Clinical trial NCT01075698: A Trial of Telmisartan Prevention of Cardiovascular Disease
Official title: A Trial of Telmisartan Prevention of Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Type 2 Diabetes
Cerebrovascular disease
Coronary Artery Disease
Chronic Kidney Disease
Peripheral Artery Disease
Lead sponsor: Kumamoto University
Sponsor class: OTHER
Collaborators: name: Japan Foundation for Aging and Health
First posted: 2010-02-25
Enrollment: 1228
Sex: ALL
Minimum age (years): 40
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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.

1. Outpatients
2. Age: ≥ 40 to \< 80
3. 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.
4. Patients who have given consent to participate in the present study.

Cardiovascular risks:

1. Diabetes mellitus; Type 2 diabetes mellitus
2. 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)
3. 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
4. Brain; Previous cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage or transient cerebral ischemic attack noted more than 6 months before obtaining the informed consent
5. 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.

1. Type 1 diabetes mellitus
2. Severe renal disorders (serum creatinine of ≥ 2.0 mg/dL)
3. 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
4. Diagnosis of heart failure (NYHA III or IV class )
5. Virulent hypertension and secondary hypertension
6. Pregnant women
7. Clinically relevant allergic symptoms or past history of hypersensitivity to drugs / significant adverse drug reactions
8. Extremely poor bile secretion or serious liver disorders
9. Treatment-required malignant tumors
10. Patients who are judged by the physician in charge to be ineligible for the study for any other reasons

Primary outcomes:
measure: The effects of ARB therapy and that of standard therapy except ARB on the biomarker levels (UACR and BNP)
timeFrame: for three years
Secondary outcomes:
measure: 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)
timeFrame: for three years
Other outcomes:
Locations:
city: Kumamoto
country: Japan
facility: Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital
Study officials:
affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
name: Hisao Ogawa, Prof., MD, PhD
role: STUDY_CHAIR
affiliation: Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University
name: Shokei Kim-Mitsuyama, Prof., MD, PhD
role: STUDY_DIRECTOR
affiliation: Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine
name: Koichi Node, Prof, MD, PhD
role: STUDY_DIRECTOR
affiliation: Health Care Center / Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
name: Hirofumi Soejima, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital
name: Osamu Yasuda, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ogawa H, Soejima H, Matsui K, Kim-Mitsuyama S, Yasuda O, Node K, Yamamuro M, Yamamoto E, Kataoka K, Jinnouchi H, Sekigami T; ATTEMPT-CVD investigators. A trial of telmisartan prevention of cardiovascular diseases (ATTEMPT-CVD): Biomarker study. Eur J Prev Cardiol. 2016 Jun;23(9):913-21. doi: 10.1177/2047487315603221. Epub 2015 Aug 31.
citation: Kim-Mitsuyama S, Soejima H, Yasuda O, Node K, Jinnouchi H, Yamamoto E, Sekigami T, Ogawa H, Matsui K. Reduction in hsCRP levels is associated with decreased incidence of cardiovascular events in Japanese hypertensive women but not in men. Sci Rep. 2020 Oct 12;10(1):17040. doi: 10.1038/s41598-020-73905-4.