Essential HypertensionPhase 3NCT00818883
Efficacy and Safety of Azilsartan Medoxomil and Chlorthalidone in Participants With Moderate to Severe Hypertension
A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Azilsartan medoxomil and hydrochlorothiazide in people with Essential Hypertension, run by Takeda at 53 sites in 2 countries.
Trial summary
The purpose of this study is to compare the antihypertensive effect of chlorthalidone vs hydrochlorothiazide when each is used with azilsartan medoxomil, once daily (QD), in participants with moderate to severe essential hypertension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Essential Hypertension
- What is being tested?
- Azilsartan medoxomil and chlorthalidone and Azilsartan medoxomil and hydrochlorothiazide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 609 participants
- Where
- 53 sitesin 2 countries
- Study dates
- Feb 2009to Nov 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Is treated with antihypertensive therapy and has a post-washout mean sitting clinic SBP greater than or equal to 160 and less than or equal to 190 mm Hg on Day -1; or the participant has not received antihypertensive treatment within 28 days prior to Screening and has a mean sitting clinic SBP greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day -1.
- Females of childbearing potential who are sexually active agree to routinely use adequate contraception from Screening through 30 days after the last administered study drug dose.
- Has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
- Is willing to discontinue current antihypertensive medications on Day -21 or Day -28 if the participant is on amlodipine or chlorthalidone.
Who cannot join
- Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on Day -1.
- Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient quality.
- Works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]).
- Has an upper arm circumference less than 24 cm or greater than 42 cm.
- Is noncompliant (less than 70% or greater than 130%) with study medication during the placebo run-in period.
- Has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing's syndrome).
Show all 20Show fewer
- Has a recent history (within the last 6 months) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
- Has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome, atrial fibrillation, or atrial flutter).
- Has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
- Has severe renal dysfunction or disease [based on estimated glomerular filtration rate less than 30 mL/min/1.73m2 at Screening].
- Has known or suspected unilateral or bilateral renal artery stenosis.
- Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not apply to those participants with basal cell or stage I squamous cell carcinoma of the skin).
- Has poorly-controlled type 1 or type 2 diabetes mellitus at Screening.
- Has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory).
- Has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice.
- Has any other known serious disease or condition that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the participant according to the protocol.
- Has known hypersensitivity to angiotensin II receptor blockers or thiazide-type diuretics or other sulfonamide-derived compounds.
- Has been randomized in a previous azilsartan medoxomil study.
- Currently participating in another investigational study or is receiving or has received any investigational compound within 30 days prior to Screening.
- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
Trial locations and contacts
53 sites in 2 countries.
53 sites in 2 countries
United States50 sites
Study site
Adventura, Florida
Study site
Ann Arbor, Michigan
Study site
Asheboro, North Carolina
Study site
Atlanta, Georgia
Study site
Aventura, Florida
Study site
Birmingham, Alabama
Study site
Bloomington, Indiana
Study site
Brooksville, Florida
Study site
Bryan, Texas
Study site
Cincinnati, Ohio
Study site
City of Saint Peters, Missouri
Study site
Colorado Springs, Colorado
Study site
Crestview Hills, Kentucky
Study site
Crystal River, Florida
Study site
DeLand, Florida
Study site
Doral, Florida
Study site
Downingtown, Pennsylvania
Study site
Ettrick, Virginia
Study site
Gilbert, Arizona
Study site
Goose Creek, South Carolina
Study site
Gulf Shores, Alabama
Study site
Huntsville, Illinois
Study site
Kettering, Ohio
Study site
Lancaster, Pennsylvania
Study site
Lansdale, Pennsylvania
Study site
Lexington, Kentucky
Study site
Madison, Wisconsin
Study site
Miami, Florida
Study site
Milford, Connecticut
Study site
Naranja, Florida
Study site
New Windsor, New York
Study site
Paramount, California
Study site
Pittsburgh, Pennsylvania
Study site
Sacramento, California
Study site
San Antonio, Texas
Study site
San Diego, California
Study site
Sarasota, Florida
Study site
Scottsboro, Alabama
Study site
Seattle, Washington
Study site
Sierra Vista, Arizona
Study site
St Louis, Missouri
Study site
Stockbridge, Georgia
Study site
Suwanee, Georgia
Study site
Tampa, Florida
Study site
Taylors, South Carolina
Study site
Valparaiso, Indiana
Study site
West Palm Beach, Florida
Study site
West Yarmouth, Massachusetts
Study site
Wheat Ridge, Colorado
Study site
Winter Haven, Florida
About this study
Official title: A Phase 3, Double-Blind, Randomized, Efficacy and Safety Study of the TAK 491 Plus Chlorthalidone Fixed-Dose Combination Compared With TAK-491 and Hydrochlorothiazide Coadministration Therapy in Subjects With Moderate to Severe Essential Hypertension
The purpose of this study is to compare the antihypertensive effect of chlorthalidone vs hydrochlorothiazide when each is used with azilsartan medoxomil, once daily (QD), in participants with moderate to severe essential hypertension.
Read the detailed description
According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease, and renal failure. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one-third of patients continue to maintain control successfully.
Although most antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of antihypertensive agents. TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker being evaluated by Takeda to treat essential hypertension.
Treatments for essential hypertension commonly include use of a thiazide-like diuretic, either alone or as part of combination treatment. Although chlorthalidone was commonly prescribed in the past, its use has widely been replaced with hydrochlorothiazide, presumably due to a lack of available combination products containing chlorthalidone, the assumption that hydrochlorothiazide and chlorthalidone have similar antihypertensive effects and cardiovascular benefits, and the perception that chlorthalidone use is associated with a greater frequency of hypokalemia. However, the frequency of hypokalemia with chlorthalidone use is relatively low in the dose range of 12.5 to 25 mg and these doses have been shown to be associated with potent blood pressure reduction. Several long-term outcomes trials have shown that blood pressure reductions associated with chlorthalidone treatment reduce risk of cardiovascular morbidity and mortality.
Most hypertensive patients require two or more agents to achieve target blood pressure and diuretics are commonly used in combination with other antihypertensive agents. This trial is designed to compare chlorthalidone and hydrochlorothiazide when coadministered with azilsartan medoxomil.
Participants in this study will receive either chlorthalidone or hydrochlorothiazide in combination with azilsartan medoxomil. Total commitment time for this study is about 13 weeks. Participants will be required to wear a blood pressure monitor for three 24 hours periods during the study.
- Conditions
- Essential Hypertension
- Being tested
- Azilsartan medoxomil and chlorthalidone, Azilsartan medoxomil and hydrochlorothiazide
- Keywords
- Essential Hypertension, Hypertensive, Blood Pressure, High, Vascular Disease, Cardiovascular Disease, Drug Therapy
- Medical subject headings
- Essential Hypertension, Hypertension, Vascular Diseases, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Azilsartan medoxomil and chlorthalidoneDrug
Also called TAK-491, TAK-491CLD
Azilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 10 weeks.
For participants who do not achieve target blood pressure by Week 6, the dose of chlorthalidone will be increased for the remaining 4 weeks of treatment.
Azilsartan medoxomil and hydrochlorothiazideDrug
Also called TAK-491, TAK-491CLD
Azilsartan medoxomil 40 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 10 weeks.
For participants who do not achieve target blood pressure by Week 6, the dose of hydrochlorothiazide will be increased for the remaining 4 weeks of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Azilsartan Medoxomil 40 mg/Chlorthalidone 12.5 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan Medoxomil 40 mg + Hydrochlorothiazide 12.5 mg QD | Experimental | Not described Receives: Drug: Azilsartan medoxomil and hydrochlorothiazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure
The change in sitting trough clinic systolic blood pressure measured at each week indicated including final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Measured: Baseline, Week 6 and Week 10.
Secondary outcomes (14)
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure
The change in sitting trough clinic diastolic blood pressure measured at each week indicated including final visit relative to baseline. Diastolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in Mean Trough Systolic Blood Pressure (22 to 24 Hours After Dosing) as Measured by Ambulatory Blood Pressure Monitoring.
The change in trough systolic blood pressure measured at each week indicated including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing) as Measured by Ambulatory Blood Pressure Monitoring.
The change in trough diastolic blood pressure measured at each week indicated including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The trough is the average of all measurements recorded from 22 to 24 hours after dosing.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
The change in 24-hour mean systolic blood pressure measured at each visit indicated including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in 24-hour Mean Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
The change in 24-hour mean diastolic blood pressure measured at each visit indicated including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 24-hour mean is the average of all measurements recorded for 24 hours after dosing.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) mean systolic blood pressure measured at each visit including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
The change in daytime (6am to 10pm) mean diastolic blood pressure measured at each visit including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Daytime mean is the average of all measurements recorded between the hours of 6 am and 10 pm.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
The change in nighttime (12am to 6am) mean systolic blood pressure measured at each visit indicated including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
The change in nighttime (12am to 6am) mean diastolic blood pressure measured at each visit indicated including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. Nighttime mean is the average of all measurements recorded between the hours of 12 am and 6 am.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing as Measured by Ambulatory Blood Pressure Monitoring
The change in the 12-hour mean systolic blood pressure measured at each visit including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
Measured: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing as Measured by Ambulatory Blood Pressure Monitoring.
The change in the 12-hour mean diastolic blood pressure measured at each visit including final visit relative to baseline. Ambulatory blood pressure monitoring measures blood pressure at regular intervals throughout the day and night. The 12-hour mean is the average of all measurements recorded in the first 12 hours after dosing.
Measured: Baseline, Week 6 and Week 10.
Percentage of Participants Who Reached Their Trough, Sitting, Clinic Systolic Blood Pressure Targets, Defined as <140 mm Hg for Participants Without Diabetes or Chronic Kidney Disease or <130 mm Hg for Participants With Diabetes or Chronic Kidney Disease
Percentage of participants who achieve a clinic systolic blood pressure response measured at each week indicated, defined as <140mm Hg without diabetes or chronic kidney disease or <130/mm Hg with diabetes or chronic kidney disease. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
Measured: Week 2, Week 4, Week 6, Week 8 and Week 10.
Percentage of Participants Who Reached Their Trough, Sitting, Clinic Diastolic Blood Pressure Target, Defined as <90 mm Hg for Participants Without Diabetes or Chronic Kidney Disease or <80 mm Hg for Participants With Diabetes or Chronic Kidney Disease.
Percentage of participants who achieve a clinic diastolic blood pressure response measured at each week indicated, defined as <90 mm Hg for participants without diabetes or chronic kidney disease or <80 mm Hg for participants with diabetes or chronic kidney disease. Diastolic blood pressure is the average of the 3 serial trough sitting diastolic blood pressure measurements.
Measured: Week 2, Week 4, Week 6, Week 8 and Week 10.
Percentage of Participants Who Reached Their Trough, Sitting, Clinic Systolic and Diastolic Blood Pressure Targets, Defined as <140/90 mm Hg Without Diabetes or Chronic Kidney Disease or <130/80 mm Hg With Diabetes or Chronic Kidney Disease
Percentage of participants who achieve both a clinic systolic and diastolic blood pressure response measured at each week indicated, defined as <140/90 mm Hg for participants without diabetes or chronic kidney disease or <130/80 mm Hg for participants with diabetes or chronic kidney disease[GFR <60 mL/min/1.73 m2 or urinary albumin:creatinine ratio (UACR) >200 mg albumin/g creatinine at Screening.] Systolic/diastolic blood pressure is the average of the 3 serial trough sitting systolic/diastolic blood pressure measurements.
Measured: Week 2, Week 4, Week 6, Week 8 and Week 10.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2009 (estimated)
- Study startFeb 2009
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Essential HypertensionStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 609 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Executive Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00818883
- Sponsor's protocol ID
- TAK-491CLD_306
- Other IDs
- U1111-1112-7119
- Status last verified
- Jan 2012
- First submitted
- 7 Jan 2009
- Last updated
- 7 Feb 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bakris GL, Sica D, White WB, Cushman WC, Weber MA, Handley A, Song E, Kupfer S. Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. Am J Med. 2012 Dec;125(12):1229.e1-1229.e10. doi: 10.1016/j.amjmed.2012.05.023. Epub 2012 Aug 30.
PubMed 22939358
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Randomized, Efficacy and Safety Study of the TAK 491 Plus Chlorthalidone Fixed-Dose Combination Compared With TAK-491 and Hydrochlorothiazide Coadministration Therapy in Subjects With Moderate to Severe Essential Hypertension
- ClinicalTrials.gov ID
- NCT00818883
- Acronym / sponsor ID
- TAK-491CLD_306
- Conditions
- Essential Hypertension
- Keywords
- Essential Hypertension, Hypertensive, Blood Pressure, High, Vascular Disease, Cardiovascular Disease, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 609 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Feb 2009
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 8 Jan 2009 (estimated)
- Results
- Posted 7 Feb 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the antihypertensive effect of chlorthalidone vs hydrochlorothiazide when each is used with azilsartan medoxomil, once daily (QD), in participants with moderate to severe essential hypertension.
Detailed description
According to the World Health Organization, hypertension is the most common attributable cause of preventable death in developed nations, as uncontrolled hypertension greatly increases the risk of cardiovascular disease, cerebrovascular disease, and renal failure. Despite the availability of antihypertensive agents, hypertension remains inadequately controlled; only about one-third of patients continue to maintain control successfully.
Although most antihypertensive agents are effective at the appropriate dose, the majority have side effects that limit their use. As a class, angiotensin II receptor blockers generally are considered more tolerable than other classes of antihypertensive agents. TAK-491 (azilsartan medoxomil) is an angiotensin II receptor blocker being evaluated by Takeda to treat essential hypertension.
Treatments for essential hypertension commonly include use of a thiazide-like diuretic, either alone or as part of combination treatment. Although chlorthalidone was commonly prescribed in the past, its use has widely been replaced with hydrochlorothiazide, presumably due to a lack of available combination products containing chlorthalidone, the assumption that hydrochlorothiazide and chlorthalidone have similar antihypertensive effects and cardiovascular benefits, and the perception that chlorthalidone use is associated with a greater frequency of hypokalemia. However, the frequency of hypokalemia with chlorthalidone use is relatively low in the dose range of 12.5 to 25 mg and these doses have been shown to be associated with potent blood pressure reduction. Several long-term outcomes trials have shown that blood pressure reductions associated with chlorthalidone treatment reduce risk of cardiovascular morbidity and mortality.
Most hypertensive patients require two or more agents to achieve target blood pressure and diuretics are commonly used in combination with other antihypertensive agents. This trial is designed to compare chlorthalidone and hydrochlorothiazide when coadministered with azilsartan medoxomil.
Participants in this study will receive either chlorthalidone or hydrochlorothiazide in combination with azilsartan medoxomil. Total commitment time for this study is about 13 weeks. Participants will be required to wear a blood pressure monitor for three 24 hours periods during the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azilsartan Medoxomil 40 mg/Chlorthalidone 12.5 mg QD | Experimental | Drug: Azilsartan medoxomil and chlorthalidone |
| Azilsartan Medoxomil 40 mg + Hydrochlorothiazide 12.5 mg QD | Experimental | Drug: Azilsartan medoxomil and hydrochlorothiazide |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Is treated with antihypertensive therapy and has a post-washout mean sitting clinic SBP greater than or equal to 160 and less than or equal to 190 mm Hg on Day -1; or the participant has not received antihypertensive treatment within 28 days prior to Screening and has a mean sitting clinic SBP greater than or equal to 160 and less than or equal to 190 mm Hg at the Screening Visit and on Day -1.
- Females of childbearing potential who are sexually active agree to routinely use adequate contraception from Screening through 30 days after the last administered study drug dose.
- Has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant.
- Is willing to discontinue current antihypertensive medications on Day -21 or Day -28 if the participant is on amlodipine or chlorthalidone.
Key exclusion criteria (20 listed)
- Has a mean sitting clinic diastolic blood pressure greater than 119 mm Hg on Day -1.
- Has a baseline 24-hour ambulatory blood pressure monitoring reading of insufficient quality.
- Works a night (third) shift (defined as 11 PM [2300] to 7 AM [0700]).
- Has an upper arm circumference less than 24 cm or greater than 42 cm.
- Is noncompliant (less than 70% or greater than 130%) with study medication during the placebo run-in period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Azilsartan medoxomil and chlorthalidoneAlso: TAK-491, TAK-491CLDAzilsartan medoxomil 40 mg and chlorthalidone 12.5 mg combination tablet, orally, once daily and hydrochlorothiazide placebo-matching tablets, orally, once daily for up to 10 weeks. For participants who do not achieve target blood pressure by Week 6, the dose of chlorthalidone will be increased for the remaining 4 weeks of treatment. | Drug | Azilsartan Medoxomil 40 mg/Chlorthalidone 12.5 mg QD |
| Azilsartan medoxomil and hydrochlorothiazideAlso: TAK-491, TAK-491CLDAzilsartan medoxomil 40 mg, tablets, orally, once daily and hydrochlorothiazide 12.5 mg, tablets, orally, once daily for up to 10 weeks. For participants who do not achieve target blood pressure by Week 6, the dose of hydrochlorothiazide will be increased for the remaining 4 weeks of treatment. | Drug | Azilsartan Medoxomil 40 mg + Hydrochlorothiazide 12.5 mg QD |
Primary outcome
Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure
Time frame: Baseline, Week 6 and Week 10.
The change in sitting trough clinic systolic blood pressure measured at each week indicated including final visit relative to baseline. Systolic blood pressure is the average of the 3 serial trough sitting systolic blood pressure measurements.
14 secondary outcomes
Change From Baseline in Trough, Sitting, Clinic Diastolic Blood Pressure
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in Mean Trough Systolic Blood Pressure (22 to 24 Hours After Dosing) as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in Mean Trough Diastolic Blood Pressure (22 to 24 Hours After Dosing) as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in 24-hour Mean Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in 24-hour Mean Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Systolic Blood Pressure at 0 to 12 Hours After Dosing as Measured by Ambulatory Blood Pressure Monitoring
Time frame: Baseline, Week 6 and Week 10.
Change From Baseline in the Mean Diastolic Blood Pressure at 0 to 12 Hours After Dosing as Measured by Ambulatory Blood Pressure Monitoring.
Time frame: Baseline, Week 6 and Week 10.
Percentage of Participants Who Reached Their Trough, Sitting, Clinic Systolic Blood Pressure Targets, Defined as <140 mm Hg for Participants Without Diabetes or Chronic Kidney Disease or <130 mm Hg for Participants With Diabetes or Chronic Kidney Disease
Time frame: Week 2, Week 4, Week 6, Week 8 and Week 10.
Percentage of Participants Who Reached Their Trough, Sitting, Clinic Diastolic Blood Pressure Target, Defined as <90 mm Hg for Participants Without Diabetes or Chronic Kidney Disease or <80 mm Hg for Participants With Diabetes or Chronic Kidney Disease.
Time frame: Week 2, Week 4, Week 6, Week 8 and Week 10.
Percentage of Participants Who Reached Their Trough, Sitting, Clinic Systolic and Diastolic Blood Pressure Targets, Defined as <140/90 mm Hg Without Diabetes or Chronic Kidney Disease or <130/80 mm Hg With Diabetes or Chronic Kidney Disease
Time frame: Week 2, Week 4, Week 6, Week 8 and Week 10.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22939358Bakris GL, Sica D, White WB, Cushman WC, Weber MA, Handley A, Song E, Kupfer S. Antihypertensive efficacy of hydrochlorothiazide vs chlorthalidone combined with azilsartan medoxomil. Am J Med. 2012 Dec;125(12):1229.e1-1229.e10. doi: 10.1016/j.amjmed.2012.05.023. Epub 2012 Aug 30.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Executive Medical Director study director
Takeda
53 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Azilsartan medoxomil and chlorthalidone and Azilsartan medoxomil and hydrochlorothiazide in people with Essential Hypertension, run by Takeda at 53 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Feb 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Trough, Sitting, Clinic Systolic Blood Pressure (time frame: Baseline, Week 6 and Week 10.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00818883, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2012.