Cardioprotective Benefits of Carvedilol-CR or Valsartan Added to Lisinopril

NCT ID: NCT00657241

Last Updated: 2022-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2010-04-30

Brief Summary

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

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 (carvedilol 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 carvedilol 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).

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

(A) ARB first, beta-blocker second

Valsartan 160 mg daily (one week) and valsartan 320 mg daily (3 weeks) followed by carvedilol CR 20 mg daily (one week) and carvedilol CR 40 mg daily (3 weeks)

Group Type: ACTIVE_COMPARATOR

Carvedilol CR

Intervention Type: DRUG

Valsartan

Intervention Type: DRUG

(B) Beta-blocker first, ARB second

carvedilol CR 20 mg daily (one week) and carvedilol CR 40 mg daily (3 weeks) followed by valsartan 160 mg daily (1 week) and valsartan 320 mg daily (3 weeks).

Group Type: ACTIVE_COMPARATOR

Carvedilol CR

Intervention Type: DRUG

Valsartan

Intervention Type: DRUG

Interventions

Carvedilol CR

Intervention Type: DRUG

Valsartan

Intervention Type: DRUG

Other Intervention Names

Coreg CR; Diovan

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

State University of New York at Buffalo

OTHER

Sponsor Role: lead

Responsible Party

JOSEPH IZZO

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph L Izzo, M.D.

Role: PRINCIPAL_INVESTIGATOR

SUNY Buffalo

Locations

Erie County Medical Center

Buffalo, New York, United States

Countries

United States

References

Izzo JL Jr, Yedlapati SH, Faheem SM, Younus U, Osmond PJ. Differences in mean and variability of heart rate and ambulatory rate-pressure product when valsartan or carvedilol is added to lisinopril. J Am Soc Hypertens. 2012 Nov-Dec;6(6):399-404. doi: 10.1016/j.jash.2012.08.007. Epub 2012 Oct 26.

Reference Type: DERIVED

PMID: 23107894 (View on PubMed)

Other Identifiers

111704

Identifier Type: -

Identifier Source: org_study_id