Acute Decompensated Heart FailureNCT01971944
The Influence of Beta Blocker Therapy on the Hemodynamic Response to Inotrope Infusion in Patients With Acute Decompensated Heart Failure
An observational study of Acute Decompensated Heart Failure and Heart Failure, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
Purpose: To compare the hemodynamic effects of dobutamine and milrinone in hospitalized patients who are receiving Beta Blocker Participants: Patients who are admitted to the General Cardiology and Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure, who have… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Acute Decompensated Heart Failure, Heart Failure
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2010to Oct 2018
- Phase
- Observational
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who are admitted to the General Cardiology and Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure, and who are deemed by the health care team to require pulmonary artery catheter placement and inotropic therapy with either dobutamine or milrinone by continuous infusion.
Who may be able to join
- Patients ≥ 18 years of age and English-speaking who are admitted to the General Cardiology or Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure (ADHF).
- Patients deemed by the health care team to require hemodynamic monitoring with a pulmonary artery catheter and inotropic therapy. Patients receiving at least 3 doses of continued beta blocker therapy with carvedilol, metoprolol succinate, or metoprolol tartrate and patients receiving no beta blocker therapy or have missed at least 5 doses of beta-blocker therapy.
Who cannot join
- Concomitant treatment with other beta blockers, non-selective alpha blockers (e.g. terazosin, prazosin, doxazosin), non-dihydropyridine calcium antagonists, antiarrhythmic agents except for chronic stables doses of amiodarone, dofetilide or mexiletine.
- Use of inotropes or IV vasoactive agents within 7 days or at time of enrollment Patients with hemodynamically unstable arrhythmias (e.g., Systolic Blood Pressure (SBP) < 80, Heart Rate (HR) > 110), uncorrected primary valvular disease, or current mechanical support including left ventricular assist device (LVADs), Impella devices and balloon pumps
- Patients who have missed more than 1 dose of beta blocker within 72 hours of starting inotrope
- No subjects will be excluded based upon race, gender or ethnicity.
Trial locations and contacts
1 site in 1 country.
About this study
Purpose: To compare the hemodynamic effects of dobutamine and milrinone in hospitalized patients who are receiving Beta Blocker Participants: Patients who are admitted to the General Cardiology and Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure, who have maintained steady state concentrations of beta blocker therapy (carvedilol or metoprolol), and who are deemed by the health care team to require pulmonary artery catheter placement and inotropic therapy with dobutamine or milrinone by continuous infusion. Patients that are not currently receiving beta blocker therapy will be enrolled for comparative purposes; however, any patient not at steady state (on or off beta blocker therapy) will not be enrolled.
Procedures: After obtaining informed consent, patients will be assigned to the appropriate sub-study group based on beta blocker use (Study A: patients on stable doses of metoprolol and Study B: patients on stable doses of carvedilol). All patients should receive dobutamine followed by milrinone as outlined in the dosing algorithm (see inotrope dosing algorithm attached, as part of the usual standard of practice). Baseline pulmonary artery catheter hemodynamic parameters will be collected prior to administration of inotrope trial of dobutamine followed by milrinone. Hemodynamic parameters will be recorded per the dosing algorithm following initiation and dose titration. Dose titration will be determined by the health care team based upon patient response or lack thereof and tolerability. Changes in hemodynamic parameters in response to dobutamine or milrinone will be compared within study groups. Additionally, data will continue to be collected on patients receiving not beta blocker therapy for comparative purpose.
Read the detailed description
Background:
First-line management of chronic heart failure includes beta blockers and angiotensin converting enzyme (ACE) inhibitors, as these agents have been shown to have significant benefits on morbidity and mortality in large clinical trials. Therefore, a substantial number of patients with chronic heart failure are receiving chronic beta blocker therapy, most commonly metoprolol succinate and carvedilol. However, despite significant advancements in the treatment of chronic heart failure, the natural history of the disease remains progressive and many patients develop acute decompensations requiring hospitalization. In the setting of acute decompensated heart failure, the use of inotropic agents may be required for hemodynamic support. The two most widely used inotropes are dobutamine and milrinone. Dobutamine primarily acts as a beta-1 receptor agonist with some effects on beta-2 and alpha-1 receptors. Milrinone is a phosphodiesterase III inhibitor, thus inhibiting the breakdown of cyclic adenosine monophosphate. As such, milrinone works at a site that is distal to beta receptors and may be less influenced by chronic beta blocker therapy. As such, one may speculate that the presence of a beta blocker would influence the hemodynamic response to dobutamine, but to a much lesser extent to milrinone, if at all.
Two small studies have assessed the hemodynamic response to dobutamine in the presence and absence of beta blocker therapy in patients with chronic heart failure. In addition, one of these studies assessed the response to enoximone, another phosphodiesterase III inhibitor. Both studies demonstrated that metoprolol did not significantly affect the hemodynamic response to dobutamine infusion, including its effect on cardiac index, heart rate, stroke volume, and systemic vascular resistance. Conversely, carvedilol was shown to have significant inhibitory effects on cardiac index, heart rate, and stroke volume during dobutamine infusion. In addition, carvedilol appeared to increase mean arterial pressure at higher doses of dobutamine. In the setting of an enoximone infusion, metoprolol increased the cardiac index and stroke volume responses, while maintaining other hemodynamic parameters. There was no significant difference in the hemodynamic response to enoximone infusion in the presence of carvedilol.
Why This Study is Needed:
Published studies that assessed the hemodynamic response to inotropes in the presence and absence of beta blockers included less than 50 patients combined. As such, the replication of their results is warranted in order to use this data to drive changes in clinical practice. Additionally, and equally as important, no study has been published, to the best of our knowledge, which has assessed the hemodynamic response to milrinone in the presence of metoprolol. . Although enoximone is a phosphodiesterase III inhibitor and is theoretically similar to milrinone, it is not approved for use in the United States, thus making it difficult to extrapolate these findings to milrinone. Lastly, the severity of illness in patients included in current literature does not reflect individuals who will receive the most benefit from therapy i.e. patients with acute decompensated heart failure.
- Conditions
- Acute Decompensated Heart Failure, Heart Failure
- Keywords
- Beta Blocker, Inotrope
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients achieving steady state concentrations of carvedilol | Patients achieving steady state concentrations of carvedilol who receive a trial of dobutamine followed by milrinone. | |
| Patients achieving steady state concentrations of metoprolol | Patients achieving steady state concentrations of metoprolol who receive a trial of dobutamine followed by milrinone. | |
| Patients not receiving beta blocker | Patients not receiving beta blocker who receive a trial of dobutamine followed by milrinone. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Fick Cardiac Index ( Fick CI) from baseline to maximum tolerated dose of inotrope therapy
Dobutamine will be titrated every 2 hours as tolerated for a total of 3 titrations. Data will be collected over the 6 hour infusion.
Milrinone titration timeframes are dependent on renal function and as tolerated by patients. A total of 3 titrations may occur as tolerated over incremental timeframes of 4, 12, 18 and 24 hours. Data will be collected over the 12-72 hours the patient will be receiving the milrinone infusion.
Measured: baseline to maximum tolerated dose. (up to 6 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2013 (estimated)
- Study startDec 2010
- Primary completionSep 2017
- Study completionOct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Acute Decompensated Heart FailureStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jo Ellen Rodgers, PharmD, Principal investigator, UNC Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01971944
- Sponsor's protocol ID
- 11-1985
- Status last verified
- Nov 2018
- First submitted
- 18 Oct 2013
- Last updated
- 14 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Bollano E, Tang MS, Hjalmarson A, Waagstein F, Andersson B. Different responses to dobutamine in the presence of carvedilol or metoprolol in patients with chronic heart failure. Heart. 2003 Jun;89(6):621-4. doi: 10.1136/heart.89.6.621.
PubMed 12748215Metra M, Nodari S, D'Aloia A, Muneretto C, Robertson AD, Bristow MR, Dei Cas L. Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol. J Am Coll Cardiol. 2002 Oct 2;40(7):1248-58. doi: 10.1016/s0735-1097(02)02134-4.
PubMed 12383572Lowes BD, Tsvetkova T, Eichhorn EJ, Gilbert EM, Bristow MR. Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol. Int J Cardiol. 2001 Dec;81(2-3):141-9. doi: 10.1016/s0167-5273(01)00520-4.
PubMed 11744130Woolfrey SG, Hegbrant J, Thysell H, Fox PA, Lendrem DW, Lockwood GF, Lasher K, Rogers J, Greenslade D. Dose regimen adjustment for milrinone in congestive heart failure patients with moderate and severe renal failure. J Pharm Pharmacol. 1995 Aug;47(8):651-5. doi: 10.1111/j.2042-7158.1995.tb05853.x.
PubMed 8583366
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Influence of Beta Blocker Therapy on the Hemodynamic Response to Inotrope Infusion in Patients With Acute Decompensated Heart Failure
- ClinicalTrials.gov ID
- NCT01971944
- Acronym / sponsor ID
- 11-1985
- Conditions
- Acute Decompensated Heart Failure, Heart Failure
- Keywords
- Beta Blocker, Inotrope
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Study start
- Dec 2010
- Primary completion
- Sep 2017 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 30 Oct 2013 (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.
Purpose: To compare the hemodynamic effects of dobutamine and milrinone in hospitalized patients who are receiving Beta Blocker Participants: Patients who are admitted to the General Cardiology and Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure, who have maintained steady state concentrations of beta blocker therapy (carvedilol or metoprolol), and who are deemed by the health care team to require pulmonary artery catheter placement and inotropic therapy with dobutamine or milrinone by continuous infusion. Patients that are not currently receiving beta blocker therapy will be enrolled for comparative purposes; however, any patient not at steady state (on or off beta blocker therapy) will not be enrolled.
Procedures: After obtaining informed consent, patients will be assigned to the appropriate sub-study group based on beta blocker use (Study A: patients on stable doses of metoprolol and Study B: patients on stable doses of carvedilol). All patients should receive dobutamine followed by milrinone as outlined in the dosing algorithm (see inotrope dosing algorithm attached, as part of the usual standard of practice). Baseline pulmonary artery catheter hemodynamic parameters will be collected prior to administration of inotrope trial of dobutamine followed by milrinone. Hemodynamic parameters will be recorded per the dosing algorithm following initiation and dose titration. Dose titration will be determined by the health care team based upon patient response or lack thereof and tolerability. Changes in hemodynamic parameters in response to dobutamine or milrinone will be compared within study groups. Additionally, data will continue to be collected on patients receiving not beta blocker therapy for comparative purpose.
Detailed description
Background:
First-line management of chronic heart failure includes beta blockers and angiotensin converting enzyme (ACE) inhibitors, as these agents have been shown to have significant benefits on morbidity and mortality in large clinical trials. Therefore, a substantial number of patients with chronic heart failure are receiving chronic beta blocker therapy, most commonly metoprolol succinate and carvedilol. However, despite significant advancements in the treatment of chronic heart failure, the natural history of the disease remains progressive and many patients develop acute decompensations requiring hospitalization. In the setting of acute decompensated heart failure, the use of inotropic agents may be required for hemodynamic support. The two most widely used inotropes are dobutamine and milrinone. Dobutamine primarily acts as a beta-1 receptor agonist with some effects on beta-2 and alpha-1 receptors. Milrinone is a phosphodiesterase III inhibitor, thus inhibiting the breakdown of cyclic adenosine monophosphate. As such, milrinone works at a site that is distal to beta receptors and may be less influenced by chronic beta blocker therapy. As such, one may speculate that the presence of a beta blocker would influence the hemodynamic response to dobutamine, but to a much lesser extent to milrinone, if at all.
Two small studies have assessed the hemodynamic response to dobutamine in the presence and absence of beta blocker therapy in patients with chronic heart failure. In addition, one of these studies assessed the response to enoximone, another phosphodiesterase III inhibitor. Both studies demonstrated that metoprolol did not significantly affect the hemodynamic response to dobutamine infusion, including its effect on cardiac index, heart rate, stroke volume, and systemic vascular resistance. Conversely, carvedilol was shown to have significant inhibitory effects on cardiac index, heart rate, and stroke volume during dobutamine infusion. In addition, carvedilol appeared to increase mean arterial pressure at higher doses of dobutamine. In the setting of an enoximone infusion, metoprolol increased the cardiac index and stroke volume responses, while maintaining other hemodynamic parameters. There was no significant difference in the hemodynamic response to enoximone infusion in the presence of carvedilol.
Why This Study is Needed:
Published studies that assessed the hemodynamic response to inotropes in the presence and absence of beta blockers included less than 50 patients combined. As such, the replication of their results is warranted in order to use this data to drive changes in clinical practice. Additionally, and equally as important, no study has been published, to the best of our knowledge, which has assessed the hemodynamic response to milrinone in the presence of metoprolol. . Although enoximone is a phosphodiesterase III inhibitor and is theoretically similar to milrinone, it is not approved for use in the United States, thus making it difficult to extrapolate these findings to milrinone. Lastly, the severity of illness in patients included in current literature does not reflect individuals who will receive the most benefit from therapy i.e. patients with acute decompensated heart failure.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients achieving steady state concentrations of carvedilol | – | –Patients achieving steady state concentrations of carvedilol who receive a trial of dobutamine followed by milrinone. |
| Patients achieving steady state concentrations of metoprolol | – | –Patients achieving steady state concentrations of metoprolol who receive a trial of dobutamine followed by milrinone. |
| Patients not receiving beta blocker | – | –Patients not receiving beta blocker who receive a trial of dobutamine followed by milrinone. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who are admitted to the General Cardiology and Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure, and who are deemed by the health care team to require pulmonary artery catheter placement and inotropic therapy with either dobutamine or milrinone by continuous infusion.
Key inclusion criteria (2 listed)
- Patients ≥ 18 years of age and English-speaking who are admitted to the General Cardiology or Heart Failure Services at the University of North Carolina Hospitals with acute decompensated heart failure (ADHF).
- Patients deemed by the health care team to require hemodynamic monitoring with a pulmonary artery catheter and inotropic therapy. Patients receiving at least 3 doses of continued beta blocker therapy with carvedilol, metoprolol succinate, or metoprolol tartrate and patients receiving no beta blocker therapy or have missed at least 5 doses of beta-blocker therapy.
Key exclusion criteria (4 listed)
- Concomitant treatment with other beta blockers, non-selective alpha blockers (e.g. terazosin, prazosin, doxazosin), non-dihydropyridine calcium antagonists, antiarrhythmic agents except for chronic stables doses of amiodarone, dofetilide or mexiletine.
- Use of inotropes or IV vasoactive agents within 7 days or at time of enrollment Patients with hemodynamically unstable arrhythmias (e.g., Systolic Blood Pressure (SBP) < 80, Heart Rate (HR) > 110), uncorrected primary valvular disease, or current mechanical support including left ventricular assist device (LVADs), Impella devices and balloon pumps
- Patients who have missed more than 1 dose of beta blocker within 72 hours of starting inotrope
- No subjects will be excluded based upon race, gender or ethnicity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change in Fick Cardiac Index ( Fick CI) from baseline to maximum tolerated dose of inotrope therapy
Time frame: baseline to maximum tolerated dose. (up to 6 hours)
Dobutamine will be titrated every 2 hours as tolerated for a total of 3 titrations. Data will be collected over the 6 hour infusion. Milrinone titration timeframes are dependent on renal function and as tolerated by patients. A total of 3 titrations may occur as tolerated over incremental timeframes of 4, 12, 18 and 24 hours. Data will be collected over the 12-72 hours the patient will be receiving the milrinone infusion.
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 14 Nov 2018.
- Background: PubMed 12748215Bollano E, Tang MS, Hjalmarson A, Waagstein F, Andersson B. Different responses to dobutamine in the presence of carvedilol or metoprolol in patients with chronic heart failure. Heart. 2003 Jun;89(6):621-4. doi: 10.1136/heart.89.6.621.
- Background: PubMed 12383572Metra M, Nodari S, D'Aloia A, Muneretto C, Robertson AD, Bristow MR, Dei Cas L. Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol. J Am Coll Cardiol. 2002 Oct 2;40(7):1248-58. doi: 10.1016/s0735-1097(02)02134-4.
- Background: PubMed 11744130Lowes BD, Tsvetkova T, Eichhorn EJ, Gilbert EM, Bristow MR. Milrinone versus dobutamine in heart failure subjects treated chronically with carvedilol. Int J Cardiol. 2001 Dec;81(2-3):141-9. doi: 10.1016/s0167-5273(01)00520-4.
- Background: PubMed 8583366Woolfrey SG, Hegbrant J, Thysell H, Fox PA, Lendrem DW, Lockwood GF, Lasher K, Rogers J, Greenslade D. Dose regimen adjustment for milrinone in congestive heart failure patients with moderate and severe renal failure. J Pharm Pharmacol. 1995 Aug;47(8):651-5. doi: 10.1111/j.2042-7158.1995.tb05853.x.
Related trials for Acute Decompensated Heart Failure
Not yet recruitingPhase 3
Early Discharge With Subcutaneous Furosemide Versus Standard Care in Acute Heart Failure
Heart Failure, Acute Decompensated Heart Failure
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
RecruitingPhase 3
Effects of Continued Administration of Empagliflozin in Patients With Heart Failure on Active SGLT2 Inhibitor Treatment Admitted for Acute Decompensated Heart Failure
Acute Decompensated Heart Failure (ADHF)
Recruiting
Low Level Tragus Stimulation in Acute Decompensated Heart Failure
Acute Decompensated Heart Failure
Recruiting
Fluid Management of Acute Decompensated Heart Failure Subjects Treated With Reprieve System (FASTR-II) (IDE-G210258)
Acute Decompensated Heart Failure
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.
Jo Ellen Rodgers, PharmD principal investigator
UNC Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Decompensated Heart Failure and Heart Failure, run by University of North Carolina, Chapel Hill 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 2 inclusion and 4 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 14 Nov 2018. 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?
Change in Fick Cardiac Index ( Fick CI) from baseline to maximum tolerated dose of inotrope therapy (time frame: baseline to maximum tolerated dose. (up to 6 hours)). 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 NCT01971944, which also lists 4 linked publications.
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 14 Nov 2018.