Cardioprotective Benefits of Carvedilol-CR or Valsartan Added to Lisinopril - Full Text View

Sponsor:	State University of New York at Buffalo
Collaborator:	GlaxoSmithKline
Information provided by:	State University of New York at Buffalo
ClinicalTrials.gov Identifier:	NCT00657241

Purpose

14-week single blind, double baseline, forced-titration, cross-over comparison of the cardiac benefits of Coreg CR compared to valsartan added to existing ACE inhibition

Condition	Intervention	Phase
Hypertension	Drug: carvedilol Drug: valsartan	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Subject), Active Control, Crossover Assignment, Pharmacodynamics Study
Official Title:	Cardioprotective Benefits of Carvedilol-CR or Valsartan Added to Lisinopril

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Carvedilol Lisinopril Valsartan

U.S. FDA Resources

Further study details as provided by State University of New York at Buffalo:

Primary Outcome Measures:

Difference in resting CTTI (cardiac work) between Coreg and valsartan. [ Time Frame: 3 weeks, 6 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	April 2008
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	April 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Active Comparator Valsartan 160 mg (one week); valsartan 320 mg (3 weeks)	Drug: valsartan Valsartan 160 mg (one week); valsartan 320 mg (3 weeks)
B: Active Comparator Coreg CR 20 mg (one week) and Coreg CR 40 mg (3 weeks).	Drug: carvedilol Coreg CR 20 mg (one week) and Coreg CR 40 mg (3 weeks).

Detailed Description:

Combination drug therapy is necessary for optimal blood pressure reduction and current guidelines mandate the concomitant use of ACE inhibitors and β-blockers in most patients at significant risk for cardiovascular disease (CVD) events. There is also continuing interest in combining angiotensin receptor blockers (ARBs) with ACE inhibitors in hypertension based on the unsubstantiated belief that "more complete" renin-angiotensin system inhibition is desirable. It is more attractive physiologically to combine a long-acting β-blocker with vasodilatory actions (Coreg CR) with an ACE inhibitor because this combination addresses more directly the two fundamental hemodynamic changes needed to reduce CVD events: lowering systolic BP (afterload) and lowering heart rate; the product of the two is a reliable surrogate for reduced cardiac work. In fact, clinical trial data suggest that there is no appreciable additional BP lowering when ARBs are added to ACE inhibitors and neither class lowers heart rate. The present proposal is designed to demonstrate the superior "cardioprotection" of Coreg CR compared to ARB (valsartan) when each is added to background ACE inhibitor therapy. Principal dependent variables include ambulatory cardiac work (24-hour mean ambulatory systolic BP x heart rate) and laboratory stress responses (central systolic time-tension indices derived from arterial tonometry pre- and post-bicycle exercise). Secondary hemodynamic variables will define changes in flow and pressure (e.g. central systolic BP and forward and reflected pressure wave estimations).

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects with residual (uncontrolled) hypertension on lisinopril monotherapy, defined as 24-hour ambulatory diastolic BP >85 mmHg.

Exclusion Criteria:

A subject meeting any of the following conditions will be excluded from the study:

History of serious adverse effects with ACE inhibitor, Coreg, or valsartan
Known or suspected causes of secondary hypertension (e.g., renovascular stenosis, primary hyperaldosteronism)
Known ischemic heart disease requiring beta-blocker therapy (includes angina, prior transmural myocardial infarction, coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty or stenting within 6 months prior to study entry).
Heart failure (NYHA Functional Class II-IV)
Obstructive valvular heart disease or obstructive hypertrophic cardiomyopathy
Presence of clinically significant ventricular or supraventricular arrhythmias (e.g. atrial fibrillation/flutter), pre-excitation syndrome, second or third degree AV block, other conduction defects necessitating the implantation of a permanent cardiac pacemaker, or sick sinus syndrome.
Chronic kidney disease (serum creatinine >2.5 within past 6 months)
Uncontrolled diabetes mellitus (i.e., a fasting blood glucose >200 mg/dL [>11.1 mmol/L] or hemoglobin A1c > 10%
History of alcohol or other drug abuse within 6 months prior to enrollment
Concomitant treatment or probable need for treatment with prohibited medications. NSAIDs, diabetes medications and other chronic meds are permitted if continued throughout study without dosage change.
Any other medical condition which renders the subject unable to complete the study or which would interfere with optimal participation in the study or produce a significant risk to the subject
Those with persistent systolic BP elevations above 179 mmHg will be discontinued from the study as will those with any significant adverse effect of medication.
Positive pregnancy test or failure to practice adequate contraception in women of child-bearing potential
Bronchospastic asthma requiring chronic steroid or inhaler therapy
Any women with child-bearing potential

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00657241

Contacts

Contact: Peter J Osmond, M.S.	716.898.5485	pjosmond@buffalo.edu
Contact: Kelley J Carozzolo	716.898.5653	kjc28@buffalo.edu

Locations

United States, New York
Erie County Medical Center
Buffalo, New York, United States, 14215

Sponsors and Collaborators

State University of New York at Buffalo

GlaxoSmithKline

Investigators

Principal Investigator:

Joseph L Izzo, M.D.

SUNY Buffalo

More Information

No publications provided

Responsible Party:	SUNY Buffalo ( Joseph L. Izzo, Jr., M.D. )
Study ID Numbers:	111704
Study First Received:	April 9, 2008
Last Updated:	April 11, 2008
ClinicalTrials.gov Identifier:	NCT00657241 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by State University of New York at Buffalo:

cardiac work
coreg cr
valsartan
tonometry

Additional relevant MeSH terms:

Vasodilator Agents
Neurotransmitter Agents
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Lisinopril
Physiological Effects of Drugs
Vascular Diseases
Enzyme Inhibitors
Adrenergic alpha-Antagonists
Cardiovascular Agents
Antihypertensive Agents

Protective Agents
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Adrenergic beta-Antagonists
Cardiovascular Diseases
Adrenergic Antagonists
Valsartan
Hypertension
Carvedilol

ClinicalTrials.gov processed this record on February 08, 2010