Heart failure – post-anthracycline cardiomyopathy MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Trade Name: Entresto 49 mg/51 mg
Product Name: Entresto 49mg/51mg
Pharmaceutical Form: Coated tablet
INN or Proposed INN: sacubitril
Other descriptive name: Sacubitril valsartan sodium hydrate
Conce
Sponsors
Slaskie Centrum Chorób Serca
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Female gender, aged 18 years and over 3. Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (ER, PR, HER2, Ki67) 4. Ability to take oral medication and willingness to adhere to the planned regimen 5. Tumor grade IA-IIIC or oligometastatic grade IV 6. Radical treatment plan including surgery or post-radical surgical treatment 7. Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and/or anti-HER2 drugs 8. ECOG 0-2 general status 9. LVEF = 50% as assessed by echocardiography 10. Sinus rhythm Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: 1. Lack of Written informed consent 2. Prior anthracycline-based chemotherapy and/or left-sided radiotherapy (prior to diagnosis of the cancer being the present cause of therapy) 3. Clinically relevant HF (NYHA II-IV) 4. MI within the last 2), significant AV block, symptomatic sinus node dysfunction 7. Expected survival 5.5mmol/L (screening visit) 10. Contraindications to ACE-I/ARB or LCZ696 if not listed among criteria 11. Active untreated liver disease 12. Pregnancy 13. Conditions/circumstances that may lead to non-compliance with medical staff recommendations (e.g. active drug/alcohol dependence, poorly controlled mental illness)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Estimation of whether prophylactic use of sacubitril/valsartan will prevent cardiotoxicity associated with systemic breast cancer treatment, defined as a decrease in left ventricular ejection fraction = 5% in an ultrasound scan during 24 months from randomization.;Secondary Objective: Estimation of whether NT-proBNP and troponin markers can be used as indicators of the prevention of cardiotoxicity associated with systemic treatment of sacubitril/valsartan breast cancer. Estimation of genetic correlation with prevention of cardiotoxicity associated with systemic treatment of breast cancer with sacubitril/valsartan. Estimation of the reversibility of cardiotoxicity associated with systemic breast cancer treatment defined as a decrease in left ventricular ejection fraction. Comparison of the detection sensitivity of cardiotoxicity associated with systemic treatment of breast cancer defined as a decrease in LVEF = 5% in ultrasound examination with other imaging tests – ultrasound of the heart (UKG-echocardiography) Estimation of the role of novel markers of cardiotoxicity (myeloperoxidase (MPO), galectin 3, GDF-15 protein and circulating receptor for IL-33 (sST2), but other considered biomarkers (PIGF, suPAR) and potential genomic markers (microRNAs) ;Primary end point(s): Decrease in left ventricular ejection fraction = 5% assessed on magnetic resonance imaging (MRI) in 24 months from randomisation;Timepoint(s) of evaluation of this end point: 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Death from any cause or hospitalization for heart failure 2. Death from any cause 3. Death from cardiovascular causes 4. Hospitalization for other cardiovascular causes 5. cardiotoxicity 6. Decrease in left ventricular ejection fraction = 5% (MRI) during 24 months from randomization 7. Decrease in left ventricular ejection fraction = 5% during 24 months from randomization 8. Occurrence of diastolic dysfunction (UKG) within 24 months of randomization Diastolic dysfunction assessed on echocardiography 9. Development of pathological pericardial fluid volume or increase in pericardial fluid volume from baseline 10. Occurrence of cardiac tamponade 11. Occurrence of pericarditis 12. Occurrence of myocarditis 13. Development of ventricular arrhythmias 14. Development of supraventricular arrhythmias 15. Presence of conduction disturbances 16. Changes in corrected QT interval 17. Changes in BNP, NT pro-BNP, troponin T or troponin I levels ;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Poland
Contacts
Public ContactKoordynator Krajowy
Dr hab. n. med. Mateusz Tajstra / Slaskie Centrum Chorób Serca w Zabrzu
Outcome results
None listed