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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Aaron S. Kelly, Ph.D., University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier:
NCT00459056
First received: April 10, 2007
Last updated: November 13, 2013
Last verified: November 2013
  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
Drug: Lisinopril + HCTZ
Phase 3

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 Controlle Release (CR) + Lisinopril Versus Lisinopril + Hydrochlorothiazide (HCTZ) in Abdominally Obese Hypertensive Patients

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Change in Reactive Hyperemic Index by Period (Carvedilol CR + Lisinopril vs. Lisinopril + HCTZ) [ Time Frame: Change from three months to seven months ] [ Designated as safety issue: No ]
    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.


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: 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

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: Aaron S. Kelly, Ph.D., Assistant Professor, University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT00459056     History of Changes
Other Study ID Numbers: SPHC 2007-01
Study First Received: April 10, 2007
Results First Received: April 23, 2012
Last Updated: November 13, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hypertension
Obesity, Abdominal
Vascular Diseases
Cardiovascular Diseases
Obesity
Overnutrition
Nutrition Disorders
Carvedilol
Hydrochlorothiazide, lisinopril drug combination
Hydrochlorothiazide
Lisinopril
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Vasodilator Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014