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Proposal 645

Title of the Proposed Research

The Influence of Age, Gender, and Race on the Effects of Combination Therapy with Carvedilol plus Lisinopril Versus Lisinopril Monotherapy for Systemic Hypertension

Lead Researcher

Partha Sardar

Affiliation

New York Medical College-Metropolitan Hospital Center
Department of Medicine
New York, NY, US

Funding Source

None

Potential Conflicts of Interest

None

Data Sharing Agreement Date

14 January 2014

Lay Summary

Background:
Beta-blockers have in the past been shown to effectively reduce blood pressure in both systolic-diastolic hypertension and isolated systolic hypertension. An important question for clinicians is whether the benefit observed with beta-blockers is also achieved for other subpopulations, including women, non-Caucasians, and elderly. Use of beta blockers showed significant benefit in younger patients, however similar benefit was not reflected in elderly (Messerli FH, et al. JAMA 1998;279(23):1903-7). Several recent article reported the association between BP lowering with beta-blockers and 1 of 2 genetic polymorphisms in the ß1-adrenergic receptor gene (ADRB1): Ser49Gly and Arg389Gly, which might cause differential effects in different ethnic populations.

The beneficial role of beta-blockers as a primary medication to treat hypertension has come under question in few previous meta-analyses. However, it is observed that the included studies in these meta-analyses were mainly based on the older second-generation ß-blockers, such as atenolol and metoprolol. Carvedilol is a third-generation noncardioselective vasodilating ß-blocker which can be used as a cardioprotective agent.

The effects of carvedilol as additional drugs with ACE inhibitor on subpopulations, including women, non-Caucasians, and elderly need to be investigated.

The aims and objectives of the research:
The primary objective of the study is to compare the effects of beta-blockers (carvedilol) plus ACE inhibitor (lisinopril) versus ACE inhibitor (lisinopril) monotherapy in three main subgroups, participants with different race (white, black, others), age( >75 years and <75 years) and gender (female/male).

How the research will be conducted:
Participants with different race, age and gender will be identified from the randomized, double-blind, parallel group, multicenter study of subjects with Stage 1 or 2 essential hypertension who were not at target blood pressure (<140/90mmHg) at Baseline. The initial study was a Phase 3 Interventional trial and the participants were enrolled in 72 centers in the United States from 27 March 2008 – 06 August 2008.

Subjects were randomized to receive either carvedilol CR + lisinopril or lisinopril + placebo. Subjects were uptitrated over a 6 week period until target blood pressure (<140/90mmHg) is met.

How the findings will be interpreted and communicated:
The primary efficacy endpoint will be the comparison of the proportion of subjects with mean sitting cuff blood pressure <140/90mmHg at the end of 6 weeks of treatment in three main subgroups , according to race (white, black, others), age( >75 years and <75 years) and gender (female/male).

Secondary efficacy endpoints will be the change from baseline to Week 6 in mean sitting cuff systolic blood pressure and sitting cuff diastolic blood pressure, and the overall description of safety in each treatment group.

Study Data Provided

Study COR111096: A Randomized, Double-Blind, Active-Controlled, Parallel Group, Multicenter Study Comparing the Proportion of Subjects with Stage 1 or 2 Essential Hypertension Who Achieve Target Blood Pressure While Receiving Either COREG CR + lisinopril or lisinopril Monotherapy

Statistical Analysis Plan

This will be added after the research is published.

Publication Citation