Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial.
Mateusz Tajstra, Maciej Dyrbuś, Tomasz Rutkowski...
https://pubmed.ncbi.nlm.nih.gov/37449716Actively Recruiting
Phase 4
Age: 18Years +
FEMALE
ID05465031
Sacubitril/Valsartan in Primary Prevention of Cardiotoxicity During Systematic Breast Cancer Treatment
Led by Silesian Centre for Heart Diseases · Updated on 2025-03-14
600
Participants Needed
4
Research Sites
61 weeks
Total Duration
On this page
Sponsors
S
Silesian Centre for Heart Diseases
Lead Sponsor
M
Medical Research Agency, Poland
Collaborating Sponsor
AI-Summary
What this Trial Is About
Breast cancer is the most common cancer among women worldwide, with over 2.25 million new cases reported in 2020. While modern treatments like surgery, radiotherapy, hormone therapy, and targeted chemotherapy have improved survival, they often lead to cardiotoxicity, which can cause heart failure or reduced heart function. This trial evaluates whether sacubitril/valsartan, a drug used for heart failure, can prevent cardiotoxicity in breast cancer patients receiving chemotherapy, particularly with anthracyclines or HER-2 targeted therapies. The study is a randomized, double-blind, placebo-controlled trial involving 480 women with confirmed breast cancer eligible for chemotherapy with anthracyclines and/or HER-2 monoclonal antibodies. Participants first undergo a single-blind phase to test drug tolerance, then are randomly assigned to receive either sacubitril/valsartan or placebo for up to 24 months. The sacubitril/valsartan dose starts at 100 mg twice daily, increasing to a target dose of 200 mg twice daily if tolerated. Study drug doses may be adjusted based on patient tolerance. Standard breast cancer treatments continue alongside the study intervention. Participants will have multiple study visits at 3, 12, and 24 months post-randomization. These visits include heart function assessments with echocardiography, optional MRI scans, electrocardiograms including 24-hour Holter monitoring, blood tests including cardiac biomarkers, functional capacity tests, and quality of life questionnaires. The main outcome is the change in left ventricular ejection fraction over 24 months. Safety and other heart-related events will also be monitored. Genetic testing may be performed to explore individual responses to the drug. The study lasts up to 24 months with ongoing follow-up and monitoring.
CONDITIONS
Brief Title
Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)
Who Can Participate
Age: 18Years +
FEMALE
Eligibility Criteria
You may qualify if you...
- Written informed consent
- Female gender, aged 18 years and over
- Histologically confirmed breast cancer with full tumor phenotype assessment
- Ability to take oral medication and follow the study plan
- Tumor stage IA-IIIC or oligometastatic IV
- Planned radical treatment including surgery
- Planned systemic treatment with anthracyclines and/or anti-HER2 drugs
- Eastern Cooperative Oncology Group (ECOG) status 0-2
- Left ventricular ejection fraction (LVEF) of 50% or higher
- Sinus heart rhythm
You will not qualify if you...
- Prior anthracycline chemotherapy or thoracic radiotherapy before current cancer diagnosis
- Clinically relevant heart failure (NYHA II-IV)
- Myocardial infarction within the last less than 3 months
- Symptomatic low blood pressure or systolic blood pressure below 90 mmHg
- Significant valve disease, symptomatic coronary artery disease, advanced AV block, or symptomatic sinus node dysfunction
- Expected survival less than 12 months
- Kidney function with GFR below 30 ml/min/1.73 m2
- Potassium level higher than 5.5 mmol/L
- Contraindications to ACE inhibitors, ARBs, or sacubitril/valsartan
- Active untreated liver disease
- Pregnancy
- Conditions likely to cause non-compliance, such as active substance dependence or poorly controlled mental illness
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 screening and enrollment visit
Run-in Period
Duration - Approximately 2 weeks
Participants begin single-blinded treatment with sacubitril/valsartan at a starting dose which is uptitrated to the target dose, to assess tolerance before randomization.
2 visits (1 initial and 1 run-in visit about 6-8 days later)
Treatment
Duration - Up to 24 months
Participants are randomized to receive either sacubitril/valsartan or placebo at the target dose for up to 24 months, with dose adjustments if necessary based on tolerance.
3 visits at 3 months, 12 months, and 24 months after randomization
Trial Site Locations
Total: 4 locations
1
Regional Cancer Centre in Opole
Opole, Opole Voivodeship, Poland, 45-061
Actively Recruiting
2
Maria Sklodowska-Curie Institute - Oncology Centre (MSCI), Gliwice Branch
Gliwice, Silesian Voivodeship, Poland, 44102
Actively Recruiting
3
Silesian Center for Heart Diseases
Zabrze, Silesian Voivodeship, Poland, 41800
Active, Not Recruiting
4
Holy Cross Cancer Centre, Cardio-Oncology Division
Kielce, Świętokrzyskie Voivodeship, Poland, 25-734
Actively Recruiting
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Research Team
M
Mateusz Tajstra, MD, PhD, Assoc Prof
L
Lucyna Broja
How is the study designed?
Study Type
INTERVENTIONAL
Masking
TRIPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
PREVENTION
Number of Arms
2
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