Effect of Azilsartan on Atrial Fibrillation in Patients With Hypertension (AZAF)

April 23, 2023 updated by: Beijing Tsinghua Chang Gung Hospital

Effect of Azilsartan on the Incidence of Atrial Fibrillation in Patients With Hypertension Combined With Left Ventricular Hypertrophy

Hypertension and atrial fibrillation (AF) are two major public health problems worldwide. Hypertension is an important risk factor for AF, and the combination of which could significantly increase the risk of cardiovascular adverse events, and result greater disability rate and mortality.

Hypertension can stimulate cardiomyocytes apoptosis, drive renin-angiotensin-aldosterone system (RAAS) activation, lead to left ventricular hypertrophy (LVH) and finally result in the structure remodeling of the atrium, which can trigger AF development through influence on myocardial electrical activity. Previous studies have found that angiotensin receptor blockers (ARB) seem to be more efficient in preventing AF when hypertension combined heart failure or LVH, but not completely clear in others with hypertension.

Azilsartan is a new ARB, it replaces the tetrazole ring of the traditional ARB with the oxadiazole ring, which making it binds to the angiotensin type 1 (AT1) receptor more tightly, dissociate more slowly, and has a stronger antihypertensive effect. It was reported that Azilsartan could inhibit cell proliferation, reduce inflammation and oxidative stress. However, whether Azilsartan can reduce the risk of AF in hypertensive patients, and the possible corresponding mechanism is still unclear.

Accordingly, the investigators designed this study intending to evaluate the effect of Azilsartan on the incidence of AF in hypertensive patients combined with LVH, and to explore the possible mechanism. This study is a practical, multicenter randomized controlled research method, the investigators will include 400 patients with hypertension and LVH who meet the inclusion criteria in Beijing Tsinghua Changgung Hospital and other centers. The patients would be divided into the Azilsartan group and conventional treatment group randomly, and be followed up regularly for 12 months. The incidence of AF in the two groups would be compared through the flexible intelligent ECG monitoring system, and the optimal blood pressure control, also the left ventricular hypertrophy and left atrial function would be evaluated.

This study will provide evidence for the use of Azilsartan in blood pressure control and lower risk for AF patients with hypertension and LVH. It will be benefit for improving prognosis of patients with hypertension combined LVH, reducing the incidence of AF, and achieving good social economic effects.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 102218
        • Beijing Tsinghua Chang Gung Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years.
  • Satisfied the diagnostic criteria for hypertension in the 2020 International Society of Hypertension Global Practice Guidelines for Hypertension.
  • Blood pressure control fails to meet one of the following conditions: office blood pressure ≥ 140/90mmHg; ambulatory blood pressure monitoring daytime average blood pressure ≥ 135/85mmHg or nighttime average blood pressure ≥ 120/70mmHg; home monitoring blood pressure ≥ 135/85mmHg.
  • Echocardiography shows that the left ventricular wall thickness is ≥11 mm, or the left ventricular mass index (LVMI) is >95 g/m2 (female), 115 g/m2 (male).

Exclusion Criteria:

  • Secondary hypertension.
  • Confirmed diagnosis of persistent atrial fibrillation.
  • Severe liver and kidney disease (eGFR<30 mL/min/1.73m2), severe lung disease, malignant tumor and mental illness history.
  • Pregnant women, women of childbearing age who plan to become pregnant during the study or who cannot use effective contraception during the study
  • Illness leading to life expectancy <12 months.
  • Not signed informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Azilsartan treatment group
In the Azilsartan group, Azilsartan will be added in or switched to the original antihypertensive treatment plan, starting as 20 mg Qd, and gradually increased to 40 mg Qd according to the blood pressure. If the blood pressure is still not be controlled, antihypertensive drugs other than ACEI, ARB or ARNI will be added until the blood pressure is controlled.
Drug: Azilsartan or antihypertensive drugs other than ACEI, ARB or ARNI
The patient's ECG information will be monitored through the ECG monitoring patch, and the time of the first atrial fibrillation event will be recorded. Monitoring whether the patient's blood pressure is controlled dynamically, using echocardiography to evaluate cardiac function, and using scales to assess the quality of life.
Active Comparator: Conventional treatment group
In the routine treatment group, antihypertensive treatment programs other than ACEI, ARB or ARNI will be adopted, and the use of antihypertensive drugs will be adjusted until the blood pressure control is controlled.
Drug: Azilsartan or antihypertensive drugs other than ACEI, ARB or ARNI
The patient's ECG information will be monitored through the ECG monitoring patch, and the time of the first atrial fibrillation event will be recorded. Monitoring whether the patient's blood pressure is controlled dynamically, using echocardiography to evaluate cardiac function, and using scales to assess the quality of life.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and burden of atrial fibrillation
Time Frame: The patient's ECG information will be recorded once a month, and be continuously monitored for 7 days at each time. A 24-hour Holter electrocardiogram was performed within 48 weeks.
In this study, atrial fibrillation includes both paroxysmal or persistent atrial fibrillation. Paroxysmal atrial fibrillation refers to that lasts for more than 30 seconds but less than 7 days, and the persistent one refers to that lasts over 7 days. Atrial fibrillation burden is defined as the percentage of analyzable wear time in AF.
The patient's ECG information will be recorded once a month, and be continuously monitored for 7 days at each time. A 24-hour Holter electrocardiogram was performed within 48 weeks.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Control of Blood pressure
Time Frame: Patients will conduct self-test blood pressure 3 days a week, once in the morning and once in the evening. A 12-week interval is used to calculate the TITRE values of the two groups of patients at 0-12 weeks, 13-24 weeks, 25-36 weeks, and 37-48 weeks.
In this study, the percentage time to achieve blood pressure target (TITRE) and ambulatory blood pressure monitoring will be used to evaluate the achievement of blood pressure target. Greater percentage time at target (TITRE) was associated with lower risk of incident cardiovascular diseases and was an effective predictor of clinical outcomes, with a high clinical relevance and actionability. The standard calculation method of TITRE is based on that reported in previous studies.
Patients will conduct self-test blood pressure 3 days a week, once in the morning and once in the evening. A 12-week interval is used to calculate the TITRE values of the two groups of patients at 0-12 weeks, 13-24 weeks, 25-36 weeks, and 37-48 weeks.
Evaluation of left ventricular hypertrophy and left atrial dimension
Time Frame: From baseline to the end of study.
Two-dimensional transthoracic echocardiography (2DE) diastolic interventricular septal thickness (IVST) or left ventricular posterior wall thickness (PWT) and left ventricular mass index (LVMI) will be used to evaluate left ventricular hypertrophy. According to the guidelines, IVST or PWT ≥ 11mm, LVMI > 95g/m2 (female)/115 g/m2 (male) is defined as left ventricular hypertrophy. Left atrial dimension is evaluated by left atrial volume index (LAVI). Left atrial volume is measured by two-dimensional echocardiography, and the left atrial volume index (LAVI) is obtained by correcting body surface area.
From baseline to the end of study.
Healthy quality of life
Time Frame: From baseline to end of study
In this study, three-level EuroQol five-dimensions (EQ-5D-3L) will be used to assess the patient's quality of life, and the difference in the change in the quality of life between the two groups will be compared. The EQ-5D-3L is a self-assessment scale which includes five dimensions: mobility, self-care, daily activities, pain or discomfort, and depression. There are three categories of options for each dimension (Normal, Moderately Restricted, Severely Restricted). This commonly used health utility measure converts quality of life and health status into quality-adjusted life years (QALYs).
From baseline to end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Tsinghua Chang Gung Hospital

Investigators

  • Study Chair: He Rong, M.D., Ph.D, Beijing Tsinghua Chang Gung Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

June 1, 2023

Primary Completion (Anticipated)

June 1, 2025

Study Completion (Anticipated)

October 1, 2025

Study Registration Dates

First Submitted

March 23, 2023

First Submitted That Met QC Criteria

April 23, 2023

First Posted (Actual)

May 3, 2023

Study Record Updates

Last Update Posted (Actual)

May 3, 2023

Last Update Submitted That Met QC Criteria

April 23, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-CCA-HX-009

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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