{
    "info": {
        "nct_id": "NCT00391690",
        "official_title": "Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer",
        "inclusion_criteria": "Healthy volunteers allowed\nMust be MALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "",
        "miscellaneous_criteria": "Inclusion criteria:\n\n* Patients with histologically confirmed diagnosis of prostate cancer who have not yet developed bone metastases\n* Prostate cancer patients with a rise in PSA under hormone therapy.\n\nPSA criteria:\n\n* Patients who have undergone prostatectomy: any rise in PSA or\n* Patients without prostatectomy: 2 consecutive rises in PSA levels relative to a previous reference value, separated by one month. The first measurement must occur one month after the reference value and must be above the reference value. The second confirmatory measurement taken one month after the first measurement must be greater than the first measurement.\n* Previous chemotherapy or radiotherapy must have been performed ≥ 8 weeks prior to study entry.\n* Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 (patients that spend less than 50% of time in bed during the day)\n* Adequate liver function - serum total bilirubin concentration less than 1.5 x upper limit of normal value\n* Age: ≥ 18 years\n* Patient has given written informed consent prior to any study-specific procedures. Patients with psychiatric or addictive disorders which prevent them from giving their informed consent must not enter the study.\n\nExclusion criteria:\n\n* Prior treatment with a bisphosphonate\n* Abnormal renal function as evidenced by a calculated creatinine clearance < 30 ml/minute.\n* Corrected (adjusted for serum albumin) serum calcium concentration < 8.0 mg/dl (2.00 mmol/L) or ≥ 12.0 mg/dl (3.00 mmol/L).\n* Patients with clinically symptomatic brain metastases\n* History of diseases with influence on bone metabolism such as Paget's disease and primary hyperparathyroidism\n* Severe physical or psychological concomitant diseases that might impair compliance with the provisions of the study protocol or that might impair the assessment of drug or patient safety, e.g. clinically significant ascites, cardiac failure, NYHA III or IV, clinically relevant pathologic findings in ECG\n* Known hypersensitivity to zoledronic acid or other bisphosphonates\n* Use of other investigational drugs 30 days prior to the date of randomization\n* Known history or present abuse of alcohol or drugs\n* Subjects who, in the opinion of the investigator, are unlikely to cooperate fully during the study\n* Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.\n* Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)\n\nOther protocol defined inclusion/exclusion criteria may apply."
    },
    "inclusion_lines": [
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": [
                        "Healthy volunteers allowed"
                    ],
                    "criterion": "healthy volunteers",
                    "requirement_type": "participation",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Must be MALE",
            "criterions": [
                {
                    "exact_snippets": [
                        "Must be MALE"
                    ],
                    "criterion": "gender",
                    "requirement_type": "specific value",
                    "expected_value": "male"
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": [
                        "minimum age of 18 Years"
                    ],
                    "criterion": "age",
                    "requirement_type": "minimum",
                    "expected_value": {
                        "operator": ">=",
                        "value": 18
                    }
                }
            ]
        }
    ],
    "exclusion_lines": [],
    "miscellaneous_lines": [
        {
            "line": "* Patients with histologically confirmed diagnosis of prostate cancer who have not yet developed bone metastases",
            "criterions": [
                {
                    "exact_snippets": [
                        "histologically confirmed diagnosis of prostate cancer"
                    ],
                    "criterion": "prostate cancer",
                    "requirement_type": "diagnosis confirmation",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "have not yet developed bone metastases"
                    ],
                    "criterion": "bone metastases",
                    "requirement_type": "presence",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Prostate cancer patients with a rise in PSA under hormone therapy.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Prostate cancer patients"
                    ],
                    "criterion": "prostate cancer",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "a rise in PSA"
                    ],
                    "criterion": "PSA",
                    "requirement_type": "trend",
                    "expected_value": "rise"
                },
                {
                    "exact_snippets": [
                        "under hormone therapy"
                    ],
                    "criterion": "hormone therapy",
                    "requirement_type": "current treatment",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "PSA criteria:",
            "criterions": [
                {
                    "exact_snippets": [
                        "PSA criteria"
                    ],
                    "criterion": "PSA",
                    "requirement_type": "N/A",
                    "expected_value": "criteria"
                }
            ]
        },
        {
            "line": "* Patients who have undergone prostatectomy: any rise in PSA or",
            "criterions": [
                {
                    "exact_snippets": [
                        "undergone prostatectomy"
                    ],
                    "criterion": "prostatectomy",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "rise in PSA"
                    ],
                    "criterion": "PSA",
                    "requirement_type": "change",
                    "expected_value": "rise"
                }
            ]
        },
        {
            "line": "* Patients without prostatectomy: 2 consecutive rises in PSA levels relative to a previous reference value, separated by one month. The first measurement must occur one month after the reference value and must be above the reference value. The second confirmatory measurement taken one month after the first measurement must be greater than the first measurement.",
            "criterions": [
                {
                    "exact_snippets": [
                        "without prostatectomy"
                    ],
                    "criterion": "prostatectomy",
                    "requirement_type": "absence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "2 consecutive rises in PSA levels"
                    ],
                    "criterion": "PSA levels",
                    "requirement_type": "trend",
                    "expected_value": "2 consecutive rises"
                },
                {
                    "exact_snippets": [
                        "relative to a previous reference value"
                    ],
                    "criterion": "PSA levels",
                    "requirement_type": "comparison to reference",
                    "expected_value": "relative to a previous reference value"
                },
                {
                    "exact_snippets": [
                        "The first measurement must occur one month after the reference value"
                    ],
                    "criterion": "PSA levels",
                    "requirement_type": "timing",
                    "expected_value": "one month after the reference value"
                },
                {
                    "exact_snippets": [
                        "must be above the reference value"
                    ],
                    "criterion": "PSA levels",
                    "requirement_type": "comparison to reference",
                    "expected_value": "above the reference value"
                },
                {
                    "exact_snippets": [
                        "The second confirmatory measurement taken one month after the first measurement"
                    ],
                    "criterion": "PSA levels",
                    "requirement_type": "timing",
                    "expected_value": "one month after the first measurement"
                },
                {
                    "exact_snippets": [
                        "must be greater than the first measurement"
                    ],
                    "criterion": "PSA levels",
                    "requirement_type": "comparison to previous",
                    "expected_value": "greater than the first measurement"
                }
            ]
        },
        {
            "line": "* Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 (patients that spend less than 50% of time in bed during the day)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2"
                    ],
                    "criterion": "ECOG score",
                    "requirement_type": "range",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 0
                            },
                            {
                                "operator": "<=",
                                "value": 2
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Adequate liver function - serum total bilirubin concentration less than 1.5 x upper limit of normal value",
            "criterions": [
                {
                    "exact_snippets": [
                        "Adequate liver function"
                    ],
                    "criterion": "liver function",
                    "requirement_type": "adequacy",
                    "expected_value": "adequate"
                },
                {
                    "exact_snippets": [
                        "serum total bilirubin concentration",
                        "less than 1.5 x upper limit of normal value"
                    ],
                    "criterion": "serum total bilirubin concentration",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 1.5
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Age: ≥ 18 years",
            "criterions": [
                {
                    "exact_snippets": [
                        "Age: ≥ 18 years"
                    ],
                    "criterion": "age",
                    "requirement_type": "N/A",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 18
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Patient has given written informed consent prior to any study-specific procedures. Patients with psychiatric or addictive disorders which prevent them from giving their informed consent must not enter the study.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Patient has given written informed consent"
                    ],
                    "criterion": "informed consent",
                    "requirement_type": "given",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Patients with psychiatric or addictive disorders"
                    ],
                    "criterion": "psychiatric or addictive disorders",
                    "requirement_type": "presence",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Prior treatment with a bisphosphonate",
            "criterions": [
                {
                    "exact_snippets": [
                        "Prior treatment with a bisphosphonate"
                    ],
                    "criterion": "bisphosphonate treatment",
                    "requirement_type": "prior",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Abnormal renal function as evidenced by a calculated creatinine clearance < 30 ml/minute.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Abnormal renal function",
                        "calculated creatinine clearance < 30 ml/minute"
                    ],
                    "criterion": "renal function",
                    "requirement_type": "abnormality",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "calculated creatinine clearance < 30 ml/minute"
                    ],
                    "criterion": "creatinine clearance",
                    "requirement_type": "quantity",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 30
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Corrected (adjusted for serum albumin) serum calcium concentration < 8.0 mg/dl (2.00 mmol/L) or ≥ 12.0 mg/dl (3.00 mmol/L).",
            "criterions": [
                {
                    "exact_snippets": [
                        "Corrected (adjusted for serum albumin) serum calcium concentration",
                        "< 8.0 mg/dl (2.00 mmol/L)"
                    ],
                    "criterion": "corrected serum calcium concentration",
                    "requirement_type": "range",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<",
                                "value": 8.0
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Corrected (adjusted for serum albumin) serum calcium concentration",
                        "≥ 12.0 mg/dl (3.00 mmol/L)"
                    ],
                    "criterion": "corrected serum calcium concentration",
                    "requirement_type": "range",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 12.0
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Patients with clinically symptomatic brain metastases",
            "criterions": [
                {
                    "exact_snippets": [
                        "clinically symptomatic brain metastases"
                    ],
                    "criterion": "brain metastases",
                    "requirement_type": "symptom presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* History of diseases with influence on bone metabolism such as Paget's disease and primary hyperparathyroidism",
            "criterions": [
                {
                    "exact_snippets": [
                        "History of diseases with influence on bone metabolism"
                    ],
                    "criterion": "diseases with influence on bone metabolism",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Paget's disease"
                    ],
                    "criterion": "Paget's disease",
                    "requirement_type": "history",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "primary hyperparathyroidism"
                    ],
                    "criterion": "primary hyperparathyroidism",
                    "requirement_type": "history",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Severe physical or psychological concomitant diseases that might impair compliance with the provisions of the study protocol or that might impair the assessment of drug or patient safety, e.g. clinically significant ascites, cardiac failure, NYHA III or IV, clinically relevant pathologic findings in ECG",
            "criterions": [
                {
                    "exact_snippets": [
                        "Severe physical or psychological concomitant diseases"
                    ],
                    "criterion": "concomitant diseases",
                    "requirement_type": "severity",
                    "expected_value": "severe"
                },
                {
                    "exact_snippets": [
                        "compliance with the provisions of the study protocol"
                    ],
                    "criterion": "compliance with study protocol",
                    "requirement_type": "impairment",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "assessment of drug or patient safety"
                    ],
                    "criterion": "assessment of drug or patient safety",
                    "requirement_type": "impairment",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "clinically significant ascites"
                    ],
                    "criterion": "ascites",
                    "requirement_type": "clinical significance",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "cardiac failure, NYHA III or IV"
                    ],
                    "criterion": "cardiac failure",
                    "requirement_type": "NYHA classification",
                    "expected_value": [
                        "III",
                        "IV"
                    ]
                },
                {
                    "exact_snippets": [
                        "clinically relevant pathologic findings in ECG"
                    ],
                    "criterion": "pathologic findings in ECG",
                    "requirement_type": "clinical relevance",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Known hypersensitivity to zoledronic acid or other bisphosphonates",
            "criterions": [
                {
                    "exact_snippets": [
                        "Known hypersensitivity to zoledronic acid"
                    ],
                    "criterion": "hypersensitivity",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "hypersensitivity to",
                        "other bisphosphonates"
                    ],
                    "criterion": "hypersensitivity",
                    "requirement_type": "presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Use of other investigational drugs 30 days prior to the date of randomization",
            "criterions": [
                {
                    "exact_snippets": [
                        "Use of other investigational drugs 30 days prior to the date of randomization"
                    ],
                    "criterion": "use of investigational drugs",
                    "requirement_type": "time frame",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 30
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "* Known history or present abuse of alcohol or drugs",
            "criterions": [
                {
                    "exact_snippets": [
                        "Known history or present abuse of alcohol"
                    ],
                    "criterion": "alcohol abuse",
                    "requirement_type": "history or presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "Known history or present abuse of",
                        "drugs"
                    ],
                    "criterion": "drug abuse",
                    "requirement_type": "history or presence",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "* Subjects who, in the opinion of the investigator, are unlikely to cooperate fully during the study",
            "criterions": [
                {
                    "exact_snippets": [
                        "unlikely to cooperate fully during the study"
                    ],
                    "criterion": "cooperation",
                    "requirement_type": "likelihood",
                    "expected_value": false
                }
            ]
        },
        {
            "line": "* Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Current active dental problems"
                    ],
                    "criterion": "dental problems",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "infection of the teeth or jawbone"
                    ],
                    "criterion": "infection",
                    "requirement_type": "location",
                    "expected_value": [
                        "teeth",
                        "jawbone"
                    ]
                },
                {
                    "exact_snippets": [
                        "dental or fixture trauma"
                    ],
                    "criterion": "trauma",
                    "requirement_type": "presence",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "current or prior diagnosis of osteonecrosis of the jaw (ONJ)"
                    ],
                    "criterion": "osteonecrosis of the jaw (ONJ)",
                    "requirement_type": "diagnosis",
                    "expected_value": true
                },
                {
                    "exact_snippets": [
                        "exposed bone in the mouth"
                    ],
                    "criterion": "exposed bone",
                    "requirement_type": "location",
                    "expected_value": "mouth"
                },
                {
                    "exact_snippets": [
                        "slow healing after dental procedures"
                    ],
                    "criterion": "healing",
                    "requirement_type": "speed",
                    "expected_value": "slow"
                }
            ]
        },
        {
            "line": "* Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants)",
            "criterions": [
                {
                    "exact_snippets": [
                        "Recent (within 6 weeks) or planned dental or jaw surgery"
                    ],
                    "criterion": "dental or jaw surgery",
                    "requirement_type": "recency",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": "<=",
                                "value": 6
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "planned dental or jaw surgery"
                    ],
                    "criterion": "dental or jaw surgery",
                    "requirement_type": "planned",
                    "expected_value": true
                }
            ]
        },
        {
            "line": "Other protocol defined inclusion/exclusion criteria may apply.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Other protocol defined inclusion/exclusion criteria"
                    ],
                    "criterion": "protocol defined criteria",
                    "requirement_type": "inclusion/exclusion",
                    "expected_value": "may apply"
                }
            ]
        }
    ],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": [
        {
            "line": "Inclusion criteria:",
            "criterions": []
        },
        {
            "line": "* Previous chemotherapy or radiotherapy must have been performed ≥ 8 weeks prior to study entry.",
            "criterions": [
                {
                    "exact_snippets": [
                        "Previous chemotherapy"
                    ],
                    "criterion": "chemotherapy",
                    "requirement_type": "timing",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 8
                            }
                        ]
                    }
                },
                {
                    "exact_snippets": [
                        "Previous radiotherapy"
                    ],
                    "criterion": "radiotherapy",
                    "requirement_type": "timing",
                    "expected_value": {
                        "comparisons": [
                            {
                                "operator": ">=",
                                "value": 8
                            }
                        ]
                    }
                }
            ]
        },
        {
            "line": "Exclusion criteria:",
            "criterions": []
        }
    ]
}