The COREG And Lisinopril Combination Therapy In Hypertensive Subjects (COSMOS) Trial
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
1 other identifier
interventional
654
1 country
151
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 hypertension
Started Jul 2006
Typical duration for phase_3 hypertension
151 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 29, 2006
CompletedStudy Start
First participant enrolled
July 1, 2006
CompletedFirst Posted
Study publicly available on registry
July 4, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2008
CompletedResults Posted
Study results publicly available
November 9, 2009
CompletedDecember 26, 2016
November 1, 2016
1.8 years
June 29, 2006
April 22, 2009
November 3, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Change From Baseline to Week 6 in 24 Hour (hr) Mean Diastolic Blood Pressure
Ambulatory blood pressure monitoring (ABPM) was completed at Baseline and at the end of treatment/Week 6 or early withdrawal by standard electronic ABPM equipment worn by the subject for 24-hr of ambulatory activity. The 24 hr assessment period started at the time of the first reading and ended exactly 24 hr later on the following day. Data collected included mean diastolic blood pressure (DBP).
Baseline, Week 6.
Change From Baseline to Week 6 in Trough Diastolic Blood Pressure
Trough ABPM was the average across 20-24 hr after dosing for each subject.
Baseline, Week 6
Secondary Outcomes (10)
Change From Baseline to Week 6 in 24 Hour Mean Systolic Blood Pressure
Baseline, Week 6
Change From Baseline to Week 6 in Trough Systolic Blood Pressure
Baseline, Week 6
Dose-response Treatment Estimates: Change From Baseline to Week 6 in 24 Hour Mean DBP by ABPM (Ambulatory Blood Pressure Monitoring)
Baseline, Week 6
Change From Baseline to Week 6 in Trough to Peak Ratios of DBP by 24 Hour ABPM (Ambulatory Blood Pressure Monitoring)
Baseline, Week 6
Overall Description of Safety in Each Treatment Group Using Adverse Events, Laboratory Evaluations, ECG Changes, Vital Sign Changes, and Withdrawal Rates.
Weeks 1 through 48
- +5 more secondary outcomes
Study Arms (2)
lisinopril
EXPERIMENTALlisinopril
carvedilol
EXPERIMENTALcarvedilol controlled release formulation
Interventions
Eligibility Criteria
You may qualify if:
- 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:
- 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.
You may not qualify if:
- 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 \[Xopenex\]).
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (151)
GSK Investigational Site
Anniston, Alabama, 36207, United States
GSK Investigational Site
Birmingham, Alabama, 35215, United States
GSK Investigational Site
Birmingham, Alabama, 35216, United States
GSK Investigational Site
Birmingham, Alabama, 35235, United States
GSK Investigational Site
Birmingham, Alabama, 35242, United States
GSK Investigational Site
Haleyville, Alabama, 35565, United States
GSK Investigational Site
Mobile, Alabama, 36617, United States
GSK Investigational Site
Muscle Shoals, Alabama, 35662, United States
GSK Investigational Site
Chandler, Arizona, 85225, United States
GSK Investigational Site
Gilbert, Arizona, 85296, United States
GSK Investigational Site
Glendale, Arizona, 85308, United States
GSK Investigational Site
Mesa, Arizona, 85206, United States
GSK Investigational Site
Phoenix, Arizona, 85023, United States
GSK Investigational Site
Phoenix, Arizona, 85032, United States
GSK Investigational Site
Phoenix, Arizona, Arizona, 86106, United States
GSK Investigational Site
Scottsdale, Arizona, 85251, United States
GSK Investigational Site
Scottsdale, Arizona, 85260, United States
GSK Investigational Site
Sun City, Arizona, 85351, United States
GSK Investigational Site
Tucson, Arizona, 85712, United States
GSK Investigational Site
Tucson, Arizona, 85741, United States
GSK Investigational Site
Little Rock, Arkansas, 72204, United States
GSK Investigational Site
Searcy, Arkansas, 72143, United States
GSK Investigational Site
Beuna Park, California, 90620, United States
GSK Investigational Site
Beverly Hills, California, 90211, United States
GSK Investigational Site
Burbank, California, 91505, United States
GSK Investigational Site
Carlsbad, California, 92008, United States
GSK Investigational Site
Fountain Valley, California, 92708, United States
GSK Investigational Site
Fresno, California, 93703, United States
GSK Investigational Site
Loma Linda, California, 92354, United States
GSK Investigational Site
Mission Viejo, California, 92691, United States
GSK Investigational Site
Pico Rivera, California, 90660, United States
GSK Investigational Site
Rancho Cordova, California, 95670, United States
GSK Investigational Site
San Diego, California, 92117, United States
GSK Investigational Site
San Diego, California, 92128, United States
GSK Investigational Site
Santa Ana, California, 92705, United States
GSK Investigational Site
Vista, California, 92084, United States
GSK Investigational Site
Walnut Creek, California, 94598, United States
GSK Investigational Site
Colorado Springs, Colorado, 80904, United States
GSK Investigational Site
Denver, Colorado, 80206, United States
GSK Investigational Site
Wilmington, Delaware, 19805, United States
GSK Investigational Site
Washington D.C., District of Columbia, 20017, United States
GSK Investigational Site
Coral Gables, Florida, 33134, United States
GSK Investigational Site
Hialeah, Florida, 33013, United States
GSK Investigational Site
Hollywood, Florida, 33023, United States
GSK Investigational Site
Jacksonville, Florida, 32205, United States
GSK Investigational Site
Jacksonville Beach, Florida, 32250, United States
GSK Investigational Site
Miami, Florida, 33156, United States
GSK Investigational Site
Miami, Florida, 33169, United States
GSK Investigational Site
Palm Harbor, Florida, 34684, United States
GSK Investigational Site
Pembroke Pines, Florida, 33024, United States
GSK Investigational Site
Pembroke Pines, Florida, 33027, United States
GSK Investigational Site
Sarasota, Florida, 34239, United States
GSK Investigational Site
West Palm Beach, Florida, 33409, United States
GSK Investigational Site
Gainesville, Georgia, 30501, United States
GSK Investigational Site
Marietta, Georgia, 30066, United States
GSK Investigational Site
Sandersville, Georgia, 31082, United States
GSK Investigational Site
Savannah, Georgia, 31406, United States
GSK Investigational Site
Aurora, Illinois, 60504, United States
GSK Investigational Site
Chicago, Illinois, 60607, United States
GSK Investigational Site
Chicago, Illinois, 60610, United States
GSK Investigational Site
Melrose Park, Illinois, 60160, United States
GSK Investigational Site
Avon, Indiana, 46123, United States
GSK Investigational Site
Bloomington, Indiana, 47102, United States
GSK Investigational Site
Fort Wayne, Indiana, 46804, United States
GSK Investigational Site
Indianapolis, Indiana, 46250, United States
GSK Investigational Site
Ames, Iowa, 50010, United States
GSK Investigational Site
Wichita, Kansas, 67205, United States
GSK Investigational Site
Slidell, Louisiana, 70458, United States
GSK Investigational Site
Springfield, Massachusetts, 01103, United States
GSK Investigational Site
Taunton, Massachusetts, 02780., United States
GSK Investigational Site
Bingham Farms, Michigan, 48025, United States
GSK Investigational Site
Brooklyn Center, Minnesota, 55430, United States
GSK Investigational Site
Missoula, Montana, 59808, United States
GSK Investigational Site
O Fallon, Montana, 63366, United States
GSK Investigational Site
Omaha, Nebraska, 68131, United States
GSK Investigational Site
Las Vegas, Nevada, 89016, United States
GSK Investigational Site
Las Vegas, Nevada, 89119, United States
GSK Investigational Site
Las Vegas, Nevada, 89128, United States
GSK Investigational Site
Cherry Hill, New Jersey, 08034, United States
GSK Investigational Site
Edison, New Jersey, 08817, United States
GSK Investigational Site
Ridgewood, New Jersey, 7450, United States
GSK Investigational Site
Voorhees Township, New Jersey, 08043, United States
GSK Investigational Site
Albuquerque, New Mexico, 87102, United States
GSK Investigational Site
Brooklyn, New York, 11203, United States
GSK Investigational Site
Buffalo, New York, 14215, United States
GSK Investigational Site
Kingston, New York, 12401, United States
GSK Investigational Site
Lewinston, New York, 14092, United States
GSK Investigational Site
Tonawanda, New York, 14150-1810, United States
GSK Investigational Site
Asheville, North Carolina, 28801, United States
GSK Investigational Site
Charlotte, North Carolina, 28211, United States
GSK Investigational Site
High Point, North Carolina, 27262, United States
GSK Investigational Site
Raleigh, North Carolina, 27615, United States
GSK Investigational Site
Fargo, North Dakota, 58103, United States
GSK Investigational Site
Cincinnati, Ohio, 45219, United States
GSK Investigational Site
Cincinnati, Ohio, 45236, United States
GSK Investigational Site
Cleveland, Ohio, 44106, United States
GSK Investigational Site
Cleveland, Ohio, 44195, United States
GSK Investigational Site
Dayton, Ohio, 45406, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73103, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73112, United States
GSK Investigational Site
Tulsa, Oklahoma, 74104, United States
GSK Investigational Site
Eugene, Oregon, 97401, United States
GSK Investigational Site
Beaver, Pennsylvania, 15009, United States
GSK Investigational Site
Doylestown, Pennsylvania, 18901, United States
GSK Investigational Site
Erie, Pennsylvania, 16504, United States
GSK Investigational Site
Havertown, Pennsylvania, 19083, United States
GSK Investigational Site
Landsdale, Pennsylvania, 19446, United States
GSK Investigational Site
Leetsdale, Pennsylvania, 15056, United States
GSK Investigational Site
Philadelphia, Pennsylvania, 19152, United States
GSK Investigational Site
Philadelphia, Pennsylvania, 19154, United States
GSK Investigational Site
Warminster, Pennsylvania, 18974, United States
GSK Investigational Site
West Chester, Pennsylvania, 19380, United States
GSK Investigational Site
Beaufort, South Carolina, 29906, United States
GSK Investigational Site
Charleston, South Carolina, 29403, United States
GSK Investigational Site
Columbia, South Carolina, 29201, United States
GSK Investigational Site
Gaffney, South Carolina, 29340, United States
GSK Investigational Site
Greer, South Carolina, 29651, United States
GSK Investigational Site
Hilton Head Island, South Carolina, 29926, United States
GSK Investigational Site
Manning, South Carolina, 29102, United States
GSK Investigational Site
Simpsonville, South Carolina, 29681, United States
GSK Investigational Site
Spartanburg, South Carolina, 29303, United States
GSK Investigational Site
Sumter, South Carolina, 29150, United States
GSK Investigational Site
Taylors, South Carolina, 29687, United States
GSK Investigational Site
Union, South Carolina, 29309, United States
GSK Investigational Site
Clarksville, Tennessee, 37043, United States
GSK Investigational Site
Jackson, Tennessee, 38305, United States
GSK Investigational Site
Johnson City, Tennessee, 37601, United States
GSK Investigational Site
Nashville, Tennessee, 37203, United States
GSK Investigational Site
Selmer, Tennessee, 38375, United States
GSK Investigational Site
Arlington, Texas, 76014, United States
GSK Investigational Site
Austin, Texas, 78705, United States
GSK Investigational Site
Georgetown, Texas, 78626, United States
GSK Investigational Site
Grand Prairie/Texas, Texas, 5052, United States
GSK Investigational Site
Houston, Texas, 77081, United States
GSK Investigational Site
Longview, Texas, 75605, United States
GSK Investigational Site
San Antonio, Texas, 78224, United States
GSK Investigational Site
San Antonio, Texas, 78229, United States
GSK Investigational Site
Sugar Land, Texas, 77479, United States
GSK Investigational Site
Temple, Texas, 76502, United States
GSK Investigational Site
Waco, Texas, 76712, United States
GSK Investigational Site
Murray, Utah, 84107, United States
GSK Investigational Site
Salt Lake City, Utah, 84102, United States
GSK Investigational Site
Sandy City, Utah, 84094, United States
GSK Investigational Site
Arlington, Virginia, 22205, United States
GSK Investigational Site
Burke, Virginia, 22015, United States
GSK Investigational Site
Chester, Virginia, 23836, United States
GSK Investigational Site
Fairfax, Virginia, 22030, United States
GSK Investigational Site
Manassas, Virginia, 20110, United States
GSK Investigational Site
Spokane, Washington, 99206, United States
GSK Investigational Site
Tacoma, Washington, 98405, United States
GSK Investigational Site
Milwaukee, Wisconsin, 53209, United States
Related Publications (1)
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.
PMID: 20883227DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 29, 2006
First Posted
July 4, 2006
Study Start
July 1, 2006
Primary Completion
April 1, 2008
Study Completion
April 1, 2008
Last Updated
December 26, 2016
Results First Posted
November 9, 2009
Record last verified: 2016-11
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.