The Vascular Effects of Carvedilol CR Plus Lisinopril Versus Lisinopril Plus Hydrochlorothiazide in Abdominally Obese Hypertensive Patients - Full Text View

Sponsor:	St. Paul Heart Clinic
Collaborator:	GlaxoSmithKline
Information provided by:	St. Paul Heart Clinic
ClinicalTrials.gov Identifier:	NCT00459056

Purpose

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

Condition	Intervention	Phase
Abdominal Obesity Hypertension	Drug: carvedilol cr, lisinopril, hydrochlorothiazide Drug: carvedilol CR + lisinopril	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	The Vascular Effects of Carvedilol CR + Lisinopril Versus Lisinopril + Hydrochlorothiazide in Abdominally Obese Hypertensive Patients

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure Obesity

Drug Information available for: Hydrochlorothiazide Carvedilol Lisinopril

U.S. FDA Resources

Further study details as provided by St. Paul Heart Clinic:

Primary Outcome Measures:

Vascular endothelial function [ Time Frame: 7 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Biomarkers of endothelial activation, inflammation, and oxidative stress [ Time Frame: 7 months ] [ Designated as safety issue: No ]

Enrollment:	25
Study Start Date:	April 2007
Study Completion Date:	May 2010
Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 carvedilol CR + lisinopril	Drug: carvedilol CR + lisinopril oral tablet with varying doses based upon blood pressure response
Active Comparator: 2 lisinopril + HCTZ	Drug: carvedilol cr, lisinopril, hydrochlorothiazide oral tablets of varying doses based upon blood pressure response

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 a1-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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

>18 years old
SBP >130 and/or 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 b-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: ALT

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00459056

Locations

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

Sponsors and Collaborators

St. Paul Heart Clinic

GlaxoSmithKline

Investigators

Principal Investigator:

Aaron S Kelly, PhD

St. Paul Heart Clinic

More Information

No publications provided

Responsible Party:	St. Paul Heart Clinic
ClinicalTrials.gov Identifier:	NCT00459056 History of Changes
Other Study ID Numbers:	SPHC 2007-01
Study First Received:	April 10, 2007
Last Updated:	July 19, 2011
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:

Hypertension
Obesity
Obesity, Abdominal
Vascular Diseases
Cardiovascular Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Hydrochlorothiazide
Carvedilol
Hydrochlorothiazide, lisinopril drug combination
Lisinopril
Diuretics

Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists

ClinicalTrials.gov processed this record on February 13, 2012