- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00585091
The Development of Tolerance to α1-Adrenoceptor Blockade With Chronic Carvedilol Treatment
June 12, 2012 updated by: edward gilbert, University of Utah
There is now strong evidence from clinical trials that carvedilol therapy in heart failure is superior to therapy with metoprolol.
Not only does carvedilol have superior effects on lipid profiles, insulin sensitivity, renal blood flow, and reversal of pathologic remodeling but also its use is associated with fewer deaths compared to metoprolol.
These facts make it important to carefully define how metoprolol and carvedilol are pharmacologically different.
One potential difference is α1-AR antagonism.
If we demonstrate that these α1-AR effects are preserved with chronic therapy, then α1-AR blockade may have an important role in carvedilol favorably altering the natural history of heart failure.
On the other hand, if we demonstrate that tolerance to the α1-AR blockade effect of carvedilol decreases with time, then it would be unlikely that this pharmacologic property contributes to the efficacy of carvedilol.
In such a case other pharmacologic properties, such as antioxidant activity, would appear to be important.
These results will help guide future studies into CHF and AR blockade.
Study Overview
Study Type
Interventional
Enrollment (Actual)
15
Phase
- Not Applicable
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
-
-
Utah
-
Salt Lake City, Utah, United States, 84112
- University of Utah
-
-
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 to 85 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Age of 18 to 85 years
- Symptomatic heart failure, NYHA class I to III
- Left ventricular ejection fraction < 0.40
- Give written informed consent
Exclusion Criteria:
- active myocarditis
- congenital heart disease
- uncorrected, hemodynamically significant stenotic valvular disease
- hypertrophic cardiomyopathy
- Asthma or other obstructive airway diseases requiring bronchodilators
- Heart rate < 60 beats/min, supine systolic blood pressure < 85 mm Hg, supine diastolic blood pressure > 90 mm Hg
- Uncontrolled Hypertension (Systolic BP >140 mmHg, Diastolic BP > 90 mmHg).
- Sick sinus syndrome, Mobitz type 2 second degree AV block or third degree AV block unless controlled with an artificial implantable pacemaker
- NYHA functional class IV symptoms
- Treatment with an excluded medication (see Excluded Medications below)
- Myocardial infarction or coronary artery intervention (CABG or angioplasty) within three months
- Unstable angina pectoris
- Presence of any progressive systemic disease that would be expected to impact the patient's outcome over the time course of the study
- Uncorrected endocrine disorders including primary aldosteronism, pheochromocytoma, hyperthyroidism, hypothyroidism, brittle type 1 diabetes mellitus
- Evidence of significant renal disease (serum creatinine > 2.5 mg/dl), or hepatic disease (transaminase level > three fold higher than laboratory normal)
- Symptomatic peripheral vascular disease
- Inability or unwillingness to cooperate with study or give written informed consent
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: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: A
All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment.
|
All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The primary objective of this study is to determine if tolerance to α1-AR blockade develops with the chronic administration of carvedilol in heart failure patients.
Time Frame: Oct 2003-Aug 2008
|
Oct 2003-Aug 2008
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment.
Time Frame: Oct 2003-Aug 2008
|
Oct 2003-Aug 2008
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Mark Munger, PharmD, Professor, Pharmacotherapy
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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
October 1, 2003
Primary Completion (Actual)
August 1, 2007
Study Completion (Actual)
August 1, 2008
Study Registration Dates
First Submitted
December 26, 2007
First Submitted That Met QC Criteria
January 2, 2008
First Posted (Estimate)
January 3, 2008
Study Record Updates
Last Update Posted (Estimate)
June 13, 2012
Last Update Submitted That Met QC Criteria
June 12, 2012
Last Verified
June 1, 2012
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Heart Failure
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Protective Agents
- Adrenergic alpha-Agonists
- Adrenergic Agonists
- Cardiotonic Agents
- Respiratory System Agents
- Sympathomimetics
- Vasoconstrictor Agents
- Mydriatics
- Nasal Decongestants
- Adrenergic alpha-1 Receptor Agonists
- Phenylephrine
- Oxymetazoline
Other Study ID Numbers
- 00011909
- IRB# 00011909
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
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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