ≤195 pg/ml, BNP ≤55 pg/ml
  • years: Female: NT-proBNP ≤399 pg/ml, BNP ≤112 pg/ml Male: NT-proBNP ≤333 pg/ml, BNP ≤93 pg/ml
  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

University of California, Los Angeles

Los Angeles, California, 90095, United States

NOT YET RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Baker Heart and Diabetes Institute

Melbourne, Victoria, 3004, Australia

RECRUITING

Cardio-Oncology Clinic, MAHI, University of Alberta Hospital

Edmonton, Alberta, T6G 1C9, Canada

NOT YET RECRUITING

St. Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

RECRUITING

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

NOT YET RECRUITING

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

RECRUITING

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

NOT YET RECRUITING

University Health Network

Toronto, Ontario, M5G2C4, Canada

RECRUITING

Maria Sklodowska-Curie National Research Institute of Oncology

Warsaw, Poland

NOT YET RECRUITING

La Paz University Hospital

Madrid, 28046, Spain

NOT YET RECRUITING

Barts Health NHS Trust, University College London

London, London, United Kingdom

RECRUITING

Liverpool Heart and Chest Hospital

Liverpool, L14 3PE, United Kingdom

NOT YET RECRUITING

Guy's and St Thomas' NHS Foundation Trust (Royal Brompton Hospital)

London, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Heart FailureCardiotoxicityNeoplasms

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesPathologic ProcessesPathological Conditions, Signs and SymptomsDrug-Related Side Effects and Adverse ReactionsChemically-Induced DisordersRadiation InjuriesWounds and Injuries

Central Study Contacts

Paaladinesh Thavendiranathan, MD

CONTACT

416-340-5326dinesh.thavendiranathan@uhn.ca

Sadia Khan

CONTACT

437-522-6441Sadia.Khan@uhn.ca

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD, SM, FRCPC, FASE, Cardiologist, Professor of Medicine Canada Research Chair in Cardio-Oncology, Clinical Director, Echocardiography Laboratory, Director, Ted Rogers Program in Cardiotoxicity Prevention

Study Record Dates

First Submitted

December 13, 2023

First Posted

December 27, 2023

Study Start

March 4, 2024

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2031

Last Updated

March 30, 2026

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will not share

Locations

ES(1)AU(1)GB(3)US(2)CA(6)PL(1)