Heart FailureNCT00585091
The Development of Tolerance to α1-Adrenoceptor Blockade With Chronic Carvedilol Treatment
A study testing phenylephrine in people with Heart Failure, run by University of Utah at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- phenylephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2003to Aug 2008
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age of 18 to 85 years
- Symptomatic heart failure, NYHA class I to III
- Left ventricular ejection fraction < 0.40
- Give written informed consent
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Heart Failure
- Being tested
- phenylephrine
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
phenylephrineDrug
All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment.
| Study group | Role | What they receive |
|---|---|---|
| A | Other | All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment. Receives: Drug: phenylephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Oct 2003-Aug 2008
Secondary outcomes (1)
All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment.
Measured: Oct 2003-Aug 2008
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2008 (estimated)
- Study startOct 2003
- Primary completionAug 2007
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, edward gilbert, University of Utah
- Investigators
- Mark Munger, PharmD, Principal investigator, Professor, Pharmacotherapy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00585091
- Sponsor's protocol ID
- 00011909
- Other IDs
- IRB# 00011909
- Status last verified
- Jun 2012
- First submitted
- 26 Dec 2007
- Last updated
- 13 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Van Tassell BW, Rondina MT, Huggins F, Gilbert EM, Munger MA. Carvedilol increases blood pressure response to phenylephrine infusion in heart failure subjects with systolic dysfunction: evidence of improved vascular alpha1-adrenoreceptor signal transduction. Am Heart J. 2008 Aug;156(2):315-21. doi: 10.1016/j.ahj.2008.04.004. Epub 2008 Jun 20.
PubMed 18657662
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Development of Tolerance to α1-Adrenoceptor Blockade With Chronic Carvedilol Treatment
- ClinicalTrials.gov ID
- NCT00585091
- Acronym / sponsor ID
- 00011909
- Conditions
- Heart Failure
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Oct 2003
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 3 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Other | Drug: phenylephrineAll patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age of 18 to 85 years
- Symptomatic heart failure, NYHA class I to III
- Left ventricular ejection fraction < 0.40
- Give written informed consent
Key exclusion criteria (17 listed)
- active myocarditis
- congenital heart disease
- uncorrected, hemodynamically significant stenotic valvular disease
- hypertrophic cardiomyopathy
- Asthma or other obstructive airway diseases requiring bronchodilators
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| phenylephrineAll patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment. | Drug | A |
Primary outcome
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
1 secondary outcome
All patients undergo repeated phenylephrine infusions during standard up-titration and maintenance of carvedilol treatment.
Time frame: Oct 2003-Aug 2008
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2012.
- Results publication: PubMed 18657662Van Tassell BW, Rondina MT, Huggins F, Gilbert EM, Munger MA. Carvedilol increases blood pressure response to phenylephrine infusion in heart failure subjects with systolic dysfunction: evidence of improved vascular alpha1-adrenoreceptor signal transduction. Am Heart J. 2008 Aug;156(2):315-21. doi: 10.1016/j.ahj.2008.04.004. Epub 2008 Jun 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Munger, PharmD principal investigator
Professor, Pharmacotherapy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing phenylephrine in people with Heart Failure, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00585091, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2012.