Strain vs. Left Ventricular Ejection Fraction-based Cardiotoxicity Prevention in Breast Cancer

Study Overview
=================
Brief Summary
-----------------
Comparing preventive effect of myocardial global longitudinal strain-based cardioprotective stragety (angiotensin receptor blocker prophylaxis) with left ventricular ejection fraction-based strategy in breast cancer patients treated with adjuvant trastuzumab.

Detailed Description
-----------------
Despite the left ventricular global longitudinal strain (GLS) enables early prediction of trastuzumab-related cardiomyopathy, its clinical application has been hampered due to the lack of appropriate evaluation and treatment strategies. Therefore, we aimed to evaluate the effect of early intervention strategy (GLS-based cardiotoxicity monitoring and administration of candesartan) by comparing with conventional intervention strategy (left ventricular ejection fraction-based cardiotoxicity monitoring and administration of candesartan) in breast cancer patients who treated with adjuvant trastuzumab.

Official Title
-----------------
Strain-based vs. Left Ventricular Ejection Fraction-based Cardiotoxicity Prevention Strategy in Patients With Breast Cancer Who Treated With Adjuvant Trastuzumab

Conditions
-----------------
Cardiotoxicity, Breast Cancer, Prevention, Adjuvant, Trastuzumab

Intervention / Treatment
-----------------
* Drug: Candesartan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female aged ≥ 18 years Pathologically confirmed HER2-positive breast cancer Adjuvant treatment plan comprises at least 12 cycles of Trastuzumab Baseline echocardiogram should be performed before starting trastuzumab Cumulative anthracycline dose ≤ 300mg/m2 Written informed consent to participate in the study Exclusion Criteria: History of hypersensitivity or alllergic reaction to the study medication Metastatic breast cancer Treatment with angiotensin converting enzyme(ACE) inhibitor , Angiotensin receptor blocker (ARB), beta-blocking agents, or diuretics Patients with NCI/CTCAE grade ≥ 2 congestive heart failure, myocardial infarction, symptomatic left ventricular systolic dysfunction, heart's valve disease (≥ moderate), arrhythmias (Grade ≥ 3) < 12 months before enrollment Pregnancy or breast feeding Baseline systolic pressure < 90mmHg Cumulative anthracycline dose > 300mg/m2 Serious concurrent illness

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional Cardiac intervention<br>Starting candesartan in patients with left ventricular ejection fraction (LVEF) between 45% and 50% by echocardiogram. | Drug: Candesartan<br>* If GLS decreased less than 18% or LVEF decreased to 45-50% during the treatment of adjuvant trastuzumab, start candesartan medication.<br>|
| Active Comparator: Early Cardiac intervention<br>Starting candesartan in patients with decreased myocardial strain below 18% regardless of LVEF by echocardiogram. | Drug: Candesartan<br>* If GLS decreased less than 18% or LVEF decreased to 45-50% during the treatment of adjuvant trastuzumab, start candesartan medication.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular ejection fraction (LVEF) | Maximum change in LVEF | at months 3,6,9,12,18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overt chemotherapy induced cardiotoxicity | LVEF < 45%, decline in LVEF by >10% to a value to 45-49%, symptomatic congestive heart failure | any time | 
| Changes in cardiac biomarker | NT-pro BNP, cardiac troponin | at months 3,6,9,12,18 |