The Vascular Effects of Carvedilol CR + Lisinopril Versus Lisinopril + Hydrochlorothiazide in Abdominally Obese Hypertensive Patients
Information source: St. Paul Heart Clinic
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Abdominal Obesity; Hypertension
Intervention: carvedilol cr, lisinopril, hydrochlorothiazide (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: St. Paul Heart Clinic Official(s) and/or principal investigator(s):
Aaron S Kelly, PhD, Principal Investigator, Affiliation: St. Paul Heart Clinic
Summary
The purpose of this study is to compare the effects of two different combination therapies
for high blood pressure on vascular health.
Clinical Details
Official title: The Vascular Effects of Carvedilol CR + Lisinopril Versus Lisinopril + Hydrochlorothiazide in Abdominally Obese Hypertensive Patients
Study design: Treatment, Randomized, Double-Blind, Active Control, Crossover Assignment, Efficacy Study
Primary outcome: Vascular endothelial function
Secondary outcome: Biomarkers of endothelial activation, inflammation, and oxidative stress
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
St. Paul Heart Clinic, St. Paul, Minnesota 55102, United States; Recruiting
Aaron S Kelly, PhD, Phone: 651-726-6963, Email: kelly105@umn.edu
Tamara O'Black, Phone: 651-726-2716, Email: toblack@stphc.com
Aaron S Kelly, PhD, Principal Investigator
Additional Information
Starting date: April 2007
Last updated: April 10, 2007
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