HypertensionPhase 3NCT00347360
The COREG And Lisinopril Combination Therapy In Hypertensive Subjects (COSMOS) Trial
A Phase 3 study testing lisinopril in people with Hypertension, run by GlaxoSmithKline at 151 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- lisinopril
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 654 participants
- Where
- 151 sitesUnited States
- Study dates
- Jul 2006to Apr 2008
- 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
- 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 All subjects must be able to be safely withdrawn from all antihypertensive treatment during the Washout/Placebo Run-in phase.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.).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
151 sites in 1 country.
151 sites in 1 country
United States151 sites
GSK Investigational Site
Albuquerque, New Mexico, 87102
GSK Investigational Site
Ames, Iowa, 50010
GSK Investigational Site
Anniston, Alabama, 36207
GSK Investigational Site
Arlington, Texas, 76014
GSK Investigational Site
Arlington, Virginia, 22205
GSK Investigational Site
Asheville, North Carolina, 28801
GSK Investigational Site
Aurora, Illinois, 60504
GSK Investigational Site
Austin, Texas, 78705
GSK Investigational Site
Avon, Indiana, 46123
GSK Investigational Site
Beaufort, South Carolina, 29906
GSK Investigational Site
Beaver, Pennsylvania, 15009
GSK Investigational Site
Beuna Park, California, 90620
GSK Investigational Site
Beverly Hills, California, 90211
GSK Investigational Site
Bingham Farms, Michigan, 48025
GSK Investigational Site
Birmingham, Alabama, 35215
GSK Investigational Site
Birmingham, Alabama, 35216
GSK Investigational Site
Birmingham, Alabama, 35235
GSK Investigational Site
Birmingham, Alabama, 35242
GSK Investigational Site
Bloomington, Indiana, 47102
GSK Investigational Site
Brooklyn, New York, 11203
GSK Investigational Site
Brooklyn Center, Minnesota, 55430
GSK Investigational Site
Buffalo, New York, 14215
GSK Investigational Site
Burbank, California, 91505
GSK Investigational Site
Burke, Virginia, 22015
GSK Investigational Site
Carlsbad, California, 92008
GSK Investigational Site
Chandler, Arizona, 85225
GSK Investigational Site
Charleston, South Carolina, 29403
GSK Investigational Site
Charlotte, North Carolina, 28211
GSK Investigational Site
Cherry Hill, New Jersey, 08034
GSK Investigational Site
Chester, Virginia, 23836
GSK Investigational Site
Chicago, Illinois, 60607
GSK Investigational Site
Chicago, Illinois, 60610
GSK Investigational Site
Cincinnati, Ohio, 45219
GSK Investigational Site
Cincinnati, Ohio, 45236
GSK Investigational Site
Clarksville, Tennessee, 37043
GSK Investigational Site
Cleveland, Ohio, 44106
GSK Investigational Site
Cleveland, Ohio, 44195
GSK Investigational Site
Colorado Springs, Colorado, 80904
GSK Investigational Site
Columbia, South Carolina, 29201
GSK Investigational Site
Coral Gables, Florida, 33134
GSK Investigational Site
Dayton, Ohio, 45406
GSK Investigational Site
Denver, Colorado, 80206
GSK Investigational Site
Doylestown, Pennsylvania, 18901
GSK Investigational Site
Edison, New Jersey, 08817
GSK Investigational Site
Erie, Pennsylvania, 16504
GSK Investigational Site
Eugene, Oregon, 97401
GSK Investigational Site
Fairfax, Virginia, 22030
GSK Investigational Site
Fargo, North Dakota, 58103
GSK Investigational Site
Fort Wayne, Indiana, 46804
GSK Investigational Site
Fountain Valley, California, 92708
GSK Investigational Site
Fresno, California, 93703
GSK Investigational Site
Gaffney, South Carolina, 29340
GSK Investigational Site
Gainesville, Georgia, 30501
GSK Investigational Site
Georgetown, Texas, 78626
GSK Investigational Site
Gilbert, Arizona, 85296
GSK Investigational Site
Glendale, Arizona, 85308
GSK Investigational Site
Grand Prairie/Texas, Texas, 5052
GSK Investigational Site
Greer, South Carolina, 29651
GSK Investigational Site
Haleyville, Alabama, 35565
GSK Investigational Site
Havertown, Pennsylvania, 19083
GSK Investigational Site
Hialeah, Florida, 33013
GSK Investigational Site
High Point, North Carolina, 27262
GSK Investigational Site
Hilton Head Island, South Carolina, 29926
GSK Investigational Site
Hollywood, Florida, 33023
GSK Investigational Site
Houston, Texas, 77081
GSK Investigational Site
Indianapolis, Indiana, 46250
GSK Investigational Site
Jackson, Tennessee, 38305
GSK Investigational Site
Jacksonville, Florida, 32205
GSK Investigational Site
Jacksonville Beach, Florida, 32250
GSK Investigational Site
Johnson City, Tennessee, 37601
GSK Investigational Site
Kingston, New York, 12401
GSK Investigational Site
Landsdale, Pennsylvania, 19446
GSK Investigational Site
Las Vegas, Nevada, 89016
GSK Investigational Site
Las Vegas, Nevada, 89119
GSK Investigational Site
Las Vegas, Nevada, 89128
GSK Investigational Site
Leetsdale, Pennsylvania, 15056
GSK Investigational Site
Lewinston, New York, 14092
GSK Investigational Site
Little Rock, Arkansas, 72204
GSK Investigational Site
Loma Linda, California, 92354
GSK Investigational Site
Longview, Texas, 75605
GSK Investigational Site
Manassas, Virginia, 20110
GSK Investigational Site
Manning, South Carolina, 29102
GSK Investigational Site
Marietta, Georgia, 30066
GSK Investigational Site
Melrose Park, Illinois, 60160
GSK Investigational Site
Mesa, Arizona, 85206
GSK Investigational Site
Miami, Florida, 33156
GSK Investigational Site
Miami, Florida, 33169
GSK Investigational Site
Milwaukee, Wisconsin, 53209
GSK Investigational Site
Mission Viejo, California, 92691
GSK Investigational Site
Missoula, Montana, 59808
GSK Investigational Site
Mobile, Alabama, 36617
GSK Investigational Site
Murray, Utah, 84107
GSK Investigational Site
Muscle Shoals, Alabama, 35662
GSK Investigational Site
Nashville, Tennessee, 37203
GSK Investigational Site
O Fallon, Montana, 63366
GSK Investigational Site
Oklahoma City, Oklahoma, 73103
GSK Investigational Site
Oklahoma City, Oklahoma, 73112
GSK Investigational Site
Omaha, Nebraska, 68131
GSK Investigational Site
Palm Harbor, Florida, 34684
GSK Investigational Site
Pembroke Pines, Florida, 33024
GSK Investigational Site
Pembroke Pines, Florida, 33027
GSK Investigational Site
Philadelphia, Pennsylvania, 19152
GSK Investigational Site
Philadelphia, Pennsylvania, 19154
GSK Investigational Site
Phoenix, Arizona, 85023
GSK Investigational Site
Phoenix, Arizona, 85032
GSK Investigational Site
Phoenix, Arizona, Arizona, 86106
GSK Investigational Site
Pico Rivera, California, 90660
GSK Investigational Site
Raleigh, North Carolina, 27615
GSK Investigational Site
Rancho Cordova, California, 95670
GSK Investigational Site
Ridgewood, New Jersey, 7450
GSK Investigational Site
Salt Lake City, Utah, 84102
GSK Investigational Site
San Antonio, Texas, 78224
GSK Investigational Site
San Antonio, Texas, 78229
GSK Investigational Site
San Diego, California, 92117
GSK Investigational Site
San Diego, California, 92128
GSK Investigational Site
Sandersville, Georgia, 31082
GSK Investigational Site
Sandy City, Utah, 84094
GSK Investigational Site
Santa Ana, California, 92705
GSK Investigational Site
Sarasota, Florida, 34239
GSK Investigational Site
Savannah, Georgia, 31406
GSK Investigational Site
Scottsdale, Arizona, 85251
GSK Investigational Site
Scottsdale, Arizona, 85260
GSK Investigational Site
Searcy, Arkansas, 72143
GSK Investigational Site
Selmer, Tennessee, 38375
GSK Investigational Site
Simpsonville, South Carolina, 29681
GSK Investigational Site
Slidell, Louisiana, 70458
GSK Investigational Site
Spartanburg, South Carolina, 29303
GSK Investigational Site
Spokane, Washington, 99206
GSK Investigational Site
Springfield, Massachusetts, 01103
GSK Investigational Site
Sugar Land, Texas, 77479
GSK Investigational Site
Sumter, South Carolina, 29150
GSK Investigational Site
Sun City, Arizona, 85351
GSK Investigational Site
Tacoma, Washington, 98405
GSK Investigational Site
Taunton, Massachusetts, 02780.
GSK Investigational Site
Taylors, South Carolina, 29687
GSK Investigational Site
Temple, Texas, 76502
GSK Investigational Site
Tonawanda, New York, 14150-1810
GSK Investigational Site
Tucson, Arizona, 85712
GSK Investigational Site
Tucson, Arizona, 85741
GSK Investigational Site
Tulsa, Oklahoma, 74104
GSK Investigational Site
Union, South Carolina, 29309
GSK Investigational Site
Vista, California, 92084
GSK Investigational Site
Voorhees Township, New Jersey, 08043
GSK Investigational Site
Waco, Texas, 76712
GSK Investigational Site
Walnut Creek, California, 94598
GSK Investigational Site
Warminster, Pennsylvania, 18974
GSK Investigational Site
Washington D.C., District of Columbia, 20017
GSK Investigational Site
West Chester, Pennsylvania, 19380
GSK Investigational Site
West Palm Beach, Florida, 33409
GSK Investigational Site
Wichita, Kansas, 67205
GSK Investigational Site
Wilmington, Delaware, 19805
About this study
Official title: 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
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.
Read the detailed description
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
- Hypertension
- Being tested
- lisinopril, carvedilol controlled release formulation
- Keywords
- carvedilol, hypertension, lisinopril, factorial
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lisinoprilDrug
carvedilol controlled release formulationDrug
Also called lisinopril
| Study group | Role | What they receive |
|---|---|---|
| lisinopril | Experimental | lisinopril Receives: Drug: lisinopril |
| carvedilol | Experimental | carvedilol controlled release formulation Receives: Drug: carvedilol controlled release formulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Baseline, Week 6
Secondary outcomes (10)
Change From Baseline to Week 6 in 24 Hour Mean Systolic 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 systolic blood pressure (SBP).
Measured: Baseline, Week 6
Change From Baseline to Week 6 in Trough Systolic Blood Pressure
Trough ABPM was the average across 20-24 hr after dosing for each subject.
Measured: Baseline, Week 6
Dose-response Treatment Estimates: Change From Baseline to Week 6 in 24 Hour Mean DBP by ABPM (Ambulatory Blood Pressure Monitoring)
Evaluation of the dose-response relationship between incremental doses of carvedilol CR and lisinopril and mean 24-hr ABPM DBP.
Measured: Baseline, Week 6
Change From Baseline to Week 6 in Trough to Peak Ratios of DBP by 24 Hour ABPM (Ambulatory Blood Pressure Monitoring)
Trough (20-24 hr) to peak (3-7 hr) ratios of DBP were examined in order to evaluate the extent to which once-daily criteria were met (ie trough:peak > 50%). Trough to peak ratios were calculated from change trough mean/change peak mean x 100.
Measured: Baseline, Week 6
Overall Description of Safety in Each Treatment Group Using Adverse Events, Laboratory Evaluations, ECG Changes, Vital Sign Changes, and Withdrawal Rates.
Refer to Adverse Event section for safety information.
Measured: Weeks 1 through 48
Change From Baseline to Week 6 in Mean SBP and DBP Measured in Morning by 24 Hour ABPM
Mean changes from Baseline to Week 6 in DBP and SBP measured by 24hr ABPM at the end of up-titration recorded in the morning. The morning assessment period started at or after 6 am and ended immediately before 12 noon.
Measured: Morning BP, Baseline, Week 6
Change From Baseline to Week 6 in Mean SBP and DBP Measured in Afternoon by 24hr ABPM
Mean changes from Baseline to Week 6 in SBP and DBP measured by 24hr ABPM at the end of up-titration recorded in the afternoon. The afternoon assessment period started at or after 12 noon and ended immediately before 6 pm.
Measured: Afternoon BP, Baseline, Week 6
Change From Baseline to Week 6 in Mean SBP and DBP Measured at Night by 24hr ABPM
Mean changes from Baseline to Week 6 in DBP and SBP measured by 24hr ABPM at the end of up-titration recorded in the night. The night-time assessment period started at the time of the first reading at or after 6 pm and ended immediately before 6 am on the following day.
Measured: Night BP, Baseline, Week 6
Change From Baseline to Week 6 in Mean Trough Sitting SBP and Sitting DBP by Cuff Assessment
Analysis of Change from Baseline to Week 6 in Mean sSBP and sDBP by Cuff Assessments at Drug Trough (20-24 hr) at End of Treatment Titration
Measured: Baseline, Week 6
Diastolic Responders, Defined as ≥ 10 mmHg Sitting (s)DBP Reduction From Baseline or a sDBP of <90 / 80 Millimeters (mm) of Mercury (Hg) for Non Diabetic / Diabetic Subjects Respectively (Based on Cuff Trough Measures)
Measured: Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jul 2006 (estimated)
- Study startJul 2006
- Primary completionApr 2008
- Study completionApr 2008
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 HypertensionStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 654 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00347360
- Sponsor's protocol ID
- CFD105453
- Status last verified
- Nov 2016
- First submitted
- 29 Jun 2006
- Last updated
- 26 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
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.
PubMed 20883227
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00347360
- Acronym / sponsor ID
- CFD105453
- Conditions
- Hypertension
- Keywords
- carvedilol, hypertension, lisinopril, factorial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 654 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jul 2006
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 4 Jul 2006 (estimated)
- Results
- Posted 9 Nov 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| lisinopril | Experimental | Drug: lisinoprillisinopril |
| carvedilol | Experimental | Drug: carvedilol controlled release formulationcarvedilol controlled release formulation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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].
Key exclusion criteria (24 listed)
- 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.
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 |
|---|---|---|
| lisinopril | Drug | lisinopril |
| carvedilol controlled release formulationAlso: lisinopril | Drug | carvedilol |
Primary outcome
Change From Baseline to Week 6 in 24 Hour (hr) Mean Diastolic Blood Pressure
Time frame: Baseline, Week 6.
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).
Change From Baseline to Week 6 in Trough Diastolic Blood Pressure
Time frame: Baseline, Week 6
Trough ABPM was the average across 20-24 hr after dosing for each subject.
10 secondary outcomes
Change From Baseline to Week 6 in 24 Hour Mean Systolic Blood Pressure
Time frame: Baseline, Week 6
Change From Baseline to Week 6 in Trough Systolic Blood Pressure
Time frame: Baseline, Week 6
Dose-response Treatment Estimates: Change From Baseline to Week 6 in 24 Hour Mean DBP by ABPM (Ambulatory Blood Pressure Monitoring)
Time frame: Baseline, Week 6
Change From Baseline to Week 6 in Trough to Peak Ratios of DBP by 24 Hour ABPM (Ambulatory Blood Pressure Monitoring)
Time frame: Baseline, Week 6
Overall Description of Safety in Each Treatment Group Using Adverse Events, Laboratory Evaluations, ECG Changes, Vital Sign Changes, and Withdrawal Rates.
Time frame: Weeks 1 through 48
Change From Baseline to Week 6 in Mean SBP and DBP Measured in Morning by 24 Hour ABPM
Time frame: Morning BP, Baseline, Week 6
Change From Baseline to Week 6 in Mean SBP and DBP Measured in Afternoon by 24hr ABPM
Time frame: Afternoon BP, Baseline, Week 6
Change From Baseline to Week 6 in Mean SBP and DBP Measured at Night by 24hr ABPM
Time frame: Night BP, Baseline, Week 6
Change From Baseline to Week 6 in Mean Trough Sitting SBP and Sitting DBP by Cuff Assessment
Time frame: Baseline, Week 6
Diastolic Responders, Defined as ≥ 10 mmHg Sitting (s)DBP Reduction From Baseline or a sDBP of <90 / 80 Millimeters (mm) of Mercury (Hg) for Non Diabetic / Diabetic Subjects Respectively (Based on Cuff Trough Measures)
Time frame: Week 6
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20883227Bakris 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.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
151 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing lisinopril in people with Hypertension, run by GlaxoSmithKline at 151 sites in United States.
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 14 inclusion and 24 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 26 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 151 sites in United States. 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 9 Nov 2009). 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 to Week 6 in 24 Hour (hr) Mean Diastolic Blood Pressure (time frame: Baseline, Week 6.). The study lists 2 primary outcomes in all. 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 NCT00347360, 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 26 Dec 2016.