A Study to Evaluate the Effects of Azilsartan on Coronary Artery Plaque in Essential Hypertensive Patients With Stable Angina and Dyslipidemia. (ALIVE)

The purpose of this study is to evaluate the effects of oral azilsartan once daily for 32 weeks on coronary artery plaque in essential hypertensive patients with stable angina and dyslipidemia.

Study Overview

• Status: Withdrawn
• Conditions: Essential Hypertension With Stable Angina and Dyslipidemia
• Intervention / Treatment: Drug: Azilsartan

Detailed Description

The open-label design without a control group was selected because this clinical study primarily aims to explore the effects of azilsartan on coronary artery plaques.

This study targeting patients with coronary artery plaque has been designed to enroll hypertensive patients with dyslipidemia. Also in light of the invasive nature of the major assessment procedures (i.e., IB-IVUS, OCT), this study will only enroll patients with stable angina planned to undergo percutaneous coronary intervention with stent placement, among patients with coronary artery plaque.

The starting dose of azilsartan has been set to 20 mg on the basis of the usual clinical dose of the drug in patients with essential hypertension, and dose increase of azilsartan will be permitted only when the target blood pressure has not been achieved.

The duration of treatment has been set to 32 weeks in line with clinical practice, in which coronary angiography is typically performed after a 32-week follow-up period following PCI with stent placement.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tokushima, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with essential hypertension with office blood pressure before the start of study treatment (Week 0) meeting the following criteria who are appropriate for azilsartan therapy in the opinion of the principal investigator or investigator

   • Patients aged ≥ 75 years at the time of informed consent: Sitting systolic blood pressure ≥ 150 mmHg or sitting diastolic blood pressure ≥ 90 mmHg
   • Patients aged < 75 years at the time of informed consent who concurrently have type 2 diabetes mellitus: Sitting systolic blood pressure ≥ 130 mmHg or sitting diastolic blood pressure ≥ 80 mmHg
   • Patients aged < 75 years at the time of informed consent who concurrently have chronic kidney disease (CKD) with proteinuria: Sitting systolic blood pressure ≥ 130 mmHg or sitting diastolic blood pressure ≥ 80 mmHg
   • Patients meeting none of the above: Sitting systolic blood pressure ≥ 140 mmHg or sitting diastolic blood pressure ≥ 90 mmHg
2. Patients with stable angina with a coronary stenosis confirmed by coronary angiography who are planned to undergo percutaneous coronary intervention with stent placement (any type of stent)
3. Patients with findings of integrated backscatter intravascular ultrasound (IB-IVUS) to be performed before the start of study treatment (Week 0) showing plaque at (≥ 5 mm in length) ≥ 5 mm proximal to the proximal end of the inserted stent in the coronary artery

4. Patients with dyslipidemia meeting both of the following criteria:

   • Patients treated with one HMG-CoA reductase inhibitor with no change in the dosage for at least 12 weeks before informed consent
   • Patients with an LDL-C level of < 100 mg/dL as shown by a laboratory test performed within 4 weeks before informed consent
5. Men or women aged 20 or older at the time of informed consent
6. Patients capable of making outpatient study visits throughout the observation period
7. Patients who, in the opinion of the principal investigator or investigator, are capable of understanding the contents of the clinical study and complying with the study requirements
8. Patients capable of providing written consent in person before any study procedures

Exclusion Criteria:

1. Patients with secondary hypertension or malignant hypertension
2. Patients who took any renin-angiotensin system inhibitor within 12 weeks before informed consent
3. Patients who previously underwent coronary artery bypass grafting
4. Patients with type 1 diabetes mellitus
5. Patients with insulin therapy
6. Patients with an HbA1c level (National Glycohemoglobin Standardization Program [NGSP] value) of ≥ 7.0% as shown by a laboratory test performed within 4 weeks before informed consent
7. Patients with the plaque unevaluable because of severe calcification of the coronary artery shown by IB-IVUS to be performed before the start of study treatment (Week 0)
8. Patients with a change to their antidyslipidemic medication (including a change to the dosage) within 12 weeks before informed consent
9. Patients with clinically evident renal disorder (defined as estimated glomerular filtration rate < 30 mL/min/1.73m2)
10. Patients with severe liver disorder
11. Patients with hyperkalemia (defined as serum potassium ≥ 5.5 mEq/L)
12. Patients with a history of hypersensitivity or allergy to azilsartan
13. Patients participating in any other clinical study
14. Pregnant women, women with possible pregnancy, or breastfeeding women
15. Other patients who are inappropriate for participation in this study in the opinion of the principal investigator or investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azilsartan; Azilsartan orally once daily in the morning, either before or after breakfast	Drug: Azilsartan; Azilsartan tablets; Other Names: Azilva tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in percentage of the lipid pool in the coronary artery plaque	Change in percentage of the lipid pool in the coronary artery plaque from the start of the treatment period at the end of the treatment period (Week 32). Percentage of the lipid pool in the coronary artery plaque is measured by integrated backscatter intravascular ultrasound (IB-IVUS).	32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in volume of the coronary artery plaque	Change in the volume of the coronary artery plaque from the start of the treatment period to the end of the treatment period. Change from baseline in volume of the coronary artery plaque is measured by integrated backscatter intravascular ultrasound (IB-IVUS).	32 weeks
Change in percentage of the fibrotic component in the coronary artery plaque	Change in percentage of the fibrotic component in the coronary artery plaque from the start of the treatment period at the end of the treatment period (Week 32). Percentage of the fibrotic component in the coronary artery plaque is measured by integrated backscatter intravascular ultrasound (IB-IVUS).	32 weeks
Change in percentage of the calcified component in the coronary artery plaque	Change in percentage of the calcified component in the coronary artery plaque from the start of the treatment period at the end of the treatment period (Week 32). Percentage of the calcified component in the coronary artery plaque is measured by integrated backscatter intravascular ultrasound (IB-IVUS).	32 weeks
Change in number of microchannels	Change from baseline in number of microchannels is measured by Optical Coherence Tomography(OCT).	32 weeks
Change in thickness of the fibrous cap	Change from baseline in number of microchannels is measured by Optical Coherence Tomography(OCT).	32 weeks

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: March 10, 2015
• First Submitted That Met QC Criteria: March 26, 2015
• First Posted (Estimate): March 27, 2015

Study Record Updates

• Last Update Posted (Estimate): May 24, 2016
• Last Update Submitted That Met QC Criteria: May 23, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacotherapy
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Pain; Neurologic Manifestations; Lipid Metabolism Disorders; Hypertension; Chest Pain; Dyslipidemias; Essential Hypertension; Angina Pectoris; Angina, Stable; Molecular Mechanisms of Pharmacological Action; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Azilsartan medoxomil
• Other Study ID Numbers: Azilsartan-4001; U1111-1167-9135 (Registry Identifier: WHO); JapicCTI-152834 (Registry Identifier: JapicCTI)