{
    "info": {
        "nct_id": "NCT05465031",
        "official_title": "Sacubitril/Valsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent",
        "inclusion_criteria": "* Written informed consent\n* Female gender, aged 18 years and over\n* Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (ER, PR, HER2, Ki67)\n* Ability to take oral medication and willingness to adhere to the planned regimen\n* Tumor grade IA-IIIC or oligometastatic grade IV\n* Radical treatment plan including surgery\n* Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and/or anti-HER2 drugs\n* ECOG 0-2 general status\n* LVEF ≥ 50% as assessed by echocardiography\n* Sinus rhythm\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* Prior anthracycline-based chemotherapy and/or left-sided radiotherapy (prior to diagnosis of the cancer being the present cause of therapy)\n* Clinically relevant HF (NYHA II-IV)\n* MI within the last < 3 months\n* Symptomatic hypotension or SBP < 90 mmHg\n* Significant valvular disease, symptomatic coronary artery disease (CCS>2), significant AV block, symptomatic sinus node dysfunction\n* Expected survival <12 months\n* GFR<30 ml/min/1.73 m2 (screening visit)\n* K+>5.5mmol/L (screening visit)\n* Contraindications to ACE-I/ARB or LCZ696 if not listed among criteria\n* Active untreated liver disease\n* Pregnancy\n* Contraindications to cardiac MRI, including allergy to gadolinium-containing contrast agent or presence of implanted materials or devices prohibited for MRI\n* Conditions/circumstances that may lead to non-compliance with medical staff recommendations (e.g. active drug/alcohol dependence, poorly controlled mental illness)",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Written informed consent",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Female gender, aged 18 years and over",
            "criterions": [
                {
                    "exact_snippets": "Female gender",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": "female"
                        }
                    ]
                },
                {
                    "exact_snippets": "aged 18 years and over",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (ER, PR, HER2, Ki67)",
            "criterions": [
                {
                    "exact_snippets": "histologically confirmed breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "histologically confirmed"
                        }
                    ]
                },
                {
                    "exact_snippets": "complete assessment of tumor phenotype (ER, PR, HER2, Ki67)",
                    "criterion": "tumor phenotype assessment",
                    "requirements": [
                        {
                            "requirement_type": "completeness",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "components",
                            "expected_value": [
                                "ER",
                                "PR",
                                "HER2",
                                "Ki67"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Ability to take oral medication and willingness to adhere to the planned regimen",
            "criterions": [
                {
                    "exact_snippets": "Ability to take oral medication",
                    "criterion": "ability to take oral medication",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "willingness to adhere to the planned regimen",
                    "criterion": "willingness to adhere to the planned regimen",
                    "requirements": [
                        {
                            "requirement_type": "willingness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Tumor grade IA-IIIC or oligometastatic grade IV",
            "criterions": [
                {
                    "exact_snippets": "Tumor grade IA-IIIC",
                    "criterion": "tumor grade",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 1,
                                        "unit": "A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 3,
                                        "unit": "C"
                                    }
                                ]
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "oligometastatic grade IV",
                    "criterion": "tumor grade",
                    "requirements": [
                        {
                            "requirement_type": "specific",
                            "expected_value": "oligometastatic grade IV"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Radical treatment plan including surgery",
            "criterions": [
                {
                    "exact_snippets": "Radical treatment plan including surgery",
                    "criterion": "treatment plan",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "radical"
                        },
                        {
                            "requirement_type": "inclusion",
                            "expected_value": "surgery"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and/or anti-HER2 drugs",
            "criterions": [
                {
                    "exact_snippets": "use of systemic treatment ... with anthracyclines",
                    "criterion": "systemic treatment with anthracyclines",
                    "requirements": [
                        {
                            "requirement_type": "plan",
                            "expected_value": [
                                "preoperative",
                                "postoperative",
                                "combined"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "use of systemic treatment ... with ... anti-HER2 drugs",
                    "criterion": "systemic treatment with anti-HER2 drugs",
                    "requirements": [
                        {
                            "requirement_type": "plan",
                            "expected_value": [
                                "preoperative",
                                "postoperative",
                                "combined"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* ECOG 0-2 general status",
            "criterions": [
                {
                    "exact_snippets": "ECOG 0-2 general status",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* LVEF ≥ 50% as assessed by echocardiography",
            "criterions": [
                {
                    "exact_snippets": "LVEF ≥ 50% as assessed by echocardiography",
                    "criterion": "LVEF",
                    "requirements": [
                        {
                            "requirement_type": "assessment method",
                            "expected_value": "echocardiography"
                        },
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Sinus rhythm",
            "criterions": [
                {
                    "exact_snippets": "Sinus rhythm",
                    "criterion": "sinus rhythm",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "healthy volunteers",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must be FEMALE",
            "criterions": [
                {
                    "exact_snippets": "Must be FEMALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* Prior anthracycline-based chemotherapy and/or left-sided radiotherapy (prior to diagnosis of the cancer being the present cause of therapy)",
            "criterions": [
                {
                    "exact_snippets": "Prior anthracycline-based chemotherapy",
                    "criterion": "prior anthracycline-based chemotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "left-sided radiotherapy (prior to diagnosis of the cancer being the present cause of therapy)",
                    "criterion": "left-sided radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Clinically relevant HF (NYHA II-IV)",
            "criterions": [
                {
                    "exact_snippets": "Clinically relevant HF (NYHA II-IV)",
                    "criterion": "heart failure",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 2,
                                        "unit": "NYHA"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 4,
                                        "unit": "NYHA"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* MI within the last < 3 months",
            "criterions": [
                {
                    "exact_snippets": "MI within the last < 3 months",
                    "criterion": "myocardial infarction (MI)",
                    "requirements": [
                        {
                            "requirement_type": "time since occurrence",
                            "expected_value": {
                                "operator": "<",
                                "value": 3,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Symptomatic hypotension or SBP < 90 mmHg",
            "criterions": [
                {
                    "exact_snippets": "Symptomatic hypotension",
                    "criterion": "hypotension",
                    "requirements": [
                        {
                            "requirement_type": "symptomatic",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "SBP < 90 mmHg",
                    "criterion": "systolic blood pressure (SBP)",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": "<",
                                "value": 90,
                                "unit": "mmHg"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Significant valvular disease, symptomatic coronary artery disease (CCS>2), significant AV block, symptomatic sinus node dysfunction",
            "criterions": [
                {
                    "exact_snippets": "Significant valvular disease",
                    "criterion": "valvular disease",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "symptomatic coronary artery disease (CCS>2)",
                    "criterion": "coronary artery disease",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "CCS score",
                            "expected_value": {
                                "operator": ">",
                                "value": 2,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "significant AV block",
                    "criterion": "AV block",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "symptomatic sinus node dysfunction",
                    "criterion": "sinus node dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Expected survival <12 months",
            "criterions": [
                {
                    "exact_snippets": "Expected survival <12 months",
                    "criterion": "expected survival",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": {
                                "operator": "<",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* GFR<30 ml/min/1.73 m2 (screening visit)",
            "criterions": [
                {
                    "exact_snippets": "GFR<30 ml/min/1.73 m2",
                    "criterion": "GFR",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": "<",
                                "value": 30,
                                "unit": "ml/min/1.73 m2"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* K+>5.5mmol/L (screening visit)",
            "criterions": [
                {
                    "exact_snippets": "K+>5.5mmol/L",
                    "criterion": "potassium level",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": ">",
                                "value": 5.5,
                                "unit": "mmol/L"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Contraindications to ACE-I/ARB or LCZ696 if not listed among criteria",
            "criterions": [
                {
                    "exact_snippets": "Contraindications to ACE-I/ARB or LCZ696",
                    "criterion": "contraindications",
                    "requirements": [
                        {
                            "requirement_type": "medications",
                            "expected_value": [
                                "ACE-I",
                                "ARB",
                                "LCZ696"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Active untreated liver disease",
            "criterions": [
                {
                    "exact_snippets": "Active untreated liver disease",
                    "criterion": "liver disease",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        },
                        {
                            "requirement_type": "treatment",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnancy",
            "criterions": [
                {
                    "exact_snippets": "Pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Contraindications to cardiac MRI, including allergy to gadolinium-containing contrast agent or presence of implanted materials or devices prohibited for MRI",
            "criterions": [
                {
                    "exact_snippets": "Contraindications to cardiac MRI",
                    "criterion": "cardiac MRI contraindications",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "allergy to gadolinium-containing contrast agent",
                    "criterion": "allergy to gadolinium-containing contrast agent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "presence of implanted materials or devices prohibited for MRI",
                    "criterion": "implanted materials or devices prohibited for MRI",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Conditions/circumstances that may lead to non-compliance with medical staff recommendations (e.g. active drug/alcohol dependence, poorly controlled mental illness)",
            "criterions": [
                {
                    "exact_snippets": "active drug/alcohol dependence",
                    "criterion": "drug/alcohol dependence",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "active"
                        }
                    ]
                },
                {
                    "exact_snippets": "poorly controlled mental illness",
                    "criterion": "mental illness",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": "poorly controlled"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}