A Trial of Telmisartan Prevention of Cardiovascular Disease

Study Overview
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Brief Summary
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The present research is conducted as a randomized, parallel-group, controlled, open study (using the PROBE method) to primarily verify the effects on various biomarkers in high-risk hypertensive patients treated with ARB (telmisartan, ARB group) as compared with those in patients receiving ordinary therapy (non-ARB group (ordinary therapy group)). In addition, onset of cardiovascular events and levels of markers that are associated with cardiovascular events are observed over time to examine the significance of each marker. The biomarkers will be obtained at the start of the study (at registration), after 6, 12, 24 and 36 months from the start of the study.

Detailed Description
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Events are defined as follows; Cerebrovascular events: Stroke (cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, unknown type of stroke), transient ischemic attack Coronary events: Myocardial infarction, angina pectoris, asymptomatic myocardial ischemia Cardiac events: Myocardial infarction, angina pectoris, asymptomatic myocardial ischemia, heart failure Aortic/peripheral arterial events: Aortic aneurysm, aortic dissection, arteriosclerotic disease (aorta, carotid artery, renal artery, mesenteric artery, peripheral artery, etc.) Complications of diabetes: Diabetic nephropathy*, diabetic retinopathy*, diabetic neuropathy* Aggravation of renal function: Doubling of serum creatinine level, ESRD (initiation of dialysis, renal transplantation) *Newly occurred or aggravated The followings will be measured as biomarkers; urinary albumin creatinine rates (UACR), plasma brain natriuretic peptide (BNP), urinary 8-hydroxy-deoxy-guanosine (8-OHdG), serum adiponectin, serum high-molecular weight adiponectin, high sensitivity c-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR)

Official Title
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A Trial of Telmisartan Prevention of Cardiovascular Disease

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Non-ARB (standard therapy)
* Drug: ARB (Telmisartan)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet all of the criteria listed in [1] to [4] below and who have at least one cardiovascular risk listed in [1] to [5] below will be included in the study. Outpatients Age: ≥ 40 to < 80 Hypertension: Systolic blood pressure of ≥ 140 mmHg or diastolic blood pressure of ≥ 90 mmHg in the two latest measurements of casual blood pressure (in the sitting position) regardless of treated or untreated condition, or systolic blood pressure of < 140 mmHg and diastolic blood pressure of < 90 mmHg that require antihypertensive treatment. Assessment of hypertension: Blood pressure will be measured at least twice at an interval of 1 to 2 minutes. If the measured values obtained are substantially different, additional measurements will be performed and the average of two stable measurements will be used for assessment. Patients who have given consent to participate in the present study. Cardiovascular risks: Diabetes mellitus; Type 2 diabetes mellitus Kidney; Serum creatinine: 1.2 mg/dL - < 2.0 mg/dL for males, 1.0 mg/dL - < 2.0 mg/dL for females Proteinuria: qualitative value of ≥ +1 (quantitative value: proteinuria with the value of ≥ 0.3 g/g・Cr in casual urine when adjusted with urine creatinine) CKD stage 3 or higher (GFR < 60 mL/min/1.73 m2) Heart; Previous myocardial infarction noted more than 6 months before obtaining the informed consent Diagnosis of angina pectoris Diagnosis of heart failure (NYHA I or II class) Diagnosis of left ventricular hypertrophy (left ventricular posterior wall of ≥ 12 mm evidenced by echocardiography performed prior to obtaining the informed consent, or Sv1+Rv5 of ≥ 35 mm noted as ECG finding) Diagnosis of transient or persisting atrial fibrillation Brain; Previous cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage or transient cerebral ischemic attack noted more than 6 months before obtaining the informed consent Peripheral arterial diseases; Previous lower-limb bypass surgery or angioplasty performed more than 6 months before obtaining the informed consent Ankle-brachial pressure index of < 0.9 or intermittent claudication Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study. Type 1 diabetes mellitus Severe renal disorders (serum creatinine of ≥ 2.0 mg/dL) Myocardial infarction, percutaneous transluminal angioplasty and bypass surgery of coronary artery/ lower-limb blood vessel, cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage and transient cerebral ischemic attack noted within 6 months before initiation of the observation Diagnosis of heart failure (NYHA III or IV class ) Virulent hypertension and secondary hypertension Pregnant women Clinically relevant allergic symptoms or past history of hypersensitivity to drugs / significant adverse drug reactions Extremely poor bile secretion or serious liver disorders Treatment-required malignant tumors Patients who are judged by the physician in charge to be ineligible for the study for any other reasons

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Non-ARB group<br> | Drug: Non-ARB (standard therapy)<br>* Blood pressure lowering therapy except ARB<br>|
| Active Comparator: ARB group<br> | Drug: ARB (Telmisartan)<br>* Telmisartan 20-80 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effects of ARB therapy and that of standard therapy except ARB on the biomarker levels (UACR and BNP) |  | for three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of the two treatments on the incidence of events, and the relationship between the incidence of events and the biomarker levels (UACR, BNP, urine 8-hydroxy-2-deoxyguanosine, serum adiponectin, serum high-molecule adiponectin, eGFR) |  | for three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, Cerebrovascular disease, Coronary Artery Disease, Chronic Kidney Disease, Peripheral Artery Disease