Clinical trial NCT00649389: Safety and Efficacy Study of a Triple Combination Therapy in Subjects With Hypertension
Official title: A Randomized, Double-Blind, Parallel Group Study Evaluating the Efficacy and Safety of Co-Administration of a Triple Combination Therapy of Olmesartan Medoxomil, Amlodipine Besylate and Hydrochlorothiazide in Subjects With Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2008-04-01
Enrollment: 2500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine the effectiveness of four different strength combinations of three approved anti-hypertension therapies (olmesartan medoxomil, amlodipine, and hydrochlorothiazide) for lowering blood pressure.


Eligibility criteria: Inclusion Criteria:

* Demonstrable hypertension defined as mean sitting trough cuff blood pressure ≥ 140/100 mmHg (SeSBP ≥ 140 mmHg and SeDBP ≥ 100mmHg) or mean sitting trough cuff BP ≥ 160/90 mmHg (SeSBP ≥ 160 mmHg and SeDBP ≥ 90mmHg).
* Male or female newly diagnosed hypertensive subjects or currently on hypertension medication.

  * Negative urine pregnancy test at screening
  * Not lactating
  * Do not plan to become pregnant during the study
  * Will practice birth control throughout the study by the following: oral or patch contraceptive, injectable or implantable contraceptive medication, intrauterine device, diaphragm or female condom plus spermicide

    * Non childbearing potential must be classified by one of the following criteria
    * Had a hysterectomy or tubal ligation at least 6 months prior to consent
    * Has been postmenopausal for a least 1 year

Exclusion Criteria:

* Mean sitting trough cuff DBP \<90 mmHg or mean sitting trough cuff SBP \<140 mmHg (off antihypertensive medication).
* Subjects with uncontrolled hypertension taking multiple antihypertensive therapies (at the discretion of the investigator).
* Signs or symptoms which could exacerbate the occurrence of hypotension such as volume and salt depletion.
* History of hypertensive encephalopathy, stroke or transient ischemic attack (TIA).
* Participation in another clinical trial involving an investigational drug within one month prior to screening.
* History of myocardial infarction, percutaneous transluminal coronary revascularization, coronary artery bypass graft, and/or unstable angina within the past 6 months.
* Any history of New York Heart Association Class III or IV congestive heart failure (CHF). A history of New York Heart Association Class I or II CHF may be exclusionary at the discretion of the investigator.
* History of secondary hypertension including renal disease, pheochromocytoma, or Cushing's syndrome.
* Uncorrected coarctation of the aorta, bilateral renal artery stenosis, or unilateral renal artery stenosis in a solitary kidney.
* Evidence of symptomatic resting bradycardia.
* Evidence of hemodynamically significant cardiac valvular disease.
* Presence of heart block greater than first degree atrioventricular block, chronic atrial fibrillation or flutter.
* Uncontrolled Type I or Type II diabetes defined as HbA1c \>9.0%. Diabetics must have documentation of HbA1c within 6 months of the Screening Visit. Undocumented subjects must have their HbA1c assessed prior to randomization. Note: Subjects with Type I or Type II diabetes controlled with insulin, diet or oral hypoglycemic agents on a stable dose for at least 30 days may be included.
* Evidence of liver disease as indicated by ALT and AST and/or total bilirubin \>3 times the upper limit of normal.
* Severe renal insufficiency defined as a creatinine clearance (based on the Cockcroft-Gault formula) of \<30 mL/min.
* Clinically significant laboratory elevations at Visit 1 that compromise subject safety, based on the investigator's judgment. Consideration should take into account the potential laboratory effects of the component blinded therapies.
* Positive for any one of the following tests: hepatitis B surface antigen, hepatitis C antibody (confirmed by radio immunobinding assay, RIBA) or HIV antibody (confirmed by western blot assay).
* Subjects with malignancy during the past 2 years excluding squamous cell or basal cell carcinoma of the skin.
* Known allergy to any of the medications used in the study.
* Subjects who require or are taking any concomitant medication, which may interfere with the objectives of the study (Refer to Section 5.2 for a listing of excluded medications).
* Pregnant or lactating females.
* Current history of drug or alcohol abuse.
* A subject with any medical condition, which in the judgment of the Investigator would jeopardize the evaluation of efficacy or safety and/or constitute a significant safety risk to the subject.

Primary outcomes:
measure: Change From Baseline to Week 12 in Seated Diastolic Blood Pressure (SeDBP).
timeFrame: baseline to 12 weeks
Secondary outcomes:
measure: Percentage of Subjects Who Reached Blood Pressure Goal (<140/90 mmHg; <130/80 mmHg for Subjects With Diabetes, Chronic Renal Disease, or Chronic Cardiovascular Disease)by 12 Weeks
timeFrame: Baseline to 12 weeks
measure: Change in Mean 24-hour Ambulatory Blood Pressure From Baseline to Week 12 or Early Termination
timeFrame: Baseline to 12 weeks or early termination
measure: Change in Seated Systolic Blood Pressure From Baseline to Week 12
timeFrame: Baseline to week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Columbiana
country: United States
state: Alabama
city: Gulf Shores
country: United States
state: Alabama
city: Hoover
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Montgomery
country: United States
state: Alabama
city: Muscle Shoals
country: United States
state: Alabama
city: Tuscumbia
country: United States
state: Alabama
city: Chandler
country: United States
state: Arizona
city: Goodyear
country: United States
state: Arizona
city: Lake Havasu City
country: United States
state: Arizona
city: Mesa
country: United States
state: Arizona
city: Peoria
country: United States
state: Arizona
city: Phoenix
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Hot Springs
country: United States
state: Arkansas
city: Jonesboro
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: North Little Rock
country: United States
state: Arkansas
city: Searcy
country: United States
state: Arkansas
city: Anaheim
country: United States
state: California
city: Beverly Hills
country: United States
state: California
city: Buena Park
country: United States
state: California
city: Burbank
country: United States
state: California
city: Carmichael
country: United States
state: California
city: Chino
country: United States
state: California
city: Chula Vista
country: United States
state: California
city: Escondido
country: United States
state: California
city: Greenbrae
country: United States
state: California
city: Hollywood
country: United States
state: California
city: Huntington Park
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Gatos
country: United States
state: California
city: Merced
country: United States
state: California
city: National City
country: United States
state: California
city: Orange
country: United States
state: California
city: Roseville
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Jose
country: United States
state: California
city: Santa Ana
country: United States
state: California
city: Santa Monica
country: United States
state: California
city: Temecula
country: United States
state: California
city: West Palm Beach
country: United States
state: California
city: Westlake Village
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Golden
country: United States
state: Colorado
city: Pueblo
country: United States
state: Colorado
city: Wheat Ridge
country: United States
state: Colorado
city: Danbury
country: United States
state: Connecticut
city: Milford
country: United States
state: Connecticut
city: Stamford
country: United States
state: Connecticut
city: Trumbull
country: United States
state: Connecticut
city: Waterbury
country: United States
state: Connecticut
city: Aventura
country: United States
state: Florida
city: Boynton Beach
country: United States
state: Florida
city: Bradenton
country: United States
state: Florida
city: Brooksville
country: United States
state: Florida
city: Cape Coral
country: United States
state: Florida
city: Clearwater
country: United States
state: Florida
city: Coral Gables
country: United States
state: Florida
city: Crystal River
country: United States
state: Florida
city: Daytona Beach
country: United States
state: Florida
city: Deerfield Beach
country: United States
state: Florida
city: DeLand
country: United States
state: Florida
city: Delray Beach
country: United States
state: Florida
city: Dunnellon
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Hollywood
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Jupiter
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Largo
country: United States
state: Florida
city: Merritt Island
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Ocala
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Pembroke Pines
country: United States
state: Florida
city: Plantation
country: United States
state: Florida
city: Port Orange
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: South Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: W. Bradenton
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Augusta
country: United States
state: Georgia
city: Columbus
country: United States
state: Georgia
city: Savannah
country: United States
state: Georgia
city: Suwanee
country: United States
state: Georgia
city: Waycross
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Gurnee
country: United States
state: Illinois
city: Libertyville
country: United States
state: Illinois
city: Evansville
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Newton
country: United States
state: Kansas
city: Shawnee Mission
country: United States
state: Kansas
city: Wichita
country: United States
state: Kansas
city: Madisonville
country: United States
state: Kentucky
city: Mount Sterling
country: United States
state: Kentucky
city: Munfordville
country: United States
state: Kentucky
city: Paducah
country: United States
state: Kentucky
city: Kenner
country: United States
state: Louisiana
city: Lake Charles
country: United States
state: Louisiana
city: Metairie
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Shreveport
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Elkridge
country: United States
state: Maryland
city: Oxon Hill
country: United States
state: Maryland
city: Brockton
country: United States
state: Massachusetts
city: Haverhill
country: United States
state: Massachusetts
city: West Yarmouth
country: United States
state: Massachusetts
city: Benzonia
country: United States
state: Michigan
city: Clarkston
country: United States
state: Michigan
city: Paw Paw
country: United States
state: Michigan
city: Southfield
country: United States
state: Michigan
city: Traverse City
country: United States
state: Michigan
city: Waterford
country: United States
state: Michigan
city: Brooklyn Center
country: United States
state: Minnesota
city: Chaska
country: United States
state: Minnesota
city: Saint Paul
country: United States
state: Minnesota
city: Olive Branch
country: United States
state: Mississippi
city: Florissant
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Butte
country: United States
state: Montana
city: Missoula
country: United States
state: Montana
city: Broken Bow
country: United States
state: Nebraska
city: North Platte
country: United States
state: Nebraska
city: Las Vegas
country: United States
state: Nevada
city: Berlin
country: United States
state: New Jersey
city: Elizabeth
country: United States
state: New Jersey
city: Voorhees
country: United States
state: New Jersey
city: Buffalo
country: United States
state: New York
city: Manlius
country: United States
state: New York
city: Mineola
country: United States
state: New York
city: New York
country: United States
state: New York
city: Westfield
country: United States
state: New York
city: Calabash
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Hickory
country: United States
state: North Carolina
city: High Point
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Salisbury
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Tabor City
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Fargo
country: United States
state: North Dakota
city: Austintown
country: United States
state: Ohio
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Euclid
country: United States
state: Ohio
city: Franklin
country: United States
state: Ohio
city: Kettering
country: United States
state: Ohio
city: Lyndhurst
country: United States
state: Ohio
city: Marion
country: United States
state: Ohio
city: Mount Gilead
country: United States
state: Ohio
city: Wadsworth
country: United States
state: Ohio
city: Westlake
country: United States
state: Ohio
city: Norman
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Eugene
country: United States
state: Oregon
city: Medford
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Beaver
country: United States
state: Pennsylvania
city: Bensalem
country: United States
state: Pennsylvania
city: Downingtown
country: United States
state: Pennsylvania
city: Erie
country: United States
state: Pennsylvania
city: Harleysville
country: United States
state: Pennsylvania
city: Jenkintown
country: United States
state: Pennsylvania
city: Jersey Shore
country: United States
state: Pennsylvania
city: Penndel
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Cranston
country: United States
state: Rhode Island
city: East Providence
country: United States
state: Rhode Island
city: Providence
country: United States
state: Rhode Island
city: Anderson
country: United States
state: South Carolina
city: Charleston
country: United States
state: South Carolina
city: Columbia
country: United States
state: South Carolina
city: Murrells Inlet
country: United States
state: South Carolina
city: Orangeburg
country: United States
state: South Carolina
city: Rapid City
country: United States
state: South Dakota
city: Bristol
country: United States
state: Tennessee
city: Fayetteville
country: United States
state: Tennessee
city: Knoxville
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: New Tazewell
country: United States
state: Tennessee
city: Tullahoma
country: United States
state: Tennessee
city: Austin
country: United States
state: Texas
city: Bedford
country: United States
state: Texas
city: Corpus Christi
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Hurst
country: United States
state: Texas
city: Lake Jackson
country: United States
state: Texas
city: Midland
country: United States
state: Texas
city: Plano
country: United States
state: Texas
city: Round Rock
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Spring
country: United States
state: Texas
city: Sugar Land
country: United States
state: Texas
city: Temple
country: United States
state: Texas
city: Waco
country: United States
state: Texas
city: Bountiful
country: United States
state: Utah
city: Magna
country: United States
state: Utah
city: Midvale
country: United States
state: Utah
city: Salt Lake City
country: United States
state: Utah
city: Sandy
country: United States
state: Utah
city: Saratoga Springs
country: United States
state: Utah
city: West Jordan
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Richmond
country: United States
state: Virginia
city: Suffolk
country: United States
state: Virginia
city: Federal Way
country: United States
state: Washington
city: Lakewood
country: United States
state: Washington
city: Tacoma
country: United States
state: Washington
city: Kenosha
country: United States
state: Wisconsin
city: Madison
country: United States
state: Wisconsin
city: Ciales
country: Puerto Rico
city: Guayama
country: Puerto Rico
city: Ponce
country: Puerto Rico
city: Rio Piedras
country: Puerto Rico
Study officials:
References:
citation: Kereiakes DJ, Chrysant SG, Izzo JL Jr, Littlejohn T 3rd, Melino M, Lee J, Fernandez V, Heyrman R. Olmesartan/amlodipine/hydrochlorothiazide in participants with hypertension and diabetes, chronic kidney disease, or chronic cardiovascular disease: a subanalysis of the multicenter, randomized, double-blind, parallel-group TRINITY study. Cardiovasc Diabetol. 2012 Oct 30;11:134. doi: 10.1186/1475-2840-11-134.
citation: Chrysant SG, Littlejohn T 3rd, Izzo JL Jr, Kereiakes DJ, Oparil S, Melino M, Lee J, Fernandez V, Heyrman R. Triple-Combination therapy with olmesartan, amlodipine, and hydrochlorothiazide in black and non-black study participants with hypertension: the TRINITY randomized, double-blind, 12-week, parallel-group study. Am J Cardiovasc Drugs. 2012 Aug 1;12(4):233-43. doi: 10.1007/BF03261832.
citation: Oparil S, Melino M, Lee J, Fernandez V, Heyrman R. Triple therapy with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide in adult patients with hypertension: The TRINITY multicenter, randomized, double-blind, 12-week, parallel-group study. Clin Ther. 2010 Jul;32(7):1252-69. doi: 10.1016/j.clinthera.2010.07.008.
citation: Chrysant SG, Oparil S, Melino M, Karki S, Lee J, Heyrman R. Efficacy and safety of long-term treatment with the combination of amlodipine besylate and olmesartan medoxomil in patients with hypertension. J Clin Hypertens (Greenwich). 2009 Sep;11(9):475-82. doi: 10.1111/j.1751-7176.2009.00159.x.