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The COREG And Lisinopril Combination Therapy In Hypertensive Subjects (COSMOS) Trial

NCT ID: NCT00347360

Last Updated: 2016-12-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

654 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-07-31

Study Completion Date

2008-04-30

Brief Summary

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This is a randomized, double-blind, double-dummy, parallel group trial employing 15 cells of a 4x4 factorial design (no placebo)to compare the hypertensive effects in patients with Stage 1 and Stage 2 hypertension of carvedilol (20, 40 or 80 mg daily) alone, lisinopril (10, 20 or 40 mg daily) alone, and all combinations of the doses.

Detailed Description

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A Randomized, Double-Blind, Double-Dummy, Parallel Group, Factorial Design Trial to Assess the Efficacy and Safety of up to Six Weeks Treatment with 20mg, 40mg, or 80mg QD Doses of Carvedilol Controlled Release Formulation (COREG CR) or 10mg, 20mg, or 40mg QD Doses of Lisinopril (ZESTRIL) or a Combination of One of the Doses of Each Medication

Conditions

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Hypertension

Keywords

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carvedilol hypertension lisinopril factorial

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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lisinopril

lisinopril

Group Type EXPERIMENTAL

lisinopril

Intervention Type DRUG

carvedilol

carvedilol controlled release formulation

Group Type EXPERIMENTAL

carvedilol controlled release formulation

Intervention Type DRUG

Interventions

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lisinopril

Intervention Type DRUG

carvedilol controlled release formulation

Intervention Type DRUG

Other Intervention Names

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lisinopril

Eligibility Criteria

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Inclusion Criteria

* Subject has given signed informed consent.
* Subject is male or female 18 years of age at the time informed consent is signed.
* At the Screening visit, subject has a documented history or current presentation with stage 1 or stage 2 hypertension (see Section 15.1, Appendix 1 and Section 15.4, Appendix 4) which meets one of the following criteria. Note: All blood pressures are mean sitting cuff pressures:

Documented history of hypertension and receiving two antihypertensive medications with mean sDBP \<90 mmHg or for diabetic subjects (defined as having an established diagnosis of diabetes or receiving treatment for diabetes), mean sDBP \<80 mmHg. Subjects taking beta blockers, clonidine, or other antihypertensive medications where abrupt discontinuation would be of clinical concern must be tapered off the medication during the Washout/Placebo Run-in phase to avoid rebound hypertension. All subjects must be able to be safely withdrawn from all antihypertensive treatment during the Washout/Placebo Run-in phase. Subjects should not be enrolled if the investigator thinks it is likely the subject's mean sDBP will exceed 109 mmHg or their mean sSBP will exceed 180 mmHg during the Washout/Placebo Run-in phase (NOTE: A combination drug containing two antihypertensive agents represents two antihypertensive medications \[e.g., Hyzaar is losartan potassium AND hydrochlorothiazide, therefore, counts as two antihypertensive medications\].) OR Receiving one antihypertensive medication with mean sDBP =109 mmHg and can be safely withdrawn from all antihypertensive medication during the Washout/Placebo Run-in phase. Any subject who is receiving beta-blockers, clonidine, or other antihypertensive medications where abrupt discontinuation would be of clinical concern must have the dose tapered down during the Washout/Placebo Run-in phase to avoid rebound hypertension. All subjects must be able to be safely withdrawn from all antihypertensive treatment during the Washout/Placebo Run-in phase. Subjects should not be enrolled if the investigator thinks it is likely the subject's mean sDBP will exceed 109 mmHg or their mean sSBP will exceed 180 mmHg during the Washout/Placebo Run-in phase.

(NOTE: A combination drug containing two antihypertensive agents represents two antihypertensive medications \[e.g., Hyzaar is losartan potassium AND hydrochlorothiazide, therefore, counts as two antihypertensive medications\].

OR Untreated/newly diagnosed subjects: mean sDBP =95 and =109, or for diabetic subjects, mean sDBP =85 and =109 (see Section 15.1, Appendix 1). If newly diagnosed, must have qualifying blood pressure confirmed on two consecutive visits with the mean sDBP value not differing more than 8 mmHg. (Previously untreated subjects include subjects who have not been treated for hypertension in the last two months.).

* At Baseline:

DAY BEFORE RANDOMIZATION: Prior to having the baseline ABPM equipment placed, subject has mean sitting cuff DBP that is ≥93 and ≤111 mmHg (or for diabetic subjects, ≥83 and ≤111 mmHg). Subjects who were taking antihypertensive medication at Screening and do not meet this criterion after one week (or 5 half-lives, whichever is longer), can return in one week ±1day and have his/her blood pressure evaluated again for this inclusion criterion.

AND

RANDOMIZATON DAY: After completion of the ABPM assessment, subject meets the following ABPM (both 12 hr and 24 hr) criteria (see Section 15.1, Appendix 1):

* Mean 12-hour daytime (9 AM to 9 PM) DBP ≥90 and ≤109mmHg (or for diabetic subjects, ≥80 and ≤109mmHg)
* At least 75% of the programmed readings properly recorded over 24-hour monitoring period
* No more than two non-consecutive hours with less than two successful readings per hour while awake, and no more than two consecutive hours with less than one successful reading per hour during the sleep period over the 24-hour monitoring period
* At least two successful readings per hour for three of the last four hours of recording (trough period i.e., 20-24 hour during which subjects must be awake) with a total of at least 7 successful readings over this period.

Exclusion Criteria

* Subject is taking ≥3 antihypertensive medications. (NOTE: A combination drug containing two antihypertensive agents represents two antihypertensive medications \[e.g., Hyzaar is losartan potassium AND hydrochlorothiazide, therefore, counts as two antihypertensive medications\].)
* Subject has DBP =90 mmHg (or for diabetic subjects, DBP =80 mmHg) on two antihypertensive medications.
* Subject has any known contraindication to ACE inhibitors (e.g., ACE-induced cough, angioedema or negative renal effects), or blocker treatment.
* Hyperkalemia or history of hyperkalemia resulting from either Type IV RTA (renal tubular acidosis) or previous ACEi therapy.
* Is female of childbearing potential. NOTE: Female subjects who are postmenopausal (i.e., no menstrual period for a minimum of 12 months prior to Screening) or surgically sterilized are eligible for the study. If judged appropriate, a postmenopausal woman may be required to have a documented negative urine pregnancy test.
* Subject has malignant (accelerated) hypertension, history of malignant hypertension, or secondary forms of hypertension.
* Subject has mean sitting SBP =180 mmHg.
* Subject has advanced hypertensive retinopathy (Keith Wagner Grade IV).
* Subject has Type 1 diabetes mellitus, or those with Type 2 having HbA1c ≥9% at Screening.
* Subject has uncorrected primary obstructive or severe regurgitative valvular disease, nondilated (restrictive) or hypertrophic cardiomyopathies.
* Subject has any of the following conditions:

uncontrollable or symptomatic arrhythmias unstable angina or angina treated with a beta-blocker sick sinus syndrome or second or third degree heart block (unless treated with a permanent, functioning pacemaker) bradycardia (sitting heart rate \<55 bpm) history of myocardial infarction stroke within 3 months of Screening

* Subject is in atrial fibrillation.
* Subject has Congestive Heart Failure NYHA (New York Heart Association) class II-IV \[The Criteria Committee of the New York Heart Association, 1994\].
* Current clinical evidence of asthma or chronic obstructive pulmonary disease (e.g., severe emphysema or chronic bronchitis) requiring long term use of inhaled oral bronchodilator or steroid drug therapy; also subjects with a history of bronchospastic disease not undergoing active therapy in whom, in the investigator's opinion, treatment with the study medication could provoke bronchospasm; or requirement for or anticipated treatment with beta-2 agonist therapy (e.g., albuterol \[Ventolin, Proventil\], metaproterenol \[Alupent\], pirbuterol \[Maxair\], terbutaline \[Brethaire\], isoetharine \[Bronkosol\], and Levalbuterol \[Xopenex\]).
* Subject has evidence of any of the following clinically significant diseases that could impair the absorption, metabolism, or excretion of orally-administered medication:

renal disease defined as estimated Glomerular Filtration Rate (eGFR) \<30mL/min per 1.73 m2 hepatic disease (i.e., ALT or AST levels greater than three times the upper limit of normal range, history of hepatic impairment, or by clinical assessment) chronic biliary disorders gastric bypass surgery

* Subject has endocrine disorders that affect blood pressure (e.g., pheochromocytoma, active and untreated hypo- or hyperthyroidism).
* Subject has systemic disease, including cancer, with reduced (\<12 months) life expectancy.
* Subject has used an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding Screening.
* Subject has a history of a psychological illness/condition that would interfere with their ability to understand or complete the requirements of the study.
* Subject has any condition that, in the opinion of the Investigator and/or the GSK Medical Monitor, places the subject at an unacceptable risk as a participant in this trial.
* Subject is receiving ongoing treatment or is anticipated to receive treatment with any of the following medications during treatment with double blind study medication:

any antihypertensive medication except for assigned study medication. This would include alpha blockers or other medications that may be used to treat hypertension and other conditions unrelated to hypertension; monoamine oxidase (MAO) inhibitors; any Class I or III antiarrhythmic; beta-2-agonists.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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Anniston, Alabama, United States

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Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Birmingham, Alabama, United States

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Haleyville, Alabama, United States

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Mobile, Alabama, United States

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Muscle Shoals, Alabama, United States

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Chandler, Arizona, United States

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Gilbert, Arizona, United States

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Glendale, Arizona, United States

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Mesa, Arizona, United States

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Phoenix, Arizona, United States

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Phoenix, Arizona, United States

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Phoenix, Arizona, Arizona, United States

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Scottsdale, Arizona, United States

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Scottsdale, Arizona, United States

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Sun City, Arizona, United States

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Tucson, Arizona, United States

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Tucson, Arizona, United States

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Little Rock, Arkansas, United States

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Searcy, Arkansas, United States

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Beuna Park, California, United States

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Beverly Hills, California, United States

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Burbank, California, United States

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Carlsbad, California, United States

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Fountain Valley, California, United States

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Fresno, California, United States

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Loma Linda, California, United States

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Mission Viejo, California, United States

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Pico Rivera, California, United States

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Rancho Cordova, California, United States

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San Diego, California, United States

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San Diego, California, United States

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Santa Ana, California, United States

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Vista, California, United States

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Walnut Creek, California, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Wilmington, Delaware, United States

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Washington D.C., District of Columbia, United States

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Coral Gables, Florida, United States

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Hialeah, Florida, United States

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Hollywood, Florida, United States

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Jacksonville, Florida, United States

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Jacksonville Beach, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Palm Harbor, Florida, United States

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Pembroke Pines, Florida, United States

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Pembroke Pines, Florida, United States

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Sarasota, Florida, United States

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West Palm Beach, Florida, United States

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Gainesville, Georgia, United States

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Marietta, Georgia, United States

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Sandersville, Georgia, United States

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Savannah, Georgia, United States

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Aurora, Illinois, United States

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Chicago, Illinois, United States

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Chicago, Illinois, United States

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Melrose Park, Illinois, United States

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Avon, Indiana, United States

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Bloomington, Indiana, United States

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Fort Wayne, Indiana, United States

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Indianapolis, Indiana, United States

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Ames, Iowa, United States

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Wichita, Kansas, United States

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Slidell, Louisiana, United States

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Springfield, Massachusetts, United States

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Taunton, Massachusetts, United States

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Bingham Farms, Michigan, United States

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Brooklyn Center, Minnesota, United States

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Missoula, Montana, United States

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O Fallon, Montana, United States

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Omaha, Nebraska, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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Las Vegas, Nevada, United States

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Cherry Hill, New Jersey, United States

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Edison, New Jersey, United States

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Ridgewood, New Jersey, United States

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Voorhees Township, New Jersey, United States

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Albuquerque, New Mexico, United States

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Brooklyn, New York, United States

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Buffalo, New York, United States

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Kingston, New York, United States

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Lewinston, New York, United States

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Tonawanda, New York, United States

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Asheville, North Carolina, United States

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Charlotte, North Carolina, United States

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High Point, North Carolina, United States

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Raleigh, North Carolina, United States

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Fargo, North Dakota, United States

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Cincinnati, Ohio, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Cleveland, Ohio, United States

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Dayton, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Tulsa, Oklahoma, United States

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Eugene, Oregon, United States

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Beaver, Pennsylvania, United States

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Doylestown, Pennsylvania, United States

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Erie, Pennsylvania, United States

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Havertown, Pennsylvania, United States

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Landsdale, Pennsylvania, United States

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Leetsdale, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Warminster, Pennsylvania, United States

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West Chester, Pennsylvania, United States

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Beaufort, South Carolina, United States

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Charleston, South Carolina, United States

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Columbia, South Carolina, United States

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Gaffney, South Carolina, United States

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Greer, South Carolina, United States

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Hilton Head Island, South Carolina, United States

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Manning, South Carolina, United States

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Simpsonville, South Carolina, United States

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Spartanburg, South Carolina, United States

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Sumter, South Carolina, United States

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Taylors, South Carolina, United States

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Union, South Carolina, United States

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Clarksville, Tennessee, United States

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Jackson, Tennessee, United States

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Johnson City, Tennessee, United States

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Nashville, Tennessee, United States

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Selmer, Tennessee, United States

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Arlington, Texas, United States

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Austin, Texas, United States

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Georgetown, Texas, United States

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Grand Prairie/Texas, Texas, United States

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Houston, Texas, United States

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Longview, Texas, United States

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San Antonio, Texas, United States

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San Antonio, Texas, United States

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Sugar Land, Texas, United States

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Temple, Texas, United States

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Waco, Texas, United States

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Murray, Utah, United States

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Salt Lake City, Utah, United States

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Sandy City, Utah, United States

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Arlington, Virginia, United States

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Burke, Virginia, United States

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Chester, Virginia, United States

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Fairfax, Virginia, United States

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Manassas, Virginia, United States

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Spokane, Washington, United States

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Tacoma, Washington, United States

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Milwaukee, Wisconsin, United States

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Countries

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United States

References

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Bakris GL, Iyengar M, Lukas MA, Ordronneau P, Weber MA. Effect of combining extended-release carvedilol and lisinopril in hypertension: results of the COSMOS study. J Clin Hypertens (Greenwich). 2010 Sep;12(9):678-86. doi: 10.1111/j.1751-7176.2010.00341.x. Epub 2010 Jul 8.

Reference Type DERIVED
PMID: 20883227 (View on PubMed)

Study Documents

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Document Type: Informed Consent Form

View Document

Document Type: Annotated Case Report Form

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Individual Participant Data Set

View Document

Document Type: Study Protocol

View Document

Document Type: Clinical Study Report

View Document

Document Type: Dataset Specification

View Document

Related Links

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https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

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CFD105453

Identifier Type: -

Identifier Source: org_study_id