The Vascular Effects of Carvedilol Controlled Release (CR) in Abdominally Obese Hypertensive Patients

November 13, 2013 updated by: Aaron S. Kelly, Ph.D., St. Paul Heart Clinic

The Vascular Effects of Carvedilol Controlle Release (CR) + Lisinopril Versus Lisinopril + Hydrochlorothiazide (HCTZ) in Abdominally Obese Hypertensive Patients

The purpose of this study is to compare the effects of two different combination therapies for high blood pressure on vascular health.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hydrochlorothiazide (HCTZ) has been a popular choice for the treatment of hypertension mainly due to its efficacy in lowering blood pressure, safety, and cost-effectiveness. Similarly, angiotensin converting enzyme inhibitors (ACE-I), because of their neutral to positive impact on glycemic control, have been a popular choice for addressing hypertension in abdominally obese patients. Furthermore, the ACE-I drug class has been shown to improve vascular endothelial function and inflammation in addition to its blood pressure lowering effects.

Conversely, beta-adrenergic receptor blockers (b-blockers) have generally been avoided as first line anti-hypertensive therapy in pre-diabetic patients due to concerns about worsening glycemic control and potential hastening of progression to type 2 diabetes mellitus (T2DM). However, recent data have shown that the 3rd generation b-blocker carvedilol does not negatively affect glucose metabolism and therefore may be a safe and effective choice for blood pressure control in these patients. This neutral glycemic effect is likely due to the fact that carvedilol is a non-selective b-receptor antagonist (blocks both b1 and b2 receptors) with alpha1-receptor blocking properties. In addition, carvedilol possesses anti-oxidant properties and improves endothelial function, potentially making it an attractive anti-hypertensive treatment strategy in patients with abdominal obesity.

The combination of carvedilol and lisinopril may be especially effective in reducing blood pressure and may act synergistically to address the impaired vascular function and increased inflammation and oxidative stress present in patients with the metabolic syndrome phenotype. Therefore the primary objective of the current study will be to evaluate the effects of carvedilol CR + lisinopril compared to lisinopril + HCTZ on vascular function in a head to head trial in abdominally obese, hypertensive patients. The secondary objective will be to compare the effects of these two anti-hypertensive therapies on plasma biomarkers of endothelial activation, inflammation, and oxidative stress in these patients.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • St. Paul, Minnesota, United States, 55102
        • St. Paul Heart Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • >18 years old
  • Systolic blood pressure (SBP) >130 and/or diastolic blood pressure (DBP) >85 (or currently taking anti-hypertensive medication)
  • Waist circumference >102 cm (men) and >88 cm (women)
  • Stable cardiovascular medication regimen (or other medications known to affect endothelial function) at least 1 month prior to enrollment and throughout the study

Exclusion Criteria:

  • Use of anti-hypertensive medications within one month of randomization (patients may be washed-out from anti-hypertensive medications)
  • Unstable angina
  • History of angina symptoms within 3 months of screening
  • Decompensated heart failure
  • History of myocardial infarction
  • Stroke or coronary artery bypass graft within 3 months of screening
  • Standard clinical contraindications to beta-blocker therapy
  • Standard clinical contraindications to ACE-I therapy
  • Women who are currently pregnant or planning to become pregnant (pregnancy testing will occur at specific intervals throughout study and women will be informed of potential risks during the consenting process; information specific to this risk will be detailed in the consent form)
  • Breastfeeding women
  • Clinically significant liver disease
  • Creatinine > 2.5 mg/dL
  • Hepatic function greater than 3 times upper limit of normal

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Carvediolol CR + Lisinopril, then Lisinopril + HCTZ
Subjects were randomly assigned to Carvedilol CR + Lisinopril for three months, then had a washout period of one month, and then were given Lisinopril + HCTZ for the final three months.
Drug: Carvedilol CR + Lisinopril
Participants were given Carvedilol CR + Lisinopril for three months. Oral medication. Carvedilol CR and Lisinopril combination therapy was initiated at 20 mg and 10 mg, respectively. Patients returned one week later and doses of carvedilol CR and lisinopril were increased to 40 mg and 20 mg, respectively, depending on blood pressure.
Other Names:
  • Prinivil
  • Coreg
Drug: Lisinopril + HCTZ
Participants were given Lisinopril + HCTZ for three months. Oral medication. Lisinopril + HCTZ combination therapy was initiated at 12.5 mg and 10 mg, respectively. Patients returned 1 week later and doses of hydrochlorothiazide and lisinopril were increased to 25 mg and 20 mg, respectively, depending on blood pressure levels.
Other Names:
  • Prinivil
  • Hydrochlorothiazide
ACTIVE_COMPARATOR: Lisinopril + HCTZ, then Carvedilol CR + Lisinopril
Subjects were randomally assigned to Lisinopril + HCTZ for three months, then had a washout period for one month, and then were given Carvedilol CR + Lisinopril for the final three months.
Drug: Carvedilol CR + Lisinopril
Participants were given Carvedilol CR + Lisinopril for three months. Oral medication. Carvedilol CR and Lisinopril combination therapy was initiated at 20 mg and 10 mg, respectively. Patients returned one week later and doses of carvedilol CR and lisinopril were increased to 40 mg and 20 mg, respectively, depending on blood pressure.
Other Names:
  • Prinivil
  • Coreg
Drug: Lisinopril + HCTZ
Participants were given Lisinopril + HCTZ for three months. Oral medication. Lisinopril + HCTZ combination therapy was initiated at 12.5 mg and 10 mg, respectively. Patients returned 1 week later and doses of hydrochlorothiazide and lisinopril were increased to 25 mg and 20 mg, respectively, depending on blood pressure levels.
Other Names:
  • Prinivil
  • Hydrochlorothiazide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Reactive Hyperemic Index by Period (Carvedilol CR + Lisinopril vs. Lisinopril + HCTZ)
Time Frame: Change from three months to seven months
Reactive hyperemic index is a measure of endothelial function. This is measured by the ratio of post-occlusion blood volume flow versus the baseline blood volume flow. The outcome reported is the change in this ratio after the first intervention phase compared to after the second intervention phase.
Change from three months to seven months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Paul Heart Clinic

Collaborators

GlaxoSmithKline

Investigators

  • Principal Investigator: Aaron S Kelly, PhD, St. Paul Heart Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (ACTUAL)

May 1, 2010

Study Completion (ACTUAL)

May 1, 2010

Study Registration Dates

First Submitted

April 10, 2007

First Submitted That Met QC Criteria

April 10, 2007

First Posted (ESTIMATE)

April 11, 2007

Study Record Updates

Last Update Posted (ESTIMATE)

December 6, 2013

Last Update Submitted That Met QC Criteria

November 13, 2013

Last Verified

November 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPHC 2007-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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