A Trial of Telmisartan Prevention of Cardiovascular Disease (ATTEMPT-CVD)

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Non-ARB (standard therapy); Drug: ARB (Telmisartan)

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)

• Study Type: Interventional
• Enrollment (Actual): 1228
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kumamoto, Japan, 860-8555
    • Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Kumamoto University
• Collaborators: Japan Foundation for Aging and Health
• Investigators: Study Chair: Hisao Ogawa, Prof., MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University; Study Director: Shokei Kim-Mitsuyama, Prof., MD, PhD, Department of Pharmacology and Molecular Therapeutics, Graduate School of Medical Sciences, Kumamoto University; Study Director: Koichi Node, Prof, MD, PhD, Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine; Principal Investigator: Hirofumi Soejima, MD, PhD, Health Care Center / Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University; Principal Investigator: Osamu Yasuda, MD, PhD, Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: February 24, 2010
• First Submitted That Met QC Criteria: February 24, 2010
• First Posted (Estimate): February 25, 2010

Study Record Updates

• Last Update Posted (Estimate): September 7, 2016
• Last Update Submitted That Met QC Criteria: September 3, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Chronic Kidney Disease; Type 2 Diabetes; Peripheral Artery Disease; Cerebrovascular disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Telmisartan
• Other Study ID Numbers: H21-1

Plan for Individual participant data (IPD)

Study Data/Documents

1. Study Protocol