Prevention of cardiac dysfunction during adjuvant breast cancer treatment with anthracycline containing chemotherapy, with or without radiation or trastuzumab. MedDRA version: 20.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.1 Level: PT Classification code 10050528 Term: Ejection fraction decreased System Organ Class: 10022891 - Investigations
Conditions
Interventions
Trade Name: Entresto
Product Name: Entresto
Pharmaceutical Form: Film-coated tablet
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Sponsors
Akershus University Hospital Trust (HF)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Women with histological evidence of invasive early breast cancer scheduled for adjuvant therapy with anti-cancer regimens that include anthracyclines - Eastern Cooperative Oncology Group performance status 0-1 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 270 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - Age <18 years - Renal failure, i.e. serum creatinine greater than 133 umol/L (1,5 mg/dl) or estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 - Hyperkalemia, i.e. serum potassium greater than 5.0 mmol/L - Systolic blood pressure < 100 mg Hg - Uncontrolled hypertension - Acute myocardial infarction within the last three months - Contraindication to angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) or sacubitril/valsartan, including previous hypersensitivity reaction, angioedema and renal artery stenosis - ACEI, ARB, or aldosterone antagonist use within 4 weeks of study start - Clear indication for ACEI, ARB, or aldosterone antagonist therapy, including symptomatic heart failure - History of hemodynamically significant valvular disease - Active liver disease, i.e. alanine aminotransferase or aspartate aminotransferase greater than 1.5 times the upper limit of normal - Participation in another pharmaceutical clinical trial of an investigational medicinal product less than 4 weeks prior to inclusion or use of other investigational drugs within 5 half-lives of enrollment, whichever is longer - Psychiatric or mental disorders, alcohol abuse or other substance abuse - Language barriers or other factors which makes adherence to the study protocol difficult - Suspected poor drug compliance - Contraindication or inability to undergo CMR examination. Patients who are unable to complete the baseline CMR investigation will be excluded - Pregnancy or breastfeeding - Life expectancy < 12 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: In patients with early breast cancer scheduled for anthracycline-containing anti-cancer therapy, to assess whether the administration of Entresto can prevent or is associated with attenuation of the reduction in left ventricular systolic function measured by cardiovascular magnetic resonance (CMR);Secondary Objective: To assess whether the administration of Entresto is associated with: (1) prevention of reduction in left ventricular systolic function measured by echocardiography or CMR (2)reduced incidence of a significant reduction in left ventricular systolic function measured by CMR or echocardiography (3) reduced incidence of cardiotoxicity measured by CMR or echocardiography (4) reduced early, acute and late, chronic cardiotoxic injury measured by cardiac biomarkers;Primary end point(s): Change in left ventricular ejection fraction (LVEF), as determined by CMR from randomization to end of blinded therapy (18 months).;Timepoint(s) of evaluation of this end point: In addition to Visit 1, main scheduled visits are as following: Visit 2: at a minimum 5 days and maximum 3 weeks after completion of anthracycline containing chemotherapy but before initiation of additional therapy Visit 3: at a minimum 18 months and maximum 19 months after initiation of chemotherapy. If trastuzumab treatment exceeds this time frame, visit 3 should be at a minimum 5 days and maximum 4 weeks after completion of trastuzumab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: (1) a. Change in left ventricular ejection fraction (LVEF), as determined by echocardiography from randomization to end of blinded therapy (18 months) b. Change in GLS, as determined by echocardiography from randomization to end of blinded therapy (18 months) c. Change in end-systolic volume measured by CMR (2) Incidence of clinically significant reduction in left ventricular systolic function expressed as a. A reduction in LVEF equal or more than 5% by CMR or b. A relative percentage reduction of global longitudinal strain (GLS) > 15% (3) Incidence of cardiotoxicity expressed as: a. Reduction in LVEF ?10% to a value below 50% as measured either by CMR or Echocardiography or b. Incidence of clinical heart failure (4) Cardiotoxic injury expressed as change in circulating concentrations of cardiac troponins I and T measured by high sensitivity assays (hs-TnI and hs-TnT) and N-terminal proB-type natriuretic peptide (NT-proBNP) ;Timepoint(s) of evaluation of this end point: In addition to Visit 1, main scheduled visits are as following: Visit 2: at a minimum 5 days and maximum 3 weeks after completion of anthracycline containing chemotherapy but before initiation of additional therapy Visit 3: at a minimum 18 months and maximum 19 months after initiation of chemotherapy. If trastuzumab treatment exceeds this time frame, visit 3 should be at a minimum 5 days and maximum 4 weeks after completion of trastuzumab | — |
Countries
Norway
Contacts
Public ContactTorbjørn Omland
Akershus University Hospital Trust (HF)
Outcome results
None listed