Azilsartan Circadian and Sleep Pressure

Azilsartan Circadian and Sleep Pressure - the 1st Study

To determine the efficacy of Azilsartan 20 mg versus Amlodipine 5 mg oral administration once per day for 8 weeks in patients with grade I or grade II essential hypertension.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Azilsartan; Drug: Amlodipine

Detailed Description

Treatment

<Run-in period> Use of any antihypertensives, including azilsartan and amlodipine, is prohibited during the run-in period.

<Treatment period> Subjects who are considered eligible for participation in the study based on the results of eligibility assessment during the run-in period will be randomized to the azilsartan 20 mg or amlodipine 5 mg group at a ratio of 1:1 according to the following stratification factors; the type of awake-sleep blood pressure variation determined based on the data from ABPM at the start of run-in, complication status (chronic kidney diseases [CKD], type 2 diabetes), age, and sex.

Subjects will start treatment with either antihypertensive after examination for the start of treatment (Week 0) and visit the study site every 2 weeks, 5 visits in total, until the end of treatment (Week 8).

Subjects will orally take azilsartan 20 mg or amlodipine 5 mg, according to their group allocation, once daily before or after breakfast in the morning.

• Study Type: Interventional
• Enrollment (Actual): 957
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Hakataeki-higashi Clinic
  • Fukuoka, Japan
    • Ogata Medical Clinic
  • Fukuoka, Japan
    • Soejima Naika Clinic
  • Hiroshima, Japan
    • Inoue Neurology Clinic
  • Hiroshima, Japan
    • Oda medical Clinic
  • Hukuoka, Japan
    • Aiseikai PS Clinic
  • Nagasaki, Japan
    • Kosei-kai Nijigaoka Hospital
  • Okayama, Japan
    • Seizenkai Okayama Saidaiji Hospital
  • Okayama, Japan
    • Yasuda Clinic
  • Osaka, Japan
    • AMC Nishiumeda Clinic
  • Osaka, Japan
    • Kouseikai Chimori Medical Clinic
  • Saitama, Japan
    • H&Y Akimoto Naika Clinic
  • Saitama, Japan
    • Shiseidou Tomita Hospital
  • Saitama, Japan
    • Takahashi Clinic
  • Aichi
    • Niihama, Aichi, Japan
      • Jyuzen General Hospital
    • Tsushima, Aichi, Japan
      • Junn Clinic
  • Chiba
    • Matsudo, Chiba, Japan
      • Seikei-kai New Tokyo Hospital
  • Fukuoka
    • Chikushino, Fukuoka, Japan
      • Sanshukai Doi Internal Medicine Clinic
    • Itoshima, Fukuoka, Japan
      • Junshinkai Nakamura Cardiovascular Clinic
    • Kitakyusyu, Fukuoka, Japan
      • Osaki Clinic
    • Kitakyusyu, Fukuoka, Japan
      • Osamura Medical Clinic
  • Fukushima
    • Koriyama, Fukushima, Japan
      • Hoshi general hospital
  • Gunma
    • Maebashi, Gunma, Japan
      • Zensyukai Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan
      • Hakushoukai Sano Hospital
    • Asahikawa, Hokkaido, Japan
      • Jiseikai Higashiasahikawa Hospital
    • Asahikawa, Hokkaido, Japan
      • Koushinkai Shintomi Naika Clinic
    • Sapporo, Hokkaido, Japan
      • Aoki Clinic
    • Sapporo, Hokkaido, Japan
      • Houwakai Sapporo Hospital
    • Sapporo, Hokkaido, Japan
      • Mitani Clinic
    • Sapporo, Hokkaido, Japan
      • Shinkotoni Family Clinic
    • Sapporo, Hokkaido, Japan
      • Shoureikan Shinsapporo Seiryou Hospital
    • Tomakomai, Hokkaido, Japan
      • Tomakomai City Hospital
  • Hukuoka
    • Itoshima, Hukuoka, Japan
      • Hukuyo naika clinic
    • Kitakyushu, Hukuoka, Japan
      • Asunaro medical Clinic
  • Hyogo
    • Amagasaki, Hyogo, Japan
      • Keiseikai Gohshi Hospital
  • Ibaraki
    • Koga, Ibaraki, Japan
      • Keijukai Itabashi Clinic
  • Iwate
    • Morioka, Iwate, Japan
      • Kamata medical Clinic
  • Kagoshima
    • Ichikikushikino, Kagoshima, Japan
      • Koyokai Hanamure Hospital
    • Izumi, Kagoshima, Japan
      • Izumi General Medical Center
  • Kanagawa
    • Kamakura, Kanagawa, Japan
      • Iroden Clinic
    • Kamakura, Kanagawa, Japan
      • Nagasu Clinic
    • Kawasaki, Kanagawa, Japan
      • Himawari-kai Kanagawa Himawari Clinic
    • Kawasaki, Kanagawa, Japan
      • Kawasaki Saiwai Clinic
    • Kawasaki, Kanagawa, Japan
      • Wakoukai Kawasaki Rinko General Hospital
    • Sagamihara, Kanagawa, Japan
      • Yamamoto Clinic
    • Sagamihara, Kanagawa, Japan
      • Hakuai Clinic
    • Sagamihara, Kanagawa, Japan
      • Kaneshiro Diabetes Clinic
    • Yamato, Kanagawa, Japan
      • Tsuruma Kaneshiro Diabetes Clinic
    • Yokohama, Kanagawa, Japan
      • Furuie Clinic
    • Yokohama, Kanagawa, Japan
      • Minamisawa Clinic
    • Yokohama, Kanagawa, Japan
      • Shintoukai Yokohama Minoru Clinic
    • Yokohama, Kanagawa, Japan
      • Shuyu-kai Kikuchi Clinic
    • Yokohama, Kanagawa, Japan
      • Tani Clinic
  • Miyagi
    • Sendai, Miyagi, Japan
      • HIGASHIKATSUYAMA nakazawa Naika allergy Internal Medicine
    • Sendai, Miyagi, Japan
      • Shinden Higashi Clinic
  • Nagasaki
    • Omura, Nagasaki, Japan
      • Meiwakai Izaki Clinic
  • Oita
    • Beppu, Oita, Japan
      • Shoninkai Shonin Hospital
  • Okayama
    • Tsuyama, Okayama, Japan
      • Hirano Doujinkai Tsuyama Daiichi Hospital
    • Wake-gun, Okayama, Japan
      • Taira Hospital
  • Osaka
    • Takatsuki, Osaka, Japan
      • Tenjin Tanaka Internal Medicine Clinic
  • Saitama
    • Ageo, Saitama, Japan
      • Enomoto Clinic
    • Kazo, Saitama, Japan
      • Kazo Minami Clinic
    • Kumagaya, Saitama, Japan
      • Asukurepiosu Enomoto Clinic
    • Kumagaya, Saitama, Japan
      • Shibuya Clinic
    • Tokorozawa, Saitama, Japan
      • Genkikai Wakasa Clinic
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan
      • JA Shizuoka Kohseiren Enshu Hospital
    • Shimoda, Shizuoka, Japan
      • Shimoda Medical Center
  • Tochigi
    • Shimotsuke, Tochigi, Japan
      • Jichi medical university hospital
    • Utsunomiya, Tochigi, Japan
      • DIC Utsunomiya Central Clinic
  • Tokyo
    • Arakawa-ku, Tokyo, Japan
      • Nippori Clinic
    • Chofu, Tokyo, Japan
      • Eireikai Niwa Family Clinic
    • Chuo-ku, Tokyo, Japan
      • Keiyu Clinic
    • Chuo-ku, Tokyo, Japan
      • Nihonbashikabutocho Nakajima Clinic
    • Chuo-ku, Tokyo, Japan
      • Tokyo Center Clinic
    • Edogawa-ku, Tokyo, Japan
      • Taiseikai Seikoudou Clinic
    • Koto-ku, Tokyo, Japan
      • Hirookai Kanbara Clinic
    • Koto-ku, Tokyo, Japan
      • Ono Medical Clinic
    • Koto-ku, Tokyo, Japan
      • Sawai Medical Clinic
    • Koto-ku, Tokyo, Japan
      • Shinsei-kai Kameido Ekimae Ckinic
    • Koto-ku, Tokyo, Japan
      • Shinseikai Kameido Minami-guchi Clinic
    • Mitaka, Tokyo, Japan
      • Kamada Clinic
    • Mitaka, Tokyo, Japan
      • Mitaka Health Care Clinic
    • Mitaka, Tokyo, Japan
      • Murenosato Clinic
    • Musashino, Tokyo, Japan
      • Shirayurikai Swing Bldg Nozaki Clinic
    • Ota-ku, Tokyo, Japan
      • Kenkoukan Suzuki Clinic
    • Setagaya-ku, Tokyo, Japan
      • Keichikai Shimokitazawa Tomo Clinic
    • Shinjuku-ku, Tokyo, Japan
      • Ishinkai Oda Clinic
    • Shinjuku-ku, Tokyo, Japan
      • Ryousyukai Kanauchi Medical Clinic
    • Suginami-ku, Tokyo, Japan
      • Shingakai MaO Clinic
    • Toshima-ku, Tokyo, Japan
      • Keiseikai Otsuka Kita-guchi Clinic
  • Yamaguchi
    • Ube, Yamaguchi, Japan
      • Fujino Clinic
  • Yamanashi
    • Tsuru, Yamanashi, Japan
      • Hirokai Higashikatsura Medical Clinic

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:

• Grade I or II essential hypertension
• The sitting systolic blood pressure is in term of 140-179 mmHg, or sitting diastolic blood pressure is in term of 90-109 mmHg at the both two time points at the beginning of the observation period and at the beginning of a treatment period (Week0)
• 20 years old or older at the time of the informed consent
• Able to give written informed consent before participating in the research
• Therapeutic category during the observation period: Ambulatory

Exclusion Criteria:

• Secondary hypertension, grade III hypertension (sitting systolic blood pressure greater than or equal to 180 mmHg or sitting diastolic blood pressure greater than or equal to 110 mmHg), malignant hypertension
• More than 2 kinds of antihypertensive agents for treatment on the hypertension
• History of taking following medicines within 2 weeks before start of the observation period.

When subject with taking any of the following medicine at the time of informed consent is included, stop to take the medicine for determined period after the informed consent.

I. Antihypertensive agents II. Antianginal agents III. Antiarrhythmic agents (except single time use of the lidocaine hydrochloride formulation for anesthesia) IV. Digitalis products

• Less than 130 mmHg of mean 24-hour systolic blood pressure and less than 80 mmHg of mean 24-hour diastolic blood pressure at the start of the observation period.
• History of following circulatory-related diseases or symptoms within 24 weeks before start of the observation period.

I. Cardiac disease: Myocardial infarction, coronary artery revascularization II. Cerebrovascular-disease: cerebral infarction, cerebral hemorrhage, transient ischemic attack III. Progressive hypertensive retinopathy: hemorrhage, exudation, or papilledema

• History or complication with the following circulatory-related diseases; Valvular stenosis, atrial fibrillation, pharmacotherapy-required angina, congestion heart failure, or cardiac arrhythmia, or arteriosclerosis obliterans with symptoms of intermittent claudication et al
• Day / night reversal
• History of hypersensitivity or allergy to Azilsartan, Amlodipine, or related drugs
• Participant in any other clinical research
• Pregnant, possible to being pregnant, or lactating woman
• Mal-control of blood pressure during informed consent to taking antihypertensive agent
• Any those the investigator or other researchers consider as unsuitable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Azilsartan; Azilsartan 20mg/day in oral administration, single dose Treatment duration: 8 weeks	Drug: Azilsartan; Azilsartan 20mg/day; Other Names: AZILVA Tablets
ACTIVE_COMPARATOR: Amlodipine; Amlodipine 5mg/day in oral administration, single dose Treatment duration: 8 weeks	Drug: Amlodipine; Amlodipine 5mg/day; Other Names: Amlodin Tablets etc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Nocturnal Systolic Blood Pressure Level	Change at the end of a treatment period (Week 8) from the beginning point of an observation period *Nocturnal systolic blood pressure level: the mean value of systolic arterial pressure during night (during sleeping)	Baseline and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Absolute Value in Difference With Targeted Value* (15 Percent) of Nocturnal Systolic Blood Pressure Fall**	Change from the start of the run-in period (Week -1) at the end of the treatment period (Week 8) *The targeted value has been set as the median of the dipping rate, normal type of nocturnal blood pressure variation, rate of nocturnal blood pressure fall (10-20 percent) ** Rate of nocturnal blood pressure fall: calculated as (awake SBP-sleep SBP)/awake SBP	Baseline and 8 weeks
Change in Nocturnal Diastolic Blood Pressure Level	Change from the start of the run-in period (Week -1) at the end of the treatment period (Week 8)	Baseline and 8 weeks
Change in 24-hour Mean Systolic Blood Pressure Level	Change from the start of the run-in period (Week -1) at the end of the treatment period (Week 8)	Baseline and 8 weeks
Change in 24-hour Mean Diastolic Blood Pressure Level	Change from the start of the run-in period (Week -1) at the end of the treatment period (Week 8)	Baseline and 8 weeks

Collaborators and Investigators

• Sponsor: Sogo Rinsho Médéfi Co., Ltd.
• Collaborators: Takeda
• Investigators: Principal Investigator: Kazuo Kario, Chief Professor of Division of Cardiovascular Medicine, Jichi Medical University

Publications and helpful links

General Publications

• Kario K, Hoshide S. Age-related difference in the sleep pressure-lowering effect between an angiotensin II receptor blocker and a calcium channel blocker in Asian hypertensives: the ACS1 Study. Hypertension. 2015 Apr;65(4):729-35. doi: 10.1161/HYPERTENSIONAHA.114.04935. Epub 2015 Feb 2.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): December 1, 2013
• Study Completion (ACTUAL): December 1, 2013

Study Registration Dates

• First Submitted: December 18, 2012
• First Submitted That Met QC Criteria: January 4, 2013
• First Posted (ESTIMATE): January 7, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 28, 2015
• Last Update Submitted That Met QC Criteria: November 19, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Amlodipine; Azilsartan medoxomil
• Other Study ID Numbers: ACS1